@article{SchuhmannPappStolletal.2021,
  author    = {Schuhmann, Michael K. and Papp, Lena and Stoll, Guido and Blum, Robert and Volkmann, Jens and Fluri, Felix},
  title     = {Mesencephalic electrical stimulation reduces neuroinflammation after photothrombotic stroke in rats by targeting the cholinergic anti-inflammatory pathway},
  series = {International Journal of Molecular Sciences},
  volume    = {22},
  journal   = {International Journal of Molecular Sciences},
  number    = {3},
  issn      = {1422-0067},
  doi       = {10.3390/ijms22031254},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259099},
  year      = {2021},
  abstract  = {Inflammation is crucial in the pathophysiology of stroke and thus a promising therapeutic target. High-frequency stimulation (HFS) of the mesencephalic locomotor region (MLR) reduces perilesional inflammation after photothrombotic stroke (PTS). However, the underlying mechanism is not completely understood. Since distinct neural and immune cells respond to electrical stimulation by releasing acetylcholine, we hypothesize that HFS might trigger the cholinergic anti-inflammatory pathway via activation of the α7 nicotinic acetylcholine receptor (α7nAchR). To test this hypothesis, rats underwent PTS and implantation of a microelectrode into the MLR. Three hours after intervention, either HFS or sham-stimulation of the MLR was applied for 24 h. IFN-γ, TNF-α, and IL-1α were quantified by cytometric bead array. Choline acetyltransferase (ChAT)\(^+\) CD4\(^+\)-cells and α7nAchR\(^+\)-cells were quantified visually using immunohistochemistry. Phosphorylation of NFĸB, ERK1/2, Akt, and Stat3 was determined by Western blot analyses. IFN-γ, TNF-α, and IL-1α were decreased in the perilesional area of stimulated rats compared to controls. The number of ChAT\(^+\) CD4\(^+\)-cells increased after MLR-HFS, whereas the amount of α7nAchR\(^+\)-cells was similar in both groups. Phospho-ERK1/2 was reduced significantly in stimulated rats. The present study suggests that MLR-HFS may trigger anti-inflammatory processes within the perilesional area by modulating the cholinergic system, probably via activation of the α7nAchR.},
  language  = {en}
}
@phdthesis{Greeske2008,
  author    = {Greeske, Juliane},
  title     = {Mechanismen der Makrophagen-Aktivierung in Connexin32-defizienten M{\"a}usen},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-27491},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2008},
  abstract  = {Connexin32- defiziente M{\"a}use stellen ein Mausmodell f{\"u}r eine Form der heredit{\"a}ren peripheren Neuropahtie dar. Es konnte gezeigt werden, dass Makrophagen, m{\"o}glicherweise aktiviert durch MCP-1, die Demyelinisierung in Connexin32-defizienten M{\"a}usen vermitteln. Diese Arbeit untersucht m{\"o}gliche Signaltransduktionswege, die in den peripheren Nerven Connexin32- defizienter M{\"a}use aktiviert sein k{\"o}nnten und damit in Zusammenhang mit der Genexpression von MCP-1 und/oder Makrophagen-Aktivierung stehen k{\"o}nnten.},
  subject      = {Makrophage},
  language  = {de}
}
@article{DipaolaPavanCattaneoetal.2016,
  author    = {Dipaola, Mariangela and Pavan, Esteban E. and Cattaneo, Andrea and Frazzitta, Giuseppe and Pezzoli, Gianni and Cavallari, Paolo and Frigo, Carlo A. and Isaias, Ioannis U.},
  title     = {Mechanical Energy Recovery during Walking in Patients with Parkinson Disease},
  series = {PLoS ONE},
  volume    = {11},
  journal   = {PLoS ONE},
  number    = {6},
  doi       = {10.1371/journal.pone.0156420},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-179739},
  year      = {2016},
  abstract  = {The mechanisms of mechanical energy recovery during gait have been thoroughly investigated in healthy subjects, but never described in patients with Parkinson disease (PD). The aim of this study was to investigate whether such mechanisms are preserved in PD patients despite an altered pattern of locomotion. We consecutively enrolled 23 PD patients (mean age 64±9 years) with bilateral symptoms (H\&Y ≥II) if able to walk unassisted in medication-off condition (overnight suspension of all dopaminergic drugs). Ten healthy subjects (mean age 62±3 years) walked both at their 'preferred' and 'slow' speeds, to match the whole range of PD velocities. Kinematic data were recorded by means of an optoelectronic motion analyzer. For each stride we computed spatio-temporal parameters, time-course and range of motion (ROM) of hip, knee and ankle joint angles. We also measured kinetic (Wk), potential (W\(_{p}\)), total (W\(_{totCM}\)) energy variations and the energy recovery index (ER). Along with PD progression, we found a significant correlation of W\(_{totCM}\) and W\(_{p}\) with knee ROM and in particular with knee extension in terminal stance phase. W\(_{k}\) and ER were instead mainly related to gait velocity. In PD subjects, the reduction of knee ROM significantly diminished both W\(_{p}\) and W\(_{totCM}\). Rehabilitation treatments should possibly integrate passive and active mobilization of knee to prevent a reduction of gait-related energetic components.},
  language  = {en}
}
@article{UeceylerBikoSommer2010,
  author    = {Ueceyler, Nurcan and Biko, Lydia and Sommer, Claudia},
  title     = {MDL-28170 Has No Analgesic Effect on CCI Induced Neuropathic Pain in Mice},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68359},
  year      = {2010},
  abstract  = {The calpain inhibitor MDL-28710 blocks the early local pro-inflammatory cytokine gene expression in mice after chronic constriction nerve injury (CCI). Onehundred- thirteen wild type mice of C57Bl/6J background received CCI of the right sciatic nerve. Mechanical paw withdrawal thresholds and thermal withdrawal latencies were investigated at baseline and at 1, 3, and 7 days after CCI. Three application regimens were used for MDL-28170: a) single injection 40 min before CCI; b) serial injections of MDL- 28170 40 min before and up to day three after CCI; c) sustained application via intraperitoneal osmotic pumps. The control animals received the vehicle DMSO/PEG 400. The tolerable dose of MDL-28170 for mice was 30 mg/kg body weight, higher doses were lethal within the first hours after application. Mechanical withdrawal thresholds and thermal withdrawal latencies were reduced after CCI and did not normalize after single or serial injections, nor with application of MDL-28170 via osmotic pumps. Although the calpain inhibitor MDL-28170 inhibits the early local cytokine upregulation in the sciatic nerve after CCI, pain behavior is not altered. This finding implies that local cytokine upregulation after nerve injury alone is only one factor in the induction and maintenance of neuropathic pain.},
  subject      = {Medizin},
  language  = {en}
}
@phdthesis{Karch2022,
  author    = {Karch, Katharina},
  title     = {Mapping and Neutralization of Antibodies against Neurofascin, Contactin 1, Contactin associated protein 1 and Cortactin},
  doi       = {10.25972/OPUS-28022},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-280223},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Immune-mediated polyneuropathies like chronic inflammatory demyelinating polyradiculoneuropathy or Guillain-Barr{\´e} syndrome are rare diseases of the peripheral nervous system. A subgroup of patients harbors autoantibodies against nodal or paranodal antigens, associated with a distinct phenotype and treatment response. In a part of patients with pathologic paranodal or nodal immunoreactivity the autoantigens remain difficult or impossible to determine owing to limitations of the used detection approach - usually ELISAs (enzyme-linked-immunosorbent-assays) - and incomplete knowledge of the possible autoantigens. Due to their high-throughput, low sample consumption and high sensitivity as well as the possibility to display many putative nodal and paranodal autoantigens simultaneously, peptide microarray-based approaches are prime candidates for the discovery of novel autoantigens, point-of-care diagnostics and, in addition, monitoring of pathologic autoimmune response. Current applications of peptide microarrays are however limited by high false-positive rates and the associated need for detailed follow-up studies and validation. Here, robust peptide microarray-based detection of antibodies and the efficient validation of binding signals by on-chip neutralization is demonstrated. First, autoantigens were displayed as overlapping peptide libraries in microarray format. Copies of the biochips were used for the fine mapping of antibody epitopes. Next, binding signals were validated by antibody neutralization in solution. Since neutralizing peptides are obtained in the process of microarray fabrications, neither throughput nor costs are significantly altered. Similar in-situ validation approaches could contribute to future autoantibody characterization and detection methods as well as to therapeutic research. Areas of application could be expanded to any autoimmune-mediated neurological disease as a long-term vision.},
  subject      = {Microarray},
  language  = {en}
}
@article{PohGreenAgostinellietal.2022,
  author    = {Poh, Eugenia Z. and Green, Courtney and Agostinelli, Luca and Penrose-Menz, Marissa and Karl, Ann-Kathrin and Harvey, Alan R. and Rodger, Jennifer},
  title     = {Manipulating the level of sensorimotor stimulation during LI-rTMS can improve visual circuit reorganisation in adult ephrin-A2A5\(^{-/-}\) Mice},
  series = {International Journal of Molecular Sciences},
  volume    = {23},
  journal   = {International Journal of Molecular Sciences},
  number    = {5},
  issn      = {1422-0067},
  doi       = {10.3390/ijms23052418},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284090},
  year      = {2022},
  abstract  = {Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that has the potential to treat a variety of neurologic and psychiatric disorders. The extent of rTMS-induced neuroplasticity may be dependent on a subject's brain state at the time of stimulation. Chronic low intensity rTMS (LI-rTMS) has previously been shown to induce beneficial structural and functional reorganisation within the abnormal visual circuits of ephrin-A2A5\(^{-/-}\) mice in ambient lighting. Here, we administered chronic LI-rTMS in adult ephrin-A2A5\(^{-/-}\) mice either in a dark environment or concurrently with voluntary locomotion. One day after the last stimulation session, optokinetic responses were assessed and fluorescent tracers were injected to map corticotectal and geniculocortical projections. We found that LI-rTMS in either treatment condition refined the geniculocortical map. Corticotectal projections were improved in locomotion+LI-rTMS subjects, but not in dark + LI-rTMS and sham groups. Visuomotor behaviour was not improved in any condition. Our results suggest that the beneficial reorganisation of abnormal visual circuits by rTMS can be significantly influenced by simultaneous, ambient visual input and is enhanced by concomitant physical exercise. Furthermore, the observed pathway-specific effects suggest that regional molecular changes and/or the relative proximity of terminals to the induced electric fields influence the outcomes of LI-rTMS on abnormal circuitry.},
  language  = {en}
}
@phdthesis{Weise2006,
  author    = {Weise, David Thomas},
  title     = {Maladaptive Plastizit{\"a}t bei Schreibkrampf-Patienten},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-26734},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2006},
  abstract  = {Der Schreibkrampf ist eine Form der fokalen Handdystonie, die durch anhaltende, unwillk{\"u}rliche Verkrampfung der Hand beim Schreiben gekennzeichnet ist und zu unnat{\"u}rlicher, zum Teil statischer und schmerzhafter Handhaltung f{\"u}hrt. Bei pr{\"a}disponierten Personen kann dieser nach exzessiver Wiederholung von stereotypen Bewegungen auftreten. Bewegungen und sensible Stimulation f{\"u}hren durch Mechanismen neuronaler Plastizit{\"a}t zu dynamischer Modulation sensibler und motorischer kortikaler Repr{\"a}sentationen. Wird neuronale Plastizit{\"a}t nicht in nat{\"u}rlichen Grenzen gehalten, kann es zu ver{\"a}nderten, entdifferenzierten neuronalen Repr{\"a}sentationen wie sie bei fokaler Handdystonie gefunden werden, f{\"u}hren. Zellul{\"a}re Kandidatenmechanismen f{\"u}r die Bildung neuronaler Engramme sind die Langzeitpotenzierung und -depression (LTP / LTD) neuronaler Synapsen. Wir verwendeten die als ein Modell f{\"u}r assoziative LTP und LTD beim Menschen entwickelte assoziative Paarstimulation (PAS). Mit dieser Methode untersuchten wir die zeitlichen und r{\"a}umlichen Eigenschaften neuronaler Plastizit{\"a}t des Motorkortex bei Schreibkrampf-Patienten. Eine niederfrequente elektrische Stimulation eines peripheren Nerven (N. medianus (MN) oder N. ulnaris (UN)) wurde wiederholt (0,1Hz, 180 Reizpaare) mit einer transkraniellen Magnetstimulation (TMS) {\"u}ber dem homotopen kontralateralen Motorkortex mit einem Zeitintervall von 21,5ms (MN-PAS21.5; UN-PAS21.5) oder 10ms (MN-PAS10) kombiniert. Bei MN-PAS21.5 und MN-PAS10 wurde die optimale Spulenposition so gew{\"a}hlt, dass das magnetisch evozierte motorische Potential (MEP) im kontralateralen M. abductor pollicis brevis (APB) eine maximale Gr{\"o}ße annahm, f{\"u}r UN-PAS21.5 wurde die Spule {\"u}ber dem "Hotspot" des M. abductor digiti minimi (ADM) platziert. Zehn Schreibkrampf-Patienten (Alter 39±9 Jahre; Mittelwert±Standardabweichung) und 10 gesunde bez{\"u}glich Alter und Geschlecht angepasste Probanden wurden untersucht. Ver{\"a}nderungen der Exzitabilit{\"a}t wurden mittels TMS bis zu 85 min nach der jeweiligen Intervention gemessen. Nach MN-PAS21.5 oder UN-PAS21.5 stieg die Amplitude der MEPs bei den gesunden Probanden nur in den Muskeln, die homotope externe PAS Stimulation erhalten hatten (APB Zielmuskel f{\"u}r MN; ADM f{\"u}r UN), nicht aber in Muskeln, die nicht homotop stimuliert worden waren. Im Gegensatz dazu stiegen bei Schreibkrampf-Patienten nach MN-PAS21.5 oder UN-PAS21.5 die Amplituden der APB und ADM-MEPs unabh{\"a}ngig von dem Ort der peripheren oder zentralen Stimulation. Bei Schreibkrampf-Patienten war eine fr{\"u}here, st{\"a}rkere und l{\"a}ngere Zunahme der kortikalen Exzitabilit{\"a}t im Vergleich zu den Kontrollen zu verzeichnen. Qualitativ {\"a}hnliche Beobachtungen konnten in umgekehrtem Sinne (fr{\"u}here und l{\"a}ngere Abnahme der Exzitabilit{\"a}t im homo- und heterotopen Muskel) nach MN-PAS10 gemacht werden. LTP- und LTD-{\"a}hnliche Plastizit{\"a}t ist bei Schreibkrampf-Patienten demnach gesteigert und die normale strenge topographische Spezifit{\"a}t PAS-induzierter Plastizit{\"a}t aufgehoben. Diese maladaptive Plastizit{\"a}t k{\"o}nnte ein Bindeglied zwischen repetitiven Bewegungen und gest{\"o}rter sensomotorischer Repr{\"a}sentation darstellen, damit zu einem besseren Verst{\"a}ndnis der Pathophysiologie der Dystonie beitragen und letztendlich m{\"o}gliche therapeutische Konsequenzen implizieren.},
  subject      = {Neuronale Plastizit{\"a}t},
  language  = {de}
}
@article{WeiseStoll2012,
  author    = {Weise, Gesa and Stoll, Guido},
  title     = {Magnetic resonance imaging of blood brain/nerve barrier dysfunction and leukocyte infiltration: closely related or discordant?},
  series = {Frontiers in Neurology},
  volume    = {3},
  journal   = {Frontiers in Neurology},
  number    = {178},
  doi       = {10.3389/fneur.2012.00178},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-123359},
  year      = {2012},
  abstract  = {Unlike other organs the nervous system is secluded from the rest of the organism by the blood brain barrier (BBB) or blood nerve barrier (BNB) preventing passive influx of fluids from the circulation. Similarly, leukocyte entry to the nervous system is tightly controlled. Breakdown of these barriers and cellular inflammation are hallmarks of inflammatory as well as ischemic neurological diseases and thus represent potential therapeutic targets. The spatiotemporal relationship between BBB/BNB disruption and leukocyte infiltration has been a matter of debate. We here review contrast-enhanced magnetic resonance imaging (MRI) as a non-invasive tool to depict barrier dysfunction and its relation to macrophage infiltration in the central and peripheral nervous system under pathological conditions. Novel experimental contrast agents like Gadofluorine M (Gf) allow more sensitive assessment of BBB dysfunction than conventional Gadolinium (Gd)-DTPA enhanced MRI. In addition, Gf facilitates visualization of functional and transient alterations of the BBB remote from lesions. Cellular contrast agents such as superparamagnetic iron oxide particles (SPIO) and perfluorocarbons enable assessment of leukocyte (mainly macrophage) infiltration by MR technology. Combined use of these MR contrast agents disclosed that leukocytes can enter the nervous system independent from a disturbance of the BBB, and vice versa, a dysfunctional BBB/BNB by itself is not sufficient to attract inflammatory cells from the circulation. We will illustrate these basic imaging findings in animal models of multiple sclerosis, cerebral ischemia, and traumatic nerve injury and review corresponding findings in patients.},
  language  = {en}
}
@article{KunzeLillaStetteretal.2018,
  author    = {Kunze, Ekkehard and Lilla, Nadine and Stetter, Christian and Ernestus, Ralf-Ingo and Westermaier, Thomas},
  title     = {Magnesium protects in episodes of critical perfusion after aneurysmal SAH},
  series = {Translational Neuroscience},
  volume    = {9},
  journal   = {Translational Neuroscience},
  number    = {1},
  doi       = {10.1515/tnsci-2018-0016},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177078},
  pages     = {99-105},
  year      = {2018},
  abstract  = {Background: To analyze whether magnesium has a neuroprotective effect during episodes that indicate a critical brain perfusion after aneurysmal subarachnoid hemorrhage (SAH). Methods: 107 patients with aSAH were randomized to continuously receive intravenous magnesium sulfate with target serum levels of 2.0 - 2.5 mmol/l (n = 54) or isotonic saline (n = 53). Neurological examination and transcranial Doppler sonography (TCD) were performed daily, Perfusion-CT (PCT) was acquired in 3-day intervals, angiography in case of suspected vasospasm. The primary endpoint was the development of secondary infarction following episodes of delayed ischemic neurological deficit (DIND), elevated mean flow velocity (MFV) in TCD or pathological findings in PCT. Results: In the magnesium group, 9 episodes of DIND were registered, none was followed by secondary infarction. In the control group, 23 episodes of DIND were registered, 9 were followed by secondary infarction (p < 0.05). In the magnesium group, 114 TCD-measurements showed an elevated MFV(> 140 cm/s). 7 were followed by new infarction. In control patients, 135 measurements showed elevated MFV, 32 were followed by new infarction (p < 0.05). 10 of 117 abnormal PCT-findings were followed by new infarction, compared to 30 of 122 in the control-group (p < 0.05). Conclusion: DIND, elevated MFV in TCD and abnormal PCT are findings which are associated with an increased risk to develop delayed secondary infarction. The results of this analysis suggest that magnesium-treatment may reduce the risk to develop infarction in a state of critical brain perfusion.},
  language  = {en}
}
@phdthesis{Schaefer2014,
  author    = {Sch{\"a}fer, Kristina},
  title     = {L{\"a}sst sich eine Vaskulitische Polyneuropathie mittels B-Bild-Sonographie der Beinnerven identifizieren?},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-104712},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2014},
  abstract  = {{\"U}ber die Nervensonographie wurde bereits in den 1980er Jahren erstmals berichtet. Die rasche Weiterentwicklung der Technik hat dazu gef{\"u}hrt, dass es inzwischen zahlreiche Fallberichte und einige Studien gibt, die sich mit der Darstellung peripherer Nerven durch Ultraschall als Mittel zur Diagnose verschiedener Nervpathologien besch{\"a}ftigen. Besonders bei der Diagnostik des epidemiologisch h{\"a}ufigen Karpaltunnelsyndroms ist die sonographische Beurteilung des N. medianus in dieser Lokalisation vielerorts bereits etablierter Bestandteil der Diagnostik. In der hier vorgelegten Studie sollte der Stellenwert der B-Bild-Sonographie peripherer Nerven am Unterschenkel f{\"u}r die Diagnose einer Vaskulitischen Neuropathie gepr{\"u}ft werden. Dazu musste zun{\"a}chst die Ultraschalluntersuchung spezieller Nerven am Unterschenkel etabliert werden. Diese ist technisch deutlich anspruchsvoller als die Darstellung von Karpaltunnelsyndrom oder Armplexus. Durch die f{\"u}nfmalige Untersuchung zehn junger Personen wurden ultraschalltechnisch leicht reproduzierbar anatomisch auffindbare und Anisotropie-vermeidende Abschnitte von N. suralis, N. peroneus communis, profundus, superfcialis und N. tibialis definiert und als Messpunkte der Studie zu Grunde gelegt. In die von der Ethikkommission der Medizinischen Fakult{\"a}t positiv beschiedene Studie wurden 26 Patienten/-innen, die klinisch und elektrophysiologisch nachgewiesen eine Polyneuropathie hatten und bei denen zur Ursachendiagnostik eine Biopsie und histologische Aufarbeitung des N. suralis durchgef{\"u}hrt wurde (Abteilung f{\"u}r Neuropathologie des Pathologischen Instituts der Universit{\"a}t sowie Histologielabor der Neurologischen Universit{\"a}tsklinik), sowie 26 Kontrollpersonen ohne klinischen Hinweis auf eine Polyneuropathie nach informiertem Einverst{\"a}ndnis aufgenommen. F{\"u}r jede/-n Patienten/-in wurde ein/-e Proband/-in gleichen Geschlechts mit einem Altersunterschied von h{\"o}chstens f{\"u}nf Jahren in die Kontrollgruppe aufgenommen. Alle 52 Untersuchten mussten erwachsen und 160 - 180 cm groß sein. Bei allen Patienten/-innen und Kontrollpersonen wurden jeweils der GD, der KD, der LD und die QSF des N. suralis am unteren Drittel der Wade und distal im Bereich des Außenkn{\"o}chels, des N. tibialis nahe des Innenkn{\"o}chels, des N. peroneus communis im Bereich des Fibulak{\"o}pfchens, des N. peroneus profundus am Fußr{\"u}cken und nahe der Großzehen und des N. peroneus superficialis im Bereich des distalen Schienbeins bestimmt. Alle gesuchten Nerven waren bei allen Versuchspersonen eindeutig identifizierbar. Die Untersuchungen wurden durch eine Untersucherin mit demselben Ger{\"a}t, geblindet f{\"u}r das Ergebnis der Histologie, durchgef{\"u}hrt. Das gew{\"a}hrleistete eine Konstanz in der schwierigen und mit Unsicherheiten behafteten Messung der Nervenstrukturen, was ausf{\"u}hrlich diskutiert wird. Ein statistisch signifikanter Unterschied zwischen den sonographisch erhobenen Messdaten der PNP-Gruppe und der Kontrollgruppe konnte bei 20 der 28 Parameter gezeigt werden. Bei 11 der 28 Parameter konnte zwischen Vaskulitis-Patienten/-innen und allen anderen, also PNP-Patienten/-innen und der Kontrollgruppe, ein statistisch signifikanter Unterschied festgestellt werden. Außerdem ergab die statistische Analyse bei drei der 28 Messgr{\"o}ßen einen statistisch signifikanten Unterschied zwischen Patienten/-innen mit und ohne Demyelinisierung des N. suralis in der feingeweblichen Untersuchung. Die sonographischen Ergebnisse der Vakulitis-Patienten/-innen unterschieden sich nicht von denen der PNP-Patienten/-innen mit anderer {\"A}tiologie. Es wurde auch kein statistisch signifikanter Unterschied zwischen den Werten der PNP-Patienten/-innen mit und ohne histologisch gesicherte entz{\"u}ndliche Komponente beobachtet. Gem{\"a}ß der histologischen Untersuchung der Biopsate wurde bei sechs Patienten/-innen eine Vaskulitis diagnostiziert. Bei f{\"u}nf dieser Patienten/-innen fielen teilweise Kaliberspr{\"u}nge im Sinne einer Zunahme der QSF oder Abflachung im Verlauf des N. suralis, N. peroneus superficialis und N. peroneus communis auf. Aber auch bei Patienten/-innen mit einer anderen Form der Polyneuropathie und einigen Kontrollpersonen waren Besonderheiten im sonographischen Bild einzelner Nerven zu beobachten. Mit der vorgelegten Untersuchung konnte zwar nicht gezeigt werden, dass die Nervensonographie einen Beitrag zur differentialdiagnostischen Abgrenzung Vaskulitischer Polyneuropathien leisten kann, der den Goldstandard invasiver Nervenbiopse entbehrlich machen k{\"o}nnte. Das war bei der histologischen Unterschiedlichkeit der besch{\"a}digten Nervenanatomie bei Vaskulitis aber auch nicht ernsthaft zu erwarten. Die vorgelegte Arbeit zeigt aber auch, dass kranke periphere Nerven von gesunden Nerven im Ultraschall unterscheidbar sind, wenn man wie hier systematisch mit 28 Parametern an sieben Messpunkten untersucht. Dies allerdings dauert auch f{\"u}r einen Ge{\"u}bten 40 bis 60 Minuten, so dass die Polyneuropathiediagnostik oder gar Differentialdiagnostik mittels Ultraschall aktuell noch als Forschungsinstrument an großen Fallzahlen anzusehen ist. Dabei wird es k{\"u}nftig f{\"u}r die Gruppenbildung der sonographisch Untersuchten neben {\"a}tiologischer und histologischer Gruppenbildung darauf ankommen, das Krankheitsbild besser zu definieren, d.h. Ausmaß von Demyelinisierung, Remyelinisierung und axonalem Untergang in geeignete Skalen zu fassen. Auch die Magnetresonanztomographie stellt eine Option als diagnostischer Baustein bei Vaskulitischer Polyneuropathie dar. Dieses bildgebende Verfahren kann bereits zur Diagnostik von traumatischen Nervverletzungen, Kompressionensyndromen, Raumforderungen im Bereich der Nerven und Plexusneuritis eingesetzt werden.},
  subject      = {Ultraschalldiagnostik},
  language  = {de}
}
@phdthesis{Wirsching2019,
  author    = {Wirsching, Isabelle},
  title     = {LTD-artige zentralmotorische Plastizit{\"a}t im Schubereignis bei Patienten mit Multipler Sklerose},
  doi       = {10.25972/OPUS-18003},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-180036},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {Die Multiple Sklerose ist eine chronisch entz{\"u}ndliche Erkrankung des zentralen Nervensystems. Durch ein komplexes Zusammenspiel von Genetik, Autoimmunvorg{\"a}ngen und proinflammatorischen Prozessen kommt es zur Demyelinisierung sowie zu axonalen Sch{\"a}den und kortikalen L{\"a}sionen (Calabrese et al., 2010; Ciccarelli et al., 2014; International Multiple Sclerosis Genetics et al., 2011; Leray et al., 2015). In den Industriel{\"a}ndern ist diese Erkrankung eine der h{\"a}ufigsten Ursachen f{\"u}r langfristige Behinderung bereits im fr{\"u}hen Lebensalter (Flores-Alvarado, Gabriel- 46 Ortiz, Pacheco-Mois, \& Bitzer-Quintero, 2015). Die Diskrepanz allerdings zwischen klinischer Symptomatik und den Befunden der Bildgebung (Barkhof, 2002) gibt Anlass daf{\"u}r, Adaptionsm{\"o}glichkeiten detailliert zu erforschen. Vorg{\"a}nge der Neuroplastizit{\"a}t mit LTP und LTD als Basismechanismen erscheinen dabei zunehmend Beachtung zu finden (Dayan \& Cohen, 2011; Zeller et al., 2011). Welche Rolle diese Prozesse allerdings im akuten Schub, w{\"a}hrend der h{\"a}ufig stark ausgepr{\"a}gten Symptomatik, insbesondere aber auch w{\"a}hrend ihrer R{\"u}ckbildung spielen, bleibt bisher weitgehend ungekl{\"a}rt. Eine Untersuchung zu stimulationsinduzierter LTP-artiger Plastizit{\"a}t im Schub deutete auf einen m{\"o}glichen Zusammenhang zwischen Ausmaß der Symptomr{\"u}ckbildung und PAS25-induziertem LTP-Effekt hin (Mori et al., 2014). In der vorliegenden Arbeit wurde komplement{\"a}r hierzu die stimulationsinduzierte LTD-artige Plastizit{\"a}t bei 19 MS- bzw. CIS-Patienten w{\"a}hrend des steroidbehandelten akuten Schubes untersucht. Als Kontrollgruppe wurden alters- und geschlechtsgematchte gesunde Probanden untersucht. Die Messungen wurden mithilfe eines Protokolls der assoziativen Paarstimulation durchgef{\"u}hrt. Paarstimulation wird die Kombination aus der peripher elektrischen und transkraniell magnetischen Stimulation genannt. Das in unserer Studie verwendete Protokoll sieht ein Interstimulusintervall von 10ms vor (PAS10). Der Effekt der Paarstimulation wird durch Messungen der Exzitabilit{\"a}t des motorischen Kortex mittels motorisch evozierter Potenziale (MEP) jeweils vor und nach der Intervention gemessen. Bei den MS-Patienten wurden diese Daten zum Zeitpunkt des Schubes (t1) und 12 Wochen danach (t2) erhoben; die gesunden Kontrollen wurden nur einmal gemessen. Daneben wurde bei den Schubpatienten zur Quantifizierung der klinischen Symptomatik jeweils zum ersten und zum zweiten Zeitpunkt der MSFC erhoben. Die MS-Patienten zeigten im akuten MS-Schub im Gegensatz zu der Kontrollgruppe aus Gesunden keinen LTD-artigen, sondern einen inversen, sprich einen signifikant LTP-artigen Effekt; dieser war zum Zeitpunkt t2 nicht mehr zu erkennen. Der Unterschied zwischen den PAS10-Effekten der MS- und der Kontrollgruppe war ebenfalls signifikant. Der Vergleich der MSFC-Werte der MS-Gruppe zwischen t1 und t2 erbrachte eine signifikante klinische Besserung. Eine signifikante Korrelation zwischen 47 den neurophysiologischen und klinischen Daten bzw. ihren Ver{\"a}nderungen zwischen t1 und t2 zeigte sich nicht. Diese Ergebnisse untermauern und erweitern bereits bestehende Hinweise, dass w{\"a}hrend der akuten Inflammationsprozesse des MS-Schubes ver{\"a}nderte Voraussetzungen f{\"u}r die Induzierbarkeit von Plastizit{\"a}t gegeben sind. Nicht nur, wie bereits gezeigt, die LTP-artige, sondern offenbar auch die LTD-artige assoziative Plastizit{\"a}t zeigt sich stark von den humoralen Ver{\"a}nderungen im steroidbehandelten Schub beeinflusst. Weitere Studien in st{\"a}rker vorselektierten Patientengruppen sollten der Frage nachgehen, inwieweit LTD-artige Plastizit{\"a}t sich in verschiedenen Subgruppen mit unterschiedlichen Schubsymptomen unterscheidet. Des Weiteren ist der Frage weiter nachzugehen, ob LTD-artige Plastizit{\"a}t funktional zur Adaption im Rahmen des Schubereignisses notwendig ist und inwieweit deren Unterdr{\"u}ckung bzw. Ersatz durch Langzeitpotenzierung potenziell einer Adaption im Wege steht. Sollten potenzielle Folgestudien best{\"a}tigen, dass LTD- und LTP-artige Plastizit{\"a}t im Schub m{\"o}glicherweise h{\"a}ufig dysfunktional ausgepr{\"a}gt ist und einer optimalen Regeneration entgegensteht, w{\"a}ren daraus praktische Implikationen zu ziehen. Die Entwicklung neuer Trainingsprogramme oder elektrophysiologischer Konzepte k{\"o}nnte ein n{\"a}chstes Ziel dieses Forschungszweiges sein, um potenziell dysfunktionale Plastizit{\"a}t zu vermeiden und physiologische Prozesse bereits im Schub zu f{\"o}rdern.},
  subject      = {Neuronale Plastizit{\"a}t},
  language  = {de}
}
@article{PeterkaOdorferSchwabetal.2020,
  author    = {Peterka, Manuel and Odorfer, Thorsten and Schwab, Michael and Volkmann, Jens and Zeller, Daniel},
  title     = {LSVT-BIG therapy in Parkinson's disease: physiological evidence for proprioceptive recalibration},
  series = {BMC Neurology},
  volume    = {20},
  journal   = {BMC Neurology},
  doi       = {10.1186/s12883-020-01858-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230084},
  year      = {2020},
  abstract  = {Background There is growing evidence for proprioceptive dysfunction in patients with Parkinson's disease (PD). The Lee Silvermann Voice Treatment-BIG therapy (LSVT-BIG), a special training program aiming at an increase of movement amplitudes in persons with PD (PwPD), has shown to be effective on motor symptoms. LSVT-BIG is conceptionally based on improving bradykinesia, in particular the decrement of repetitive movements, by proprioceptive recalibration. Objective To assess proprioceptive impairment in PwPD as compared to matched controls and to probe potential recalibration effects of the LSVT-BIG therapy on proprioception. Methods Proprioceptive performance and fine motor skills were assessed in 30 PwPD and 15 matched controls. Measurements with significant impairment in PwPD were chosen as outcome parameters for a standardized 4 weeks amplitude-based training intervention (LSVT-BIG) in 11 PwPD. Proprioceptive performance served as primary outcome measure. Secondary outcome measures included the motor part of the MDS-UPDRS, the nine-hole-peg test, and a questionnaire on quality of life. Post-interventional assessments were conducted at weeks 4 and 8. Results Compared to the control group, PwPD showed significantly larger pointing errors. After 4 weeks of LSVT-BIG therapy and even more so after an additional 4 weeks of continued training, proprioceptive performance improved significantly. In addition, quality of life improved as indicated by a questionnaire. Conclusion LSVT-BIG training may achieve a recalibration of proprioceptive processing in PwPD. Our data indicates a probable physiological mechanism of a symptom-specific, amplitude-based behavioral intervention in PwPD.},
  language  = {en}
}
@article{EstradaKrebbersVossetal.2018,
  author    = {Estrada, Veronica and Krebbers, Julia and Voss, Christian and Brazda, Nicole and Blazyca, Heinrich and Illgen, Jennifer and Seide, Klaus and J{\"u}rgens, Christian and M{\"u}ller, J{\"o}rg and Martini, Rudolf and Trieu, Hoc Khiem and M{\"u}ller, Hans Werner},
  title     = {Low-pressure micro-mechanical re-adaptation device sustainably and effectively improves locomotor recovery from complete spinal cord injury},
  series = {Communications Biology},
  volume    = {1},
  journal   = {Communications Biology},
  doi       = {10.1038/s42003-018-0210-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227357},
  year      = {2018},
  abstract  = {Traumatic spinal cord injuries result in impairment or even complete loss of motor, sensory and autonomic functions. Recovery after complete spinal cord injury is very limited even in animal models receiving elaborate combinatorial treatments. Recently, we described an implantable microsystem (microconnector) for low-pressure re-adaption of severed spinal stumps in rat. Here we investigate the long-term structural and functional outcome following microconnector implantation after complete spinal cord transection. Re-adaptation of spinal stumps supports formation of a tissue bridge, glial and vascular cell invasion, motor axon regeneration and myelination, resulting in partial recovery of motor-evoked potentials and a thus far unmet improvement of locomotor behaviour. The recovery lasts for at least 5 months. Despite a late partial decline, motor recovery remains significantly superior to controls. Our findings demonstrate that microsystem technology can foster long-lasting functional improvement after complete spinal injury, providing a new and effective tool for combinatorial therapies.},
  language  = {en}
}
@article{BrieseSaalBauernschubertLueningschroeretal.2020,
  author    = {Briese, Michael and Saal-Bauernschubert, Lena and L{\"u}ningschr{\"o}r, Patrick and Moradi, Mehri and Dombert, Benjamin and Surrey, Verena and Appenzeller, Silke and Deng, Chunchu and Jablonka, Sibylle and Sendtner, Michael},
  title     = {Loss of Tdp-43 disrupts the axonal transcriptome of motoneurons accompanied by impaired axonal translation and mitochondria function},
  series = {Acta Neuropathologica Communications},
  volume    = {8},
  journal   = {Acta Neuropathologica Communications},
  doi       = {10.1186/s40478-020-00987-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230322},
  year      = {2020},
  abstract  = {Protein inclusions containing the RNA-binding protein TDP-43 are a pathological hallmark of amyotrophic lateral sclerosis and other neurodegenerative disorders. The loss of TDP-43 function that is associated with these inclusions affects post-transcriptional processing of RNAs in multiple ways including pre-mRNA splicing, nucleocytoplasmic transport, modulation of mRNA stability and translation. In contrast, less is known about the role of TDP-43 in axonal RNA metabolism in motoneurons. Here we show that depletion of Tdp-43 in primary motoneurons affects axon growth. This defect is accompanied by subcellular transcriptome alterations in the axonal and somatodendritic compartment. The axonal localization of transcripts encoding components of the cytoskeleton, the translational machinery and transcripts involved in mitochondrial energy metabolism were particularly affected by loss of Tdp-43. Accordingly, we observed reduced protein synthesis and disturbed mitochondrial functions in axons of Tdp-43-depleted motoneurons. Treatment with nicotinamide rescued the axon growth defect associated with loss of Tdp-43. These results show that Tdp-43 depletion in motoneurons affects several pathways integral to axon health indicating that loss of TDP-43 function could thus make a major contribution to axonal pathomechanisms in ALS.},
  language  = {en}
}
@article{HornKristLiebetal.2021,
  author    = {Horn, A. and Krist, L. and Lieb, W. and Montellano, F. A. and Kohls, M. and Haas, K. and Gelbrich, G. and Bolay-Gehrig, S. J. and Morbach, C. and Reese, J. P. and St{\"o}rk, S. and Fricke, J. and Zoller, T. and Schmidt, S. and Triller, P. and Kretzler, L. and R{\"o}nnefarth, M. and Von Kalle, C. and Willich, S. N. and Kurth, F. and Steinbeis, F. and Witzenrath, M. and Bahmer, T. and Hermes, A. and Krawczak, M. and Reinke, L. and Maetzler, C. and Franzenburg, J. and Enderle, J. and Flinspach, A. and Vehreschild, J. and Schons, M. and Illig, T. and Anton, G. and Ungeth{\"u}m, K. and Finkenberg, B. C. and Gehrig, M. T. and Savaskan, N. and Heuschmann, P. U. and Keil, T. and Schreiber, S.},
  title     = {Long-term health sequelae and quality of life at least 6 months after infection with SARS-CoV-2: design and rationale of the COVIDOM-study as part of the NAPKON population-based cohort platform (POP)},
  series = {Infection},
  volume    = {49},
  journal   = {Infection},
  number    = {6},
  issn      = {0300-8126},
  doi       = {10.1007/s15010-021-01707-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-308960},
  pages     = {1277-1287},
  year      = {2021},
  abstract  = {Purpose Over the course of COVID-19 pandemic, evidence has accumulated that SARS-CoV-2 infections may affect multiple organs and have serious clinical sequelae, but on-site clinical examinations with non-hospitalized samples are rare. We, therefore, aimed to systematically assess the long-term health status of samples of hospitalized and non-hospitalized SARS-CoV-2 infected individuals from three regions in Germany. Methods The present paper describes the COVIDOM-study within the population-based cohort platform (POP) which has been established under the auspices of the NAPKON infrastructure (German National Pandemic Cohort Network) of the national Network University Medicine (NUM). Comprehensive health assessments among SARS-CoV-2 infected individuals are conducted at least 6 months after the acute infection at the study sites Kiel, W{\"u}rzburg and Berlin. Potential participants were identified and contacted via the local public health authorities, irrespective of the severity of the initial infection. A harmonized examination protocol has been implemented, consisting of detailed assessments of medical history, physical examinations, and the collection of multiple biosamples (e.g., serum, plasma, saliva, urine) for future analyses. In addition, patient-reported perception of the impact of local pandemic-related measures and infection on quality-of-life are obtained. Results As of July 2021, in total 6813 individuals infected in 2020 have been invited into the COVIDOM-study. Of these, about 36\% wished to participate and 1295 have already been examined at least once. Conclusion NAPKON-POP COVIDOM-study complements other Long COVID studies assessing the long-term consequences of an infection with SARS-CoV-2 by providing detailed health data of population-based samples, including individuals with various degrees of disease severity. Trial registration Registered at the German registry for clinical studies (DRKS00023742).},
  language  = {en}
}
@phdthesis{Fischer2004,
  author    = {Fischer, Matthias},
  title     = {Lokalisierung eines Ged{\"a}chtnisses bei Drosophila melanogaster},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-8050},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2004},
  abstract  = {Es konnte in dieser Arbeit gezeigt werden, daß das olfaktorische Kurzzeitged{\"a}chtnis von Drosophila melanogaster in den Pilzk{\"o}rpern lokalisiert ist. Zu Beginn dieser Doktorarbeit war bekannt, daß die Pilzk{\"o}rper notwendig f{\"u}r das Geruchsged{\"a}chtnis sind. Drei unabh{\"a}ngige Methoden der Ablation bzw. Ver{\"a}nderung der biochemischen Eigenschaften der Pilzk{\"o}rper hatten zu dem selben Ergebnis gef{\"u}hrt, daß funktionierende Pilzk{\"o}rper unentbehrlich f{\"u}r den Aufbau eines Geruchsged{\"a}chtnisses sind. Noch informativer als ein Experiment, in dem durch Zerst{\"o}rung einer Struktur eine Leistung unm{\"o}glich gemacht wird ist der umgekehrte Weg, der durch einen gewebespezifischen „rescue" die Leistung wiederherstellt. Dazu wurde in dieser Arbeit das wildtypische Allel des Gens rutabaga in rut-mutanten Fliegen mit Hilfe des Gal4/UAS-Systems ausschließlich in den Pilzk{\"o}rpern, bzw., im Gegenexperiment, nur außerhalb der Pilzk{\"o}rper zur Expression gebracht. rut kodiert f{\"u}r die Adenylatcyclase I, die mit synaptischer Plastizit{\"a}t bei Drosophila, Aplysia und M{\"a}usen in Verbindung gebracht wird. Man geht davon aus, daß synaptische Plastizit{\"a}t die molekulare Grundlage f{\"u}r Lernen und Ged{\"a}chtnis ist. Die AC I stellt cAMP her, dessen Menge und pr{\"a}zise Regulation die {\"U}bertragungsst{\"a}rke an Neuronen beeinflußt. Eine St{\"o}rung dieses Signalweges z. B. durch die rut-Mutation f{\"u}hrt zu einer Beeintr{\"a}chtigung des Ged{\"a}chtnisses bei Drosophila. rut wurde mit Hilfe des in Drosophila etablierten Gal4/UAS-Systems exprimiert: Der gewebespezifisch aktive Hefe-Transkriptionsfaktor Gal4 f{\"u}hrt dazu, daß das hinter einen Gal4-spezifischen UAS-Promotor klonierte wildtypische rut-Gen in denjenigen Zellen transkribiert wird, in denen der Transkriptionsfaktor vorhanden ist. Dies wurde in einer rut-Mutante durchgef{\"u}hrt, so daß in allen anderen Zellen keine funktionierende AC I vorhanden war. Die rut-abh{\"a}ngige synaptische Plastizit{\"a}t wurde damit ausschließlich auf die gew{\"u}nschten Regionen beschr{\"a}nkt. Das Expressionsmuster der Gal4-Linien wurde durch Immuncytochemie (Anti-Tau) sichtbar gemacht. Diese Fliegen wurden in einem klassischen Konditionierungsexperiment auf ihr Geruchs-Ged{\"a}chtnis untersucht. Dazu wurden einer Gruppe von Fliegen nacheinander 2 Ger{\"u}che pr{\"a}sentiert, von denen einer mit Elektroschocks gepaart war. Nach ca. 2 min konnten diese Fliegen sich f{\"u}r einen der beiden Ger{\"u}che entscheiden, die nun gleichzeitig aus 2 unterschiedlichen Richtungen dargeboten wurden. Je nach Lernleistung entschieden sich mehr oder weniger Fliegen f{\"u}r den vorher unbestraften Geruch. Es ergab sich, daß der Ort im Gehirn, an dem die wildtypische AC I exprimiert wurde, {\"u}ber die H{\"o}he des Ged{\"a}chtniswertes entschied: Die AC I ausschließlich in den Pilzk{\"o}rpern gew{\"a}hrte ein v{\"o}llig normales Ged{\"a}chtnis, wogegen die AC I außerhalb der Pilzk{\"o}rper das Ged{\"a}chtnis nicht gegen{\"u}ber der rut-Mutante verbessern konnte. Die Analyse der Expressionsverteilung von insgesamt 9 getesteten Fliegenlinien mißt {\"u}berdies dem \&\#61543;-Lobus des Pilzk{\"o}rpers eine besondere Bedeutung bei und l{\"a}ßt den Schluß zu, daß das hier untersuchte Ged{\"a}chtnis ausschließlich in den \&\#61543;-Loben lokalisiert ist. Dieses erfolgreiche rut-„rescue" - Experiment zeigt, daß rut-abh{\"a}ngige synaptische Plastizit{\"a}t ausschließlich in den Pilzk{\"o}rpern ausreichend f{\"u}r ein wildtypisches Ged{\"a}chtnis ist. Dieses Ergebnis vervollst{\"a}ndigt die Erkenntnisse von den Pilzk{\"o}rper-Ablationsexperimenten insofern, als nun die Aussage zutrifft, daß die Pilzk{\"o}rper notwendig und hinreichend f{\"u}r das olfaktorische Kurzzeitged{\"a}chtnis sind.},
  language  = {de}
}
@article{KollikowskiSchuhmannNieswandtetal.2020,
  author    = {Kollikowski, Alexander M. and Schuhmann, Michael K. and Nieswandt, Bernhard and M{\"u}llges, Wolfgang and Stoll, Guido and Pham, Mirko},
  title     = {Local Leukocyte Invasion during Hyperacute Human Ischemic Stroke},
  series = {Annals of Neurology},
  volume    = {87},
  journal   = {Annals of Neurology},
  number    = {3},
  doi       = {10.1002/ana.25665},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-212168},
  pages     = {466-479},
  year      = {2020},
  abstract  = {Objective Bridging the gap between experimental stroke and patients by ischemic blood probing during the hyperacute stage of vascular occlusion is crucial to assess the role of inflammation in human stroke and for the development of adjunct treatments beyond recanalization. Methods We prospectively observed 151 consecutive ischemic stroke patients with embolic large vessel occlusion of the anterior circulation who underwent mechanical thrombectomy. In all these patients, we attempted microcatheter aspiration of 3 different arterial blood samples: (1) within the core of the occluded vascular compartment and controlled by (2) carotid and (3) femoral samples obtained under physiological flow conditions. Subsequent laboratory analyses comprised leukocyte counting and differentiation, platelet counting, and the quantification of 13 proinflammatory human chemokines/cytokines. Results Forty patients meeting all clinical, imaging, interventional, and laboratory inclusion criteria could be analyzed, showing that the total number of leukocytes significantly increased under the occlusion condition. This increase was predominantly driven by neutrophils. Significant increases were also apparent for lymphocytes and monocytes, accompanied by locally elevated plasma levels of the T-cell chemoattractant CXCL-11. Finally, we found evidence that short-term clinical outcome (National Institute of Health Stroke Scale at 72 hours) was negatively associated with neutrophil accumulation. Interpretation We provide the first direct human evidence that neutrophils, lymphocytes, and monocytes, accompanied by specific chemokine upregulation, accumulate in the ischemic vasculature during hyperacute stroke and may affect outcome. These findings strongly support experimental evidence that immune cells contribute to acute ischemic brain damage and indicate that ischemic inflammation initiates already during vascular occlusion. Ann Neurol 2020;87:466-479},
  language  = {en}
}
@article{GarciaFernandezReinholdUeceyleretal.2023,
  author    = {Garc{\´i}a-Fern{\´a}ndez, Patricia and Reinhold, Colette and {\"U}{\c{c}}eyler, Nurcan and Sommer, Claudia},
  title     = {Local inflammatory mediators involved in neuropathic pain},
  series = {International Journal of Molecular Sciences},
  volume    = {24},
  journal   = {International Journal of Molecular Sciences},
  number    = {9},
  issn      = {1422-0067},
  doi       = {10.3390/ijms24097814},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313613},
  year      = {2023},
  abstract  = {Polyneuropathy (PNP) is a term to describe diseases of the peripheral nervous system, 50\% of which present with neuropathic pain. In some types of PNP, pain is restricted to the skin distally in the leg, suggesting a local regulatory process leading to pain. In this study, we proposed a pro-inflammatory pathway mediated by NF-κB that might be involved in the development of pain in patients with painful PNP. To test this hypothesis, we have collected nerve and skin samples from patients with different etiologies and levels of pain. We performed RT-qPCR to analyze the gene expression of the proposed inflammatory pathway components in sural nerve and in distal and proximal skin samples. In sural nerve, we showed a correlation of TLR4 and TNFα to neuropathic pain, and an upregulation of TNFα in patients with severe pain. Patients with an inflammatory PNP also presented a lower expression of TRPV1 and SIRT1. In distal skin, we found a reduced expression of TLR4 and miR-146-5p, in comparison to proximal skin. Our findings thus support our hypothesis of local inflammatory processes involved in pain in PNP, and further show disturbed anti-inflammatory pathways involving TRPV1 and SIRT1 in inflammatory PNP.},
  language  = {en}
}
@article{UeceylerValetKafkeetal.2014,
  author    = {{\"U}{\c{c}}eyler, Nurcan and Valet, Michael and Kafke, Waldemar and T{\"o}lle, Thomas R. and Sommer, Claudia},
  title     = {Local and Systemic Cytokine Expression in Patients with Postherpetic Neuralgia},
  doi       = {10.1371/journal.pone.0105269},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-113041},
  year      = {2014},
  abstract  = {Background Postherpetic neuralgia (PHN) is the painful complication of a varicella zoster virus reactivation. We investigated the systemic and local gene expression of pro- and anti-inflammatory cytokine expression in patients with PHN. Methods Thirteen patients with PHN at the torso (Th4-S1) were recruited. Skin punch biopsies were obtained from the painful and the contralateral painless body area for intraepidermal nerve fiber density (IENFD) and cytokine profiling. Additionally, blood was withdrawn for systemic cytokine expression and compared to blood values of healthy controls. We analyzed the gene expression of selected pro- and anti-inflammatory cytokines (tumor necrosis factor-alpha [TNF] and interleukins [IL]-1β, IL-2, and IL-8). Results IENFD was lower in affected skin compared to unaffected skin (p<0.05), while local gene expression of pro- and anti-inflammatory cytokines did not differ except for two patients who had 7fold higher IL-6 and 10fold higher IL-10 gene expression in the affected skin compared to the contralateral unaffected skin sample. Also, the systemic expression of cytokines in patients with PHN and in healthy controls was similar. Conclusion While the systemic and local expression of the investigated pro- and anti-inflammatory cytokines was not different from controls, this may have been influenced by study limitations like the low number of patients and different disease durations. Furthermore, other cytokines or pain mediators need to be considered.},
  language  = {en}
}
@article{PasosSteigerwaldReichetal.2019,
  author    = {Pasos, Uri E. Ramirez and Steigerwald, Frank and Reich, Martin M. and Matthies, Cordula and Volkmann, Jens and Reese, Ren{\´e}},
  title     = {Levodopa modulates functional connectivity in the upper beta band between bubthalamic nucleus and muscle activity in tonic and phasic motor activity patterns in Parkinson's disease},
  series = {Frontiers in Human Neuroscience},
  volume    = {13},
  journal   = {Frontiers in Human Neuroscience},
  number    = {223},
  doi       = {10.3389/fnhum.2019.00223},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201540},
  year      = {2019},
  abstract  = {Introduction: Striatal dopamine depletion disrupts basal ganglia function and causes Parkinson's disease (PD). The pathophysiology of the dopamine-dependent relationship between basal ganglia signaling and motor control, however, is not fully understood. We obtained simultaneous recordings of local field potentials (LFPs) from the subthalamic nucleus (STN) and electromyograms (EMGs) in patients with PD to investigate the impact of dopaminergic state and movement on long-range beta functional connectivity between basal ganglia and lower motor neurons. Methods: Eight PD patients were investigated 3 months after implantation of a deep brain stimulation (DBS)-system capable of recording LFPs via chronically-implanted leads (Medtronic, ACTIVA PC+S®). We analyzed STN spectral power and its coherence with EMG in the context of two different movement paradigms (tonic wrist extension vs. alternating wrist extension and flexion) and the effect of levodopa (L-Dopa) intake using an unbiased data-driven approach to determine regions of interest (ROI). Results: Two ROIs capturing prominent coherence within a grand average coherogram were identified. A trend of a dopamine effect was observed for the first ROI (50-150 ms after movement start) with higher STN-EMG coherence in medicated patients. Concerning the second ROI (300-500 ms after movement start), an interaction effect of L-Dopa medication and movement task was observed with higher coherence in the isometric contraction task compared to alternating movements in the medication ON state, a pattern which was reversed in L-Dopa OFF. Discussion: L-Dopa medication may normalize functional connectivity between remote structures of the motor system with increased upper beta coherence reflecting a physiological restriction of the amount of information conveyed between remote structures. This may be necessary to maintain simple movements like isometric contraction. Our study adds dynamic properties to the complex interplay between STN spectral beta power and the nucleus' functional connectivity to remote structures of the motor system as a function of movement and dopaminergic state. This may help to identify markers of neuronal activity relevant for more individualized programming of DBS therapy.},
  language  = {en}
}
@article{NeugebauerSchneiderKollmar2019,
  author    = {Neugebauer, Hermann and Schneider, Hauke and Kollmar, Rainer},
  title     = {Letter by Neugebauer et al. regarding article "Hypothermia after decompressive hemicraniectomy in treatment of malignant middle cerebral artery stroke: comment on the randomized clinical trial"},
  series = {Critical Care},
  volume    = {23},
  journal   = {Critical Care},
  doi       = {10.1186/s13054-019-2600-9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232268},
  year      = {2019},
  abstract  = {No abstract available.},
  language  = {en}
}
@phdthesis{Fackelmann2011,
  author    = {Fackelmann, Stefanie},
  title     = {Langzeitkorrelation evozierter Potentialparameter mit dem klinischen Verlauf bei Patienten mit Multipler Sklerose},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-64840},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Evozierte Potenziale werden bereits als Hilfsmittel zur Diagnosestellung der Multiplen Sklerose herangezogen. Das Spektrum der Verl{\"a}ufe der Erkrankung ist sehr unterschiedlich. Ziel der Studie war es, zu pr{\"u}fen, ob visuell (VEP), somatosensibel (SEP) und Magnet- (MEP) evozierte Potentiale durch das Aufdecken klinisch noch stummer L{\"a}sionen eine prognostische Bedeutung haben. Es wurden 94 Patienten bei Erstvorstellung sowie zum 5-Jahres- und 10-Jahresverlaufszeitpunkt untersucht. Es wurde ein Zusammenhang von MEP- und SEP-Scores mit dem sp{\"a}teren Behinderungsgrad, gemessen in Form der EDSS nach f{\"u}nf und zehn jahren gefunden, sofern die elektrophysiologischen Untersuchungen in den ersten beiden Jahren nach Erstmanifestation klinischer Symptome durchgef{\"u}hrt worden waren (Gruppe 1, 44 Patienten). F{\"u}r Gruppe 2 (50 Patienten), deren Erstuntersuchung sp{\"a}ter im Verlauf stattgefunden hatte (im Mittel 9,6a) konnte keine prognostische Bedeutung gesehen werden. Die Durchf{\"u}hrung multimodaler evozierter Potenziale ist kann somit eine Hilfestellung zur fr{\"u}hzeitigen Therapieentscheidung geben.},
  subject      = {Multiple Sklerose},
  language  = {de}
}
@phdthesis{Waldmann2021,
  author    = {Waldmann, Amelie Friederike},
  title     = {K{\"o}rperselbstgef{\"u}hl und Puppenhandillusion bei Patienten mit Morbus Parkinson im medikament{\"o}sen ON und OFF},
  doi       = {10.25972/OPUS-23200},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232009},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {In der vorliegenden Studie untersuchten wir das K{\"o}rperselbstgef{\"u}hl von Patienten mit Morbus Parkinson und altersgematchten gesunden Teilnehmern mithilfe der Puppenhandillusion. Bei diesem Paradigma wird dadurch, dass die verdeckte Hand der Testperson zeitgleich mit einer sichtbaren Puppenhand bestrichen wird, das Gef{\"u}hl hervorgerufen, die Kunsthand sei die eigene (gemessen mittels Fragebogen zur Illusion und propriozeptivem Drift). Eine zeitlich versetzte (asynchrone) Stimulation dient als Kontrollbedingung. Innerhalb der Parkinsonpatienten wurde dar{\"u}ber hinaus eine Untergruppe zus{\"a}tzlich im medikament{\"o}sen OFF-Zustand untersucht. Die Annahme, dass die Parkinsonerkrankung mit einer gest{\"o}rten K{\"o}rperselbstwahrnehmung einhergeht, spiegelt sich in den Ergebnissen wider: Bei den Patienten mit Parkinsonerkrankung trat unabh{\"a}ngig vom Stimulationsmodus ein h{\"o}herer propriozeptiver Drift als bei den Gesunden ein. Wurden die Patienten anschließend nach dem Erleben der Illusion befragt, fielen die Antworten allerdings nur w{\"a}hrend der asynchronen Durchf{\"u}hrung positiver als bei der Kontrollgruppe aus. Die Untersuchungen des Drifts und Fragebogens im ON- gegen{\"u}ber OFF-Zustand lieferten keinen Unterschied. Die vorliegende Studie liefert Hinweise darauf, dass die gemessenen Unterschiede bei Parkinsonpatienten gegen{\"u}ber Gesunden auf ein internes Rauschen eingehender sensorischer Signale beim Morbus Parkinson sowie auf die Beteiligung nicht-dopaminerger Systeme zur{\"u}ckzuf{\"u}hren sein k{\"o}nnten. Die zunehmende Aufmerksamkeit gegen{\"u}ber einer ver{\"a}nderten K{\"o}rperwahrnehmung bei Parkinsonpatienten und deren Grundlagen im Bereich der multisensorischen Integration k{\"o}nnte k{\"u}nftig neue M{\"o}glichkeiten in der ganzheitlichen Therapie liefern mit dem Ziel, die Lebensqualit{\"a}t der Patienten zu steigern.},
  subject      = {Parkinson-Krankheit},
  language  = {de}
}
@phdthesis{Weigl2020,
  author    = {Weigl, Anna},
  title     = {Korrelation zwischen subjektiver Fatigue und objektiven physischen und kognitiven Einschr{\"a}nkungen bei Multipler Sklerose: eine Querschnittsstudie},
  doi       = {10.25972/OPUS-21896},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218960},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Fatigue als ein „{\"u}berw{\"a}ltigendes Gef{\"u}hl von M{\"u}digkeit, Energielosigkeit und Ersch{\"o}pfung" stellt bei Patienten mit MS ein h{\"a}ufig auftretendes und oft im Alltag beeintr{\"a}chtigendes Symptom dar, das sowohl mit k{\"o}rperlichen als auch mit kognitiven Ersch{\"o}pfungssymptomen einhergeht. Die objektive Erfassung des Schweregrades der Fatigue beim einzelnen Patienten stellt ein Problem dar, da bisher keine objektiven Messverfahren zur Erfassung der Fatigue existieren. Im klinischen Alltag kommen meist Frageb{\"o}gen zum Einsatz, die das Ausmaß der subjektiven Beeintr{\"a}chtigung durch Fatigue im Alltag quantifizieren sollen. Ziel dieser Arbeit war es, zu untersuchen, inwieweit bestimmte im klinischen Alltag erhobene Parameter R{\"u}ckschl{\"u}sse auf die subjektive Fatigue bei Patienten mit MS erlauben, auch im Hinblick darauf, ob sich einzelne Parameter besonders zur Einsch{\"a}tzung der k{\"o}rperlichen bzw. kognitiven Fatigue eignen. Zudem sollte untersucht werden, ob die untersuchten klinischen Parameter bei bestimmten Patientengruppen besser als bei anderen R{\"u}ckschl{\"u}sse auf die subjektive Fatigue erlauben. Erfasst wurde die subjektive Fatigue durch das W{\"u}rzburger Ersch{\"o}pfungsinventar bei Multipler Sklerose (WEIMuS), einer Serie von Fragen, die zwischen k{\"o}rperlicher und kognitiver Fatigue unterscheiden. Dazu wurden Korrelationsanalysen zwischen der WEIMuS-Gesamtskala bzw. deren Subskalen f{\"u}r k{\"o}rperliche und kognitive Fatigue und EDSS-Wert, MSFC Z-Score einschließlich dessen Subscores und der Zeit des 50-Meter-Gehversuchs durchgef{\"u}hrt. Bez{\"u}glich der k{\"o}rperlichen Fatigue ergaben sich zwischen der WEIMuS-Subskala f{\"u}r k{\"o}rperliche Fatigue und dem EDSS sowie der Zeit des 50-Meter-Gehversuchs im Vergleich die st{\"a}rksten, absolut gesehen als mittelstark zu wertende, Korrelationen. Bez{\"u}glich der kognitiven Fatigue ergab sich die st{\"a}rkste Korrelation zwischen der WEIMuS-Subskala f{\"u}r kognitive Fatigue und dem PASAT3, die allerdings trotzdem als gering zu werten ist. Mit EDSS und 50-Meter-Gehversuch scheinen also zwei objektive klinische Parameter zu existieren, die in einem gewissen Maß auf die subjektive Fatigue r{\"u}ckschließen lassen. Ziel weiterer Untersuchungen wird es sein m{\"u}ssen, einen geeigneten klinischen Parameter zu finden, der bessere R{\"u}ckschl{\"u}sse auf die subjektive kognitive Fatigue erlaubt als der PASAT3. Zwischen der WEIMuS-Gesamtskala bzw. deren Subskalen f{\"u}r k{\"o}rperliche und kognitive Fatigue und Alter, Geschlecht und Erkrankungsdauer fanden sich bestenfalls geringe Korrelationen, weshalb diese Parameter ungeeignet erscheinen, Aussagen {\"u}ber die subjektive Fatigue zu machen. Durch die Einteilung der Patienten nach Alter und Geschlecht konnte untersucht werden, inwieweit diese Parameter Einfluss auf die untersuchten Zusammenh{\"a}nge zwischen klinischen Parametern und subjektiver Fatigue haben. Die Korrelationen zwischen den WEIMuS-Subskalen f{\"u}r k{\"o}rperliche und kognitive Fatigue mit den untersuchten klinischen Parametern waren f{\"u}r junge Patienten {\"u}berwiegend st{\"a}rker als f{\"u}r {\"a}ltere Patienten, insbesondere {\"a}ltere M{\"a}nner. Somit scheinen die untersuchten klinischen Parameter bei j{\"u}ngeren Patienten besser geeignet, Aussagen {\"u}ber die subjektive Fatigue zu machen als bei {\"a}lteren. Insgesamt ist festzuhalten, dass EDSS und 50-Meter-Gehversuch insbesondere bei jungen Patienten zu einer besseren objektiven Beurteilbarkeit vor allem der k{\"o}rperlichen Fatigue im klinischen Alltag beitragen k{\"o}nnen.},
  subject      = {Multiple Sklerose},
  language  = {de}
}
@phdthesis{Grohmann2023,
  author    = {Grohmann, Christoph},
  title     = {Kognitive Leistungsf{\"a}higkeit und Lebensqualit{\"a}t bei minimaler hepatischer Enzephalopathie - eine Pilotstudie zum Patient Reported Outcome in der Verlaufsdiagnostik},
  doi       = {10.25972/OPUS-30537},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305375},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2023},
  abstract  = {Die WHO definiert Gesundheit als v{\"o}lliges k{\"o}rperliches, geistiges und soziales Wohlbefinden. W{\"a}hrend diese ganzheitliche Betrachtungsweise seit Menschengedenken nahezu weltweit das Gesundheitswesen pr{\"a}gt, hat die Medizin in Europa mit der naturwissenschaftlichen Erkenntnisrevolution einen Sonderweg eingeschlagen. Hier wird der kranke Organismus in erster Linie als defekter Apparat gesehen, der mit ausgekl{\"u}gelter Technik zu reparieren ist. Aber auch pr{\"a}ziseste Qualit{\"a}tsarbeit st{\"o}ßt dabei oft an Leistungsgrenzen, weil sie als seelenlos erlebt wird. Daher sehen heute viele Fachgebiete die Notwendigkeit, ihre Behandlungskonzepte zu beseelen und ihre Behandlungserfolge auch anhand der subjektiv von Patienten empfundenen Lebensqualit{\"a}t zu beurteilen. F{\"u}r die Ermittlung dieses PRO kommen etablierte psychometrische Testverfahren in Frage, die sich auch f{\"u}r routinem{\"a}ßige Verlaufskontrollen eignen. In der vorliegenden Arbeit wurde am Beispiel der mHE gepr{\"u}ft, welchen Nutzen eine PRO-Bestimmung bei der Verlaufskontrolle haben kann. Dazu wurde eine prospektive Studie mit anf{\"a}nglich 75 Patienten durchgef{\"u}hrt. Alle hatten eine mHE und waren entweder alkoholbedingt oder aus anderen Gr{\"u}nden schwer leberkrank. An vier Terminen im Abstand von sechs Monaten wurden die kognitive Leistungsf{\"a}higkeit und der emotionale Status {\"u}berpr{\"u}ft. Die Patienten zeigten anf{\"a}nglich kognitive Einschr{\"a}nkungen, die sich im Verlauf der individuell abgestimmten Behandlung deutlich verbesserten oder ganz verschwanden. Die globale Testung mit dem MoCA ergab eine hochsignifikante Normalisierung im ersten Behandlungsjahr. Die MoCA-Werte am Studienanfang und -ende waren von der Erkrankungsursache unabh{\"a}ngig. Dieser Befund differenzierte sich in den Spezialtests TMT, PHES und NHPT. Hier zeigten die alkoholbedingt Erkrankten durchweg schlechtere Leistungen als die nicht-alkoholbedingt Erkrankten, erholten sich aber in der Regel auch deutlicher. Die seelische Gestimmtheit gem{\"a}ß BDI-II und die mit dem SF-36 MCS ermittelte psychosoziale Befindlichkeit waren in beiden Patientengruppen von Anfang an vergleichsweise g{\"u}nstig. Dabei hatten die alkoholbedingt Erkrankten die besseren Werte, speziell der BDI-II zeigte bei ihnen nach einem halben Jahr eine zus{\"a}tzliche und bleibende Stimmungsaufhellung an. Der SF-36 PCS zum K{\"o}rpererleben zeigte hingegen, dass sich die alkoholbedingt Erkrankten zu Studienbeginn in einer deutlich schlechteren Verfassung befanden. Diese verbesserte sich aber kontinuierlich, sodass nach 1,5 Jahren kein Unterschied mehr zu den nicht-alkoholbedingt Erkrankten bestand. Aus diesen Befunden und dem reichhaltigen Erfahrungsgut zur Alkoholkrankheit wird geschlossen, dass der Genesungsprozess bei alkoholbedingtem Leberversagen viel komplexer ist als bei nicht-alkoholbedingtem Leberversagen. Er k{\"o}nnte wesentlich mehr Zeit erfordern und wird offensichtlich anders erlebt. Dieser Patientengruppe k{\"o}nnten besondere physio- und gespr{\"a}chstherapeutische Angebote eine große Hilfe sein. Die Arbeit zeigt, dass es m{\"o}glich ist, mit wenig Aufwand komplement{\"a}r zu den klinischen Verlaufsbefunden einen informativen PRO-Bericht zu erhalten. Er hilft Angeh{\"o}rigen und medizinischem Personal, die pers{\"o}nlichen N{\"o}te und Hoffnungen der Patienten besser zu verstehen und gegebenenfalls einen Korrekturbedarf im Umgang zu erkennen. Hinzu kam im vorliegenden Fall die Erkenntnis, dass die alkoholbedingt Erkrankten in ihrem Kranksein anders betroffen waren. Die Gr{\"u}nde daf{\"u}r sind im Nachhinein plausibel, der Sachverhalt als solcher w{\"a}re aber ohne diese Spezialuntersuchung wohl nicht erkannt worden. Das Beispiel der PRO-Ermittlung bei der mHE macht den praktischen Wert einer Ber{\"u}cksichtigung des gesamtheitlichen Gesundheitskonzepts der WHO auch in der technikzentrierten „westlichen Medizin" deutlich.},
  subject      = {Encephalopathia hepatica},
  language  = {de}
}
@phdthesis{Steeg2023,
  author    = {Steeg, Felix Leonard},
  title     = {Kinematische und histomorphologische Charakterisierung des DYT1 Knock-in Mausmodells mit Trauma-induzierter Dystonie},
  doi       = {10.25972/OPUS-34580},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-345805},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2023},
  abstract  = {Die dem Formenkreis der Dystonien zugrundeliegenden, pathophysiologischen Grundlagen sind bislang nicht abschließend gekl{\"a}rt. F{\"u}r die DYT-TOR1A Dystonie ist bekannt, dass eine 3-bp Deletion eines GAG-Codons im TOR1A-Gen auf Chromosom 9 einen Funktionsverlust des Proteins TorsinA bewirkt. Dieser Funktionsverlust wird als ausl{\"o}sender Faktor f{\"u}r die Entstehung der DYT-TOR1A Dystonie angenommen. Nichtsdestotrotz entwickeln lediglich circa 30\% der Mutationstr{\"a}ger eine dystone Bewegungsst{\"o}rung. Als Grund daf{\"u}r wird eine Two-hit Hypothese diskutiert, die zus{\"a}tzlich zur genetischen Pr{\"a}disposition einen Umweltfaktor wie ein peripheres Trauma f{\"u}r die Entstehung von Symptomen postuliert. Durch eine standardisierte Quetschl{\"a}sion des N. ischiadicus konnte mit dieser Arbeit bei DYT1KI M{\"a}usen, die die ∆GAG-Mutation im endogenen Genom tragen, ein dystoner Ph{\"a}notyp hervorgerufen werden. Mit den Aufzeichnungen der M{\"a}use im TST wurde ein neuronales Netzwerk mittels der Software „DeepLabCut" trainiert, sodass die Dystonie-{\"a}hnlichen Bewegungen automatisiert erfasst und ausgewertet werden konnten. Das Netzwerk tr{\"a}gt dazu bei, dem vorwiegend klinischen Syndrom der Dystonie eine objektive kinematische Charakterisierung zu bieten und kann auf andere TSTs anderer Nagermodelle {\"u}bertragen werden. Ferner wurde {\"u}berpr{\"u}ft, ob die beobachteten Bewegungen durch Unterschiede in der Regeneration nach der Nervenquetschung zustande kamen. Elektroneurographien zeigten jedoch diesbez{\"u}glich keine Unterschiede zwischen wt und DYT1KI Tieren. Dar{\"u}ber hinaus sind mikromorphologische Prozesse im zentralen und peripheren Nervensystem Gegenstand dieser Studie. Einerseits konnten wir mittels Immunzellf{\"a}rbungen von T-, B-Zellen, Makrophagen und Mikroglia feststellen, dass sowohl zentral als auch peripher kein Anhalt darauf besteht, dass die beim DYT1KI Mausmodell entstandenen Dystonie-{\"a}hnlichen Bewegungen auf einer Dysfunktion oder Aktivierung des Immunsystems, wie es bei anderen neurologischen Erkrankungen bereits nachgewiesen wurde, eine Rolle spielt. Andererseits konnte anhand stereologischer Messungen gezeigt werden, dass bei den naiven DYT1KI Tieren im Vergleich zu wt Tieren dopaminerge Neurone der SN in der Anzahl verringert und im Volumen vergr{\"o}ßert sind, was auf einen Endoph{\"a}notypen hinweist. Bei den symptomatischen, nervengequetschten DYT1KI M{\"a}usen zeigte sich wiederum eine weitere, signifikante Zunahme der Hypertrophie der dopaminergen Neurone als Hinweis auf eine unmittelbar mit dem dystonen Ph{\"a}notypen in Zusammenhang stehende Ver{\"a}nderung. Zusammenfassend konnte ein symptomatisches Mausmodell von hoher translationaler Bedeutung etabliert werden, in dem sich Hinweise f{\"u}r eine dopaminerge Dysregulation ergaben und welches f{\"u}r weitere Studien, insbesondere therapeutischer Art, eingesetzt werden k{\"o}nnte.},
  subject      = {Dystonie},
  language  = {de}
}
@article{EhlingGoebBittneretal.2013,
  author    = {Ehling, Petra and G{\"o}b, Eva and Bittner, Stefan and Budde, Thomas and Ludwig, Andreas and Kleinschnitz, Christoph and Meuth, Sven G.},
  title     = {Ischemia-induced cell depolarization: does the hyperpolarization-activated cation channel HCN2 affect the outcome after stroke in mice?},
  series = {Experimental \& Translational Stroke Medicine},
  volume    = {5},
  journal   = {Experimental \& Translational Stroke Medicine},
  number    = {16},
  doi       = {10.1186/2040-7378-5-16},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131887},
  year      = {2013},
  abstract  = {Background Brain ischemia is known to include neuronal cell death and persisting neurological deficits. A lack of oxygen and glucose are considered to be key mediators of ischemic neurodegeneration while the exact mechanisms are yet unclear. In former studies the expression of two different two-pore domain potassium \((K_{2P})\) channels (TASK1, TREK1) were shown to ameliorate neuronal damage due to cerebral ischemia. In neurons, TASK channels carrying hyperpolarizing \(K^+\) leak currents, and the pacemaker channel HCN2, carrying depolarizing \(I_h\), stabilize the membrane potential by a mutual functional interaction. It is assumed that this ionic interplay between TASK and HCN2 channels enhances the resistance of neurons to insults accompanied by extracellular pH shifts. Methods In C57Bl/6 (wildtype, WT), \(hcn2^{+/+}\) and \(hcn2^{-/-}\) mice we used an in vivo model of cerebral ischemia (transient middle cerebral artery occlusion (tMCAO)) to depict a functional impact of HCN2 in stroke formation. Subsequent analyses comprise behavioural tests and hcn2 gene expression assays. Results After 60 min of tMCAO induction in WT mice, we collected tissue samples at 6, 12, and 24 h after reperfusion. In the infarcted neocortex, hcn2 expression analyses revealed a nominal peak of hcn2 expression 6 h after reperfusion with a tendency towards lower expression levels with longer reperfusion times. Hcn2 gene expression levels in infarcted basal ganglia did not change after 6 h and 12 h. Only at 24 h after reperfusion, hcn2 expression significantly decreases by ~55\%. However, 30 min of tMCAO in hcn2-/- as well as hcn2+/+ littermates induced similar infarct volumes. Behavioural tests for global neurological function (Bederson score) and motor function/coordination (grip test) were performed at day 1 after surgery. Again, we found no differences between the groups. Conclusions Here, we hypothesized that the absence of HCN2, an important functional counter player of TASK channels, affects neuronal survival during stroke-induced tissue damage. However, together with a former study on TASK3 these results implicate that both TASK3 and HCN2 which were supposed to be neuroprotective due to their pH-dependency, do not influence ischemic neurodegeneration during stroke in the tMCAO model.},
  language  = {en}
}
@article{EhlingGoebBittneretal.2013,
  author    = {Ehling, Petra and G{\"o}b, Eva and Bittner, Stefan and Budde, Thomas and Ludwig, Andreas and Kleinschnitz, Christoph and Meuth, Sven G.},
  title     = {Ischemia-induced cell depolarization: does the hyperpolarization-activated cation channel HCN2 affect the outcome after stroke in mice?},
  series = {Experimental \& Translational Stroke Medicine},
  volume    = {5},
  journal   = {Experimental \& Translational Stroke Medicine},
  number    = {16},
  doi       = {10.1186/2040-7378-5-16},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-129240},
  year      = {2013},
  abstract  = {Background Brain ischemia is known to include neuronal cell death and persisting neurological deficits. A lack of oxygen and glucose are considered to be key mediators of ischemic neurodegeneration while the exact mechanisms are yet unclear. In former studies the expression of two different two-pore domain potassium \((K_{2P})\) channels (TASK1, TREK1) were shown to ameliorate neuronal damage due to cerebral ischemia. In neurons, TASK channels carrying hyperpolarizing \(K^+\) leak currents, and the pacemaker channel HCN2, carrying depolarizing Ih, stabilize the membrane potential by a mutual functional interaction. It is assumed that this ionic interplay between TASK and HCN2 channels enhances the resistance of neurons to insults accompanied by extracellular pH shifts. Methods In C57Bl/6 (wildtype, WT), \(hcn2^{+/+}\) and \(hcn2^{-/-}\) mice we used an in vivo model of cerebral ischemia (transient middle cerebral artery occlusion (tMCAO)) to depict a functional impact of HCN2 in stroke formation. Subsequent analyses comprise behavioural tests and hcn2 gene expression assays. Results After 60 min of tMCAO induction in WT mice, we collected tissue samples at 6, 12, and 24 h after reperfusion. In the infarcted neocortex, hcn2 expression analyses revealed a nominal peak of hcn2 expression 6 h after reperfusion with a tendency towards lower expression levels with longer reperfusion times. Hcn2 gene expression levels in infarcted basal ganglia did not change after 6 h and 12 h. Only at 24 h after reperfusion, hcn2 expression significantly decreases by ~55\%. However, 30 min of tMCAO in hcn2-/- as well as hcn2+/+ littermates induced similar infarct volumes. Behavioural tests for global neurological function (Bederson score) and motor function/coordination (grip test) were performed at day 1 after surgery. Again, we found no differences between the groups. Conclusions Here, we hypothesized that the absence of HCN2, an important functional counter player of TASK channels, affects neuronal survival during stroke-induced tissue damage. However, together with a former study on TASK3 these results implicate that both TASK3 and HCN2 which were supposed to be neuroprotective due to their pH-dependency, do not influence ischemic neurodegeneration during stroke in the tMCAO model.},
  language  = {en}
}
@article{SchreweLillLiuetal.2015,
  author    = {Schrewe, L. and Lill, C. M. and Liu, T. and Salmen, A. and Gerdes, L. A. and Guillot-Noel, L. and Akkad, D. A. and Blaschke, P. and Graetz, C. and Hoffjan, S. and Kroner, A. and Demir, S. and B{\"o}hme, A. and Rieckmann, P. and El Ali, A. and Hagemann, N. and Hermann, D. M. and Cournu-Rebeix, I. and Zipp, F. and K{\"u}mpfel, T. and Buttmann, M. and Zettl, U. K. and Fontaine, B. and Bertram, L. and Gold, R. and Chan, A.},
  title     = {Investigation of sex-specific effects of apolipoprotein E on severity of EAE and MS},
  series = {Journal of Neuroinflammation},
  volume    = {12},
  journal   = {Journal of Neuroinflammation},
  number    = {234},
  doi       = {10.1186/s12974-015-0429-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-136252},
  year      = {2015},
  abstract  = {Background: Despite pleiotropic immunomodulatory effects of apolipoprotein E (apoE) in vitro, its effects on the clinical course of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS) are still controversial. As sex hormones modify immunomodulatory apoE functions, they may explain contentious findings. This study aimed to investigate sex-specific effects of apoE on disease course of EAE and MS. Methods: MOG\(_{35-55}\) induced EAE in female and male apoE-deficient mice was assessed clinically and histopathologically. apoE expression was investigated by qPCR. The association of the MS severity score (MSSS) and APOE rs429358 and rs7412 was assessed across 3237 MS patients using linear regression analyses. Results: EAE disease course was slightly attenuated in male apoE-deficient (apoE\(^{-/-}\)) mice compared to wildtype mice (cumulative median score: apoE\(^{-/-}\) = 2 [IQR 0.0-4.5]; wildtype = 4 [IQR 1.0-5.0]; n = 10 each group, p = 0.0002). In contrast, EAE was more severe in female apoE\(^{-/-}\) mice compared to wildtype mice (cumulative median score: apoE\(^{-/-}\) = 3 [IQR 2.0-4.5]; wildtype = 3 [IQR 0.0-4.0]; n = 10, p = 0.003). In wildtype animals, apoE expression during the chronic EAE phase was increased in both females and males (in comparison to naive animals; p < 0.001). However, in MS, we did not observe a significant association between MSSS and rs429358 or rs7412, neither in the overall analyses nor upon stratification for sex. Conclusions: apoE exerts moderate sex-specific effects on EAE severity. However, the results in the apoE knock-out model are not comparable to effects of polymorphic variants in the human APOE gene, thus pinpointing the challenge of translating findings from the EAE model to the human disease.},
  language  = {en}
}
@article{GruendahlWackerEinseleetal.2020,
  author    = {Gr{\"u}ndahl, Marie and Wacker, Beate and Einsele, Hermann and Heinz, Werner J.},
  title     = {Invasive fungal diseases in patients with new diagnosed acute lymphoblastic leukaemia},
  series = {Mycoses},
  volume    = {63},
  journal   = {Mycoses},
  number    = {10},
  doi       = {10.1111/myc.13151},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-217844},
  pages     = {1101 -- 1106},
  year      = {2020},
  abstract  = {Background Patients with acute leukaemia have a high incidence of fungal infections. This has primarily been shown in acute myeloid leukaemia and is different for acute lymphoblastic leukaemia. Until now no benefit of mould active prophylaxis has been demonstrated in the latter population. Methods In this retrospective single-centre study, we analysed the incidence, clinical relevance, and outcome of invasive fungal diseases (IFD) as well as the impact of antifungal prophylaxis for the first 100 days following the primary diagnosis of acute lymphoblastic leukaemia. Results In 58 patients a high rate of proven, probable, and possible fungal infections could be demonstrated with a 3.4\%, 8.6\%, and 17.2\% likelihood, respectively. The incidence might be even higher, as nearly 40\% of all patients had no prolonged neutropenia for more than 10 days, excluding those from the European Organization of Research and Treatment of cancer and the Mycoses Study Group criteria for probable invasive fungal disease. The diagnosed fungal diseases had an impact on the duration of hospitalisation, which was 13 days longer for patients with proven/probable IFD compared to patients with no signs of fungal infection. Use of antifungal prophylaxis did not significantly affect the risk of fungal infection. Conclusion Patients with acute lymphoblastic leukaemia are at high risk of acquiring an invasive fungal disease. Appropriate criteria to define fungal infections, especially in this population, and strategies to reduce the risk of infection, including antifungal prophylaxis, need to be further evaluated.},
  language  = {en}
}
@article{FluriHeinenKleinschnitz2013,
  author    = {Fluri, Felix and Heinen, Florian and Kleinschnitz, Christoph},
  title     = {Intravenous Thrombolysis in a Stroke Patient Receiving Rivaroxaban},
  series = {Cerebrovascular Disease Extra},
  volume    = {2013},
  journal   = {Cerebrovascular Disease Extra},
  number    = {3},
  doi       = {10.1159/000355839},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-128816},
  pages     = {153-155},
  year      = {2013},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{BrechtWeissbrichBraunetal.2012,
  author    = {Brecht, Isabel and Weissbrich, Benedikt and Braun, Julia and Toyka, Klaus Viktor and Weishaupt, Andreas and Buttmann, Mathias},
  title     = {Intrathecal, Polyspecific Antiviral Immune Response in Oligoclonal Band Negative Multiple Sclerosis},
  series = {PLoS One},
  volume    = {7},
  journal   = {PLoS One},
  number    = {7},
  doi       = {10.1371/journal.pone.0040431},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134426},
  pages     = {e40431},
  year      = {2012},
  abstract  = {Background: Oligoclonal bands (OCB) are detected in the cerebrospinal fluid (CSF) in more than 95\% of patients with multiple sclerosis (MS) in the Western hemisphere. Here we evaluated the intrathecal, polyspecific antiviral immune response as a potential diagnostic CSF marker for OCB-negative MS patients. Methodology/Principal Findings: We tested 46 OCB-negative German patients with paraclinically well defined, definite MS. Sixteen OCB-negative patients with a clear diagnosis of other autoimmune CNS disorders and 37 neurological patients without evidence for autoimmune CNS inflammation served as control groups. Antibodies against measles, rubella, varicella zoster and herpes simplex virus in paired serum and CSF samples were determined by ELISA, and virus-specific immunoglobulin G antibody indices were calculated. An intrathecal antibody synthesis against at least one neurotropic virus was detected in 8 of 26 (31\%) patients with relapsing-remitting MS, 8 of 12 (67\%) with secondary progressive MS and 5 of 8 (63\%) with primary progressive MS, in 3 of 16 (19\%) CNS autoimmune and 3 of 37 (8\%) non-autoimmune control patients. Antibody synthesis against two or more viruses was found in 11 of 46 (24\%) MS patients but in neither of the two control groups. On average, MS patients with a positive antiviral immune response were older and had a longer disease duration than those without. Conclusion: Determination of the intrathecal, polyspecific antiviral immune response may allow to establish a CSF-supported diagnosis of MS in OCB-negative patients when two or more of the four virus antibody indices are elevated.},
  language  = {en}
}
@article{WestermaierKoehlerLinsenmannetal.2015,
  author    = {Westermaier, Thomas and Koehler, Stefan and Linsenmann, Thomas and Kinderlen, Michael and Pakos, Paul and Ernestus, Ralf-Ingo},
  title     = {Intraoperative Myelography in Cervical Multilevel Stenosis Using 3D Rotational Fluoroscopy: Assessment of Feasibility and Image Quality},
  series = {Radiology Research and Practice},
  volume    = {2015},
  journal   = {Radiology Research and Practice},
  doi       = {10.1155/2015/498936},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125779},
  pages     = {498936},
  year      = {2015},
  abstract  = {Background. Intraoperative myelography has been reported for decompression control in multilevel lumbar disease. Cervical myelography is technically more challenging. Modern 3D fluoroscopy may provide a new opportunity supplying multiplanar images. This study was performed to determine the feasibility and image quality of intraoperative cervical myelography using a 3D fluoroscope. Methods. The series included 9 patients with multilevel cervical stenosis. After decompression, 10 mL of water-soluble contrast agent was administered via a lumbar drainage and the operating table was tilted. Thereafter, a 3D fluoroscopy scan (O-Arm) was performed and visually evaluated. Findings. The quality of multiplanar images was sufficient to supply information about the presence of residual stenosis. After instrumentation, metal artifacts lowered image quality. In 3 cases, decompression was continued because myelography depicted residual stenosis. In one case, anterior corpectomy was not completed because myelography showed sufficient decompression after 2-level discectomy. Interpretation. Intraoperative myelography using 3D rotational fluoroscopy is useful for the control of surgical decompression in multilevel spinal stenosis providing images comparable to postmyelographic CT. The long duration of contrast delivery into the cervical spine may be solved by preoperative contrast administration. The method is susceptible to metal artifacts and, therefore, should be applied before metal implants are placed.},
  language  = {en}
}
@article{HartmannsbergerDopplerStauberetal.2020,
  author    = {Hartmannsberger, Beate and Doppler, Kathrin and Stauber, Julia and Schlotter-Weigel, Beate and Young, Peter and Sereda, Michael W. and Sommer, Claudia},
  title     = {Intraepidermal nerve fiber density as biomarker in Charcot-Marie-Tooth disease 1A},
  series = {Brain Communications},
  volume    = {2},
  journal   = {Brain Communications},
  number    = {1},
  doi       = {10.1093/braincomms/fcaa012},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229538},
  year      = {2020},
  abstract  = {Charcot-Marie-Tooth disease type 1A, caused by a duplication of the gene peripheral myelin protein 22 kDa, is the most frequent subtype of hereditary peripheral neuropathy with an estimated prevalence of 1:5000. Patients suffer from sensory deficits, muscle weakness and foot deformities. There is no treatment approved for this disease. Outcome measures in clinical trials were based mainly on clinical features but did not evaluate the actual nerve damage. In our case-control study, we aimed to provide objective and reproducible outcome measures for future clinical trials. We collected skin samples from 48 patients with Charcot-Marie-Tooth type 1A, 7 patients with chronic inflammatory demyelinating polyneuropathy, 16 patients with small fibre neuropathy and 45 healthy controls. To analyse skin innervation, 40-µm cryosections of glabrous skin taken from the lateral index finger were double-labelled by immunofluorescence. The disease severity of patients with Charcot-Marie-Tooth type 1A was assessed by the Charcot-Marie-Tooth neuropathy version 2 score, which ranged from 3 (mild) to 27 (severe) and correlated with age (P < 0.01, R = 0.4). Intraepidermal nerve fibre density was reduced in patients with Charcot-Marie-Tooth type 1A compared with the healthy control group (P < 0.01) and negatively correlated with disease severity (P < 0.05, R = -0.293). Meissner corpuscle (MC) density correlated negatively with age in patients with Charcot-Marie-Tooth type 1A (P < 0.01, R = -0.45) but not in healthy controls (P = 0.07, R = 0.28). The density of Merkel cells was reduced in patients with Charcot-Marie-Tooth type 1A compared with healthy controls (P < 0.05). Furthermore, in patients with Charcot-Marie-Tooth type 1A, the fraction of denervated Merkel cells was highly increased and correlated with age (P < 0.05, R = 0.37). Analysis of nodes of Ranvier revealed shortened paranodes and a reduced fraction of long nodes in patients compared with healthy controls (both P < 0.001). Langerhans cell density was increased in chronic inflammatory demyelinating polyneuropathy, but not different in Charcot-Marie-Tooth type 1A compared with healthy controls. Our data suggest that intraepidermal nerve fibre density might be used as an outcome measure in Charcot-Marie-Tooth type 1A disease, as it correlates with disease severity. The densities of Meissner corpuscles and Merkel cells might be an additional tool for the evaluation of the disease progression. Analysis of follow-up biopsies will clarify the effects of Charcot-Marie-Tooth type 1A disease progression on cutaneous innervation.},
  language  = {en}
}
@article{BraeuningerKleinschnitzStoll2010,
  author    = {Braeuninger, Stefan and Kleinschnitz, C. and Stoll, G.},
  title     = {Interleukin-18 does not influence infarct volume or functional outcome in the early stage after transient focal brain ischemia in mice},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68141},
  year      = {2010},
  abstract  = {Interleukin-18 (IL-18) is a proinflammatory cytokine of the interleukin-1 family which is upregulated after cerebral ischemia. The functional role of IL-18 in cerebral ischemia is unknown. In the present study, we compared infarct size in IL-18 knock-out and wild-type mice 24 hours and 48 hours after 1-hour transient middle cerebral artery occlusion (tMCAO). Moreover, the functional outcome was evaluated in a modified Bederson score, foot fault test and grip test. There were no significant differences in infarct size or functional outcome tests between wild-type and IL-18 knock-out mice. These data indicate that the early inflammatory response to cerebral ischemia does not involve IL-18, in contrast to other interleukin-1 family members such as interleukin-1.},
  subject      = {Interleukin-18},
  language  = {en}
}
@article{KleinschnitzNiemczykRehbergWeberetal.2015,
  author    = {Kleinschnitz, Christoph and Niemczyk, Gabriele and Rehberg-Weber, Karin and Wernsd{\"o}rfer, Colin},
  title     = {Interferon Beta-1a (AVONEX®) as a treatment option for untreated patients with multiple sclerosis (AXIOM): a prospective, observational study},
  series = {International Journal of Molecular Sciences},
  volume    = {16},
  journal   = {International Journal of Molecular Sciences},
  doi       = {10.3390/ijms160715271},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148487},
  pages     = {15271-15286},
  year      = {2015},
  abstract  = {The efficacy and safety of first-line disease-modifying therapies (DMT) for relapsing-remitting multiple sclerosis (RRMS) has been demonstrated in pivotal, randomized trials, but these studies do not reflect the routine care setting where treatment gaps or switches are common. The Avonex as Treatment Option for Untreated MS Patients (AXIOM) trial assessed the efficacy of newly-initiated intramuscular interferon beta-1a (IM IFNb-1a) after a treatment-free interval, with particular consideration of the previous course of disease and therapy. The AXIOM trial was an open, 12-month, observational, non-interventional study with a retrospective and a prospective part conducted in Germany. RRMS patients with a treatment-free interval of at least three months were included and treated with IFNb-1a for up to 12 months. Relapse rate, disability progression, injection-related parameters and quality of life observed during the prospective part were compared with retrospectively-collected data. Two hundred and thirty five RRMS patients participated in AXIOM. The mean relapse rate decreased from 1.1 in the three months before baseline to 0.2 per quarter during the twelve-month observational period; the Multiple Sclerosis Functional Composite score improved during twelve months of IM IFNb-1a treatment, while the Expanded Disability Status Scale score did not change over the course of this study. Compared to previous DMTs (IM IFNb-1a, subcutaneous IFNb-1a (SC IFNb-1a), SC IFNb-1b, glatiramer acetate), the patients experienced less injection site reactions and flu-like symptoms, with a stated improved quality of life. IM IFNb-1a was effective and well accepted in RRMS patients with no or discontinued previous therapy. These results from the routine care setting may inform optimization of DMT treatment in RRMS, but need confirmation in further studies.},
  language  = {en}
}
@phdthesis{Soda2021,
  author    = {Soda, Hassan},
  title     = {Interdisziplin{\"a}res Schlaganfallmanagement anhand des Stroke Manager Programms - Studiendaten und Perspektiven f{\"u}r die Schlaganfallversorgung},
  doi       = {10.25972/OPUS-24206},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242061},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {Die Schlaganfallnachsorge in Deutschland wird von verschiedenen Leistungserbringern gepr{\"a}gt, die teilweise komplement{\"a}re und komplexe Dienstleistungen erbringen und sektoren{\"u}bergreifend arbeiten. In Bad Neustadt wurde in Kooperation mit der Universit{\"a}t W{\"u}rzburg und dem Zentrum f{\"u}r Telemedizin Bad Kissingen das Stroke Manager Programm entwickelt und evaluiert. Das strukturierte Nachsorgeprogramm Stroke Manager basiert auf einer standardisierten Informations- und Software Unterst{\"u}tzung von der Akutversorgung bis drei Monate nach Entlassung aus der station{\"a}ren Versorgung. Anhand der Ergebnisse des Stroke Manager Programms konnte eine vergleichsweise hohe Persistenz bzgl. der station{\"a}r verordneten medikament{\"o}sen Sekund{\"a}rpr{\"a}vention {\"u}ber einen Zeitraum von drei Monaten festgestellt werden, ebenso konnten wir nachweisen, dass sich das Programm positiv auf die Versorgungsqualit{\"a}t sowie die Patientenzufriedenheit nach Schlaganfall auswirken kann. Die im Stroke Manager-Programm betreuten Schlaganfallpatienten wiesen im Vergleich signifikante Unterschiede bei den Faktoren Rauchverhalten, Schlaganfallschweregrad und subjektive, globale Lebensqualit{\"a}t auf.},
  subject      = {Stroke Manager},
  language  = {de}
}
@article{GutknechtPoppWaideretal.2015,
  author    = {Gutknecht, Lise and Popp, Sandy and Waider, Jonas and Sommerlandt, Frank M. J. and G{\"o}ppner, Corinna and Post, Antonia and Reif, Andreas and van den Hove, Daniel and Strekalova, Tatyana and Schmitt, Angelika and Colaςo, Maria B. N. and Sommer, Claudia and Palme, Rupert and Lesch, Klaus-Peter},
  title     = {Interaction of brain 5-HT synthesis deficiency, chronic stress and sex differentially impact emotional behavior in Tph2 knockout mice},
  series = {Psychopharmacology},
  volume    = {232},
  journal   = {Psychopharmacology},
  doi       = {10.1007/s00213-015-3879-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-154586},
  pages     = {2429 -- 2441},
  year      = {2015},
  abstract  = {Rationale While brain serotonin (5-HT) function is implicated in gene-by-environment interaction (GxE) impacting the vulnerability-resilience continuum in neuropsychiatric disorders, it remains elusive how the interplay of altered 5-HT synthesis and environmental stressors is linked to failure in emotion regulation. Objective Here, we investigated the effect of constitutively impaired 5-HT synthesis on behavioral and neuroendocrine responses to unpredictable chronic mild stress (CMS) using a mouse model of brain 5-HT deficiency resulting from targeted inactivation of the tryptophan hydroxylase-2 (Tph2) gene. Results Locomotor activity and anxiety- and depression-like behavior as well as conditioned fear responses were differentially affected by Tph2 genotype, sex, and CMS. Tph2 null mutants (Tph2\(^{-/-}\)) displayed increased general metabolism, marginally reduced anxiety- and depression-like behavior but strikingly increased conditioned fear responses. Behavioral modifications were associated with sex-specific hypothalamic-pituitary-adrenocortical (HPA) system alterations as indicated by plasma corticosterone and fecal corticosterone metabolite concentrations. Tph2\(^{-/-}\) males displayed increased impulsivity and high aggressiveness. Tph2\(^{-/-}\) females displayed greater emotional reactivity to aversive conditions as reflected by changes in behaviors at baseline including increased freezing and decreased locomotion in novel environments. However, both Tph2\(^{-/-}\) male and female mice were resilient to CMS-induced hyperlocomotion, while CMS intensified conditioned fear responses in a GxE-dependent manner. Conclusions Our results indicate that 5-HT mediates behavioral responses to environmental adversity by facilitating the encoding of stress effects leading to increased vulnerability for negative emotionality.},
  language  = {en}
}
@phdthesis{Weis2018,
  author    = {Weis, Jessica},
  title     = {Innervation von Schweißdr{\"u}sen bei Patienten mit Morbus Parkinson},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161505},
  school      = {Universit{\"a}t W{\"u}rzburg},
  pages     = {97},
  year      = {2018},
  abstract  = {Die Forschung auf dem Gebiet der Parkinson-Erkrankung erlebt einen großen Wandel. Eindeutig ist mittlerweile, dass es zu kurz gefasst w{\"a}re diese Erkrankung auf die motorischen Symptome zu beschr{\"a}nken. In den letzten Jahren wurde durch intensive Forschung bewiesen, dass der idiopathische M. Parkinson eine multisystemische Erkrankung ist, welche verschiedene Teile des Nervensystems betreffen kann. Um die zugrundeliegende Pathophysiologie und die Beteiligung des autonomen Nervensystems bei M. Parkinson n{\"a}her zu untersuchen, wurden f{\"u}r diese Studie 30 Patienten mit idiopathischem M. Parkinson, 19 Patienten mit atypischem Parkinsonsyndrom und 30 gesunde Probanden am Universit{\"a}tsklinikum W{\"u}rzburg und an der Paracelsus-Elena-Klinik Kassel rekrutiert. Um Beeintr{\"a}chtigungen von groß-und kleinkalibrigen Nervenfasern einsch{\"a}tzen zu k{\"o}nnen, wurden eine Neurografie des N. suralis sowie eine quantitativ sensorische Testung durchgef{\"u}hrt. Zur Bewertung einer m{\"o}glichen toxischen Komponente von Levodopa gegen{\"u}ber einer direkten Sch{\"a}digung peripherer Nerven durch p-α-Synuclein wurden am Vitamin B12 Stoffwechsel beteiligte Proteine im Blut bestimmt. Alle Patienten und Probanden erhielten Hautbiopsien an Unterschenkel, Oberschenkel, R{\"u}cken und Finger, um anschließend eine immunhistochemische Aufarbeitung der Pr{\"a}parate durchf{\"u}hren zu k{\"o}nnen. Einerseits wurde die Beteiligung somatosensibler Nervenfasern mithilfe der Ausz{\"a}hlung intraepidermaler Nervenfasern (PGP 9.5) bewertet. Andererseits wurden die Schweißdr{\"u}sen auf Pathologien der sympathischen Nervenfasern (VIP, TH, SP, CGRP) und der sudomotorischen Synapsen (SNCA, Synaptophysin, SNAP 25) untersucht. Weiterhin wurde versucht p-α-Synuclein, als Biomarker der Parkinson-Erkrankung, in der Haut nachzuweisen. Positive Ergebnisse konnten hinsichtlich pathologischer Prozesse an den Synapsen erzielt werden. Es zeigte sich sowohl eine Reduktion von nativem α-Synuclein (Unterschenkel, p=0,009 und R{\"u}cken, p=0,013), Synaptophysin (Unterschenkel, p=0,007) als auch SNAP 25 (Unterschenkel, p=0,023) an den untersuchten Schweißdr{\"u}sen der Patientengruppe. Bei der Untersuchung von SNAP 25 zeigte sich des Weiteren eine negative Korrelation zwischen der SNAP 25 Dichte im Unterschenkel und p-α-Synuclein (p=0,007). Bei der Suche nach p-α-Synuclein wurden beinahe 72\% der Parkinson-Patienten positiv getestet, wohingegen keiner der gesunden Probanden p-α-Synuclein in der Haut zeigte. Weiterhin konnte bei 75\% der positiv getesteten Patienten mit Multisystematrophie p-α-Synuclein an somatosensiblen Nervenfasern des subepidermalen Plexus nachgewiesen werden, wohingegen es bei den M. Parkinson Patienten nur 13\% waren. Die Ergebnisse der zugrundeliegenden Arbeit zeigen, dass die Hautbiopsie als fr{\"u}hdiagnostisches Mittel und in der Differentialdiagnose ein hohes Potenzial hat. Die Erforschung von Pathologien an Synapsen wird in der Zukunft an großer Bedeutung gewinnen und scheint ein wichtiger Ansatz, um die Pathophysiologie des M. Parkinson genauer zu verstehen. Die Hautbiopsie k{\"o}nnte dabei von Vorteil sein, da sich Pathologien in vivo untersuchen lassen und man nicht auf Ergebnisse von Autopsien angewiesen ist.},
  subject      = {Parkinson-Krankheit},
  language  = {de}
}
@article{WieseDennstaedtHollmannetal.2021,
  author    = {Wiese, Teresa and Dennst{\"a}dt, Fabio and Hollmann, Claudia and Stonawski, Saskia and Wurst, Catherina and Fink, Julian and Gorte, Erika and Mandasari, Putri and Domschke, Katharina and Hommers, Leif and Vanhove, Bernard and Schumacher, Fabian and Kleuser, Burkard and Seibel, J{\"u}rgen and Rohr, Jan and Buttmann, Mathias and Menke, Andreas and Schneider-Schaulies, J{\"u}rgen and Beyersdorf, Niklas},
  title     = {Inhibition of acid sphingomyelinase increases regulatory T cells in humans},
  series = {Brain Communications},
  volume    = {3},
  journal   = {Brain Communications},
  number    = {2},
  doi       = {10.1093/braincomms/fcab020},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259868},
  year      = {2021},
  abstract  = {Genetic deficiency for acid sphingomyelinase or its pharmacological inhibition has been shown to increase Foxp3\(^+\) regulatory T-cell frequencies among CD4\(^+\) T cells in mice. We now investigated whether pharmacological targeting of the acid sphingomyelinase, which catalyzes the cleavage of sphingomyelin to ceramide and phosphorylcholine, also allows to manipulate relative CD4\(^+\) Foxp3\(^+\) regulatory T-cell frequencies in humans. Pharmacological acid sphingomyelinase inhibition with antidepressants like sertraline, but not those without an inhibitory effect on acid sphingomyelinase activity like citalopram, increased the frequency of Foxp3\(^+\) regulatory T cell among human CD4\(^+\) T cells in vitro. In an observational prospective clinical study with patients suffering from major depression, we observed that acid sphingomyelinase-inhibiting antidepressants induced a stronger relative increase in the frequency of CD4\(^+\) Foxp3\(^+\) regulatory T cells in peripheral blood than acid sphingomyelinase-non- or weakly inhibiting antidepressants. This was particularly true for CD45RA\(^-\) CD25\(^{high}\) effector CD4\(^+\) Foxp3\(^+\) regulatory T cells. Mechanistically, our data indicate that the positive effect of acid sphingomyelinase inhibition on CD4\(^+\) Foxp3\(^+\) regulatory T cells required CD28 co-stimulation, suggesting that enhanced CD28 co-stimulation was the driver of the observed increase in the frequency of Foxp3+ regulatory T cells among human CD4\(^+\) T cells. In summary, the widely induced pharmacological inhibition of acid sphingomyelinase activity in patients leads to an increase in Foxp3+ regulatory T-cell frequencies among CD4\(^+\) T cells in humans both in vivo and in vitro.},
  language  = {en}
}
@phdthesis{Feierabend2006,
  author    = {Feierabend, Stefanie},
  title     = {Informationsgehalt und Akzeptanz zweier K{\"o}rperschemata bei Patienten mit orofazialen Schmerzen},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-20970},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2006},
  abstract  = {Ziel dieser prospektiven multizentrischen Studie war der Vergleich 2 verschiedener Schemata zur Schmerzzeichnung bei Patienten mit orofazialen Schmerzen. 204 Patienten, die wegen orofazialer Schmerzen einen (Zahn)arzt aufsuchten, erhielten randomisiert 2 unterschiedliche K{\"o}rperschemata zur Schmerzzeichnung und einen Fragebogen zu deren Beurteilung. Ein Schema war dem Deutschen Schmerzfragebogen entnommen (Bogen A), das andere war mit der Intention entwickelt worden, den K{\"o}rper symmetrisch darzustellen und eine computergest{\"u}tzte Auswertung zu erm{\"o}glichen (Bogen B). Diese Zeichnung war großformatiger und enthielt ein vergr{\"o}ßertes Kopfschema. Die Antworten wurden bzgl. Pr{\"a}ferenz, Anzahl und Verteilung der Schmerzgebiete und {\"U}bereinstimmung zwischen den Schemata ausgewertet sowie mit Patientendaten korreliert. Die Daten von 183 Patienten waren auswertbar. Von 100/183 Patienten wurde Bogen B bevorzugt, von 57/183 Bogen A, unabh{\"a}ngig von Geschlecht, Alter und Erkrankungsdauer. Fast alle Patienten gaben mehr als ein Schmerzgebiet an, nur 43/183 Patienten Schmerzen ausschließlich in der Gesichts- und Kopfregion. Anzahl und Lokalisation der Schmerzgebiete waren zwischen den Schemata nicht unterschiedlich. Detaillierte Kopf- und K{\"o}rperschemata k{\"o}nnen ohne {\"U}berforderung der Patienten sinnvoll in die Diagnostik orofazialer Schmerzen eingesetzt werden und sind n{\"u}tzlich, um Komorbidit{\"a}ten zu erkennen.},
  language  = {de}
}
@article{SchischlevskijCordtsGuentheretal.2021,
  author    = {Schischlevskij, Pavel and Cordts, Isabell and G{\"u}nther, Ren{\´e} and Stolte, Benjamin and Zeller, Daniel and Schr{\"o}ter, Carsten and Weyen, Ute and Regensburger, Martin and Wolf, Joachim and Schneider, Ilka and Hermann, Andreas and Metelmann, Moritz and Kohl, Zacharias and Linker, Ralf A. and Koch, Jan Christoph and Stendel, Claudia and M{\"u}schen, Lars H. and Osmanovic, Alma and Binz, Camilla and Klopstock, Thomas and Dorst, Johannes and Ludolph, Albert C. and Boentert, Matthias and Hagenacker, Tim and Deschauer, Marcus and Lingor, Paul and Petri, Susanne and Schreiber-Katz, Olivia},
  title     = {Informal caregiving in amyotrophic lateral sclerosis (ALS): a high caregiver burden and drastic consequences on caregivers' lives},
  series = {Brain Sciences},
  volume    = {11},
  journal   = {Brain Sciences},
  number    = {6},
  issn      = {2076-3425},
  doi       = {10.3390/brainsci11060748},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-240981},
  year      = {2021},
  abstract  = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes progressive autonomy loss and need for care. This does not only affect patients themselves, but also the patients' informal caregivers (CGs) in their health, personal and professional lives. The big efforts of this multi-center study were not only to evaluate the caregivers' burden and to identify its predictors, but it also should provide a specific understanding of the needs of ALS patients' CGs and fill the gap of knowledge on their personal and work lives. Using standardized questionnaires, primary data from patients and their main informal CGs (n = 249) were collected. Patients' functional status and disease severity were evaluated using the Barthel Index, the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) and the King's Stages for ALS. The caregivers' burden was recorded by the Zarit Burden Interview (ZBI). Comorbid anxiety and depression of caregivers were assessed by the Hospital Anxiety and Depression Scale. Additionally, the EuroQol Five Dimension Five Level Scale evaluated their health-related quality of life. The caregivers' burden was high (mean ZBI = 26/88, 0 = no burden, ≥24 = highly burdened) and correlated with patients' functional status (r\(_p\) = -0.555, p < 0.001, n = 242). It was influenced by the CGs' own mental health issues due to caregiving (+11.36, 95\% CI [6.84; 15.87], p < 0.001), patients' wheelchair dependency (+9.30, 95\% CI [5.94; 12.66], p < 0.001) and was interrelated with the CGs' depression (r\(_p\) = 0.627, p < 0.001, n = 234), anxiety (r\(_p\) = 0.550, p < 0.001, n = 234), and poorer physical condition (r\(_p\) = -0.362, p < 0.001, n = 237). Moreover, female CGs showed symptoms of anxiety more often, which also correlated with the patients' impairment in daily routine (r\(_s\) = -0.280, p < 0.001, n = 169). As increasing disease severity, along with decreasing autonomy, was the main predictor of caregiver burden and showed to create relevant (negative) implications on CGs' lives, patient care and supportive therapies should address this issue. Moreover, in order to preserve the mental and physical health of the CGs, new concepts of care have to focus on both, on not only patients but also their CGs and gender-associated specific issues. As caregiving in ALS also significantly influences the socioeconomic status by restrictions in CGs' work lives and income, and the main reported needs being lack of psychological support and a high bureaucracy, the situation of CGs needs more attention. Apart from their own multi-disciplinary medical and psychological care, more support in care and patient management issues is required.},
  language  = {en}
}
@article{KreisslStoutWongetal.2011,
  author    = {Kreissl, Michael C. and Stout, David B. and Wong, Koon-Pong and Wu, Hsiao-Ming and Caglayan, Evren and Ladno, Waldemar and Zhang, Xiaoli and Prior, John and Reiners, Christoph and Huang, Sung-Cheng and Schelbert, Heinrich R.},
  title     = {Influence of Dietary Interventions and Insulin on Myocardial, Skeletal Muscle and Brain [18F]-Fluorodeoxyglucose Kinetics in Mice},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68775},
  year      = {2011},
  abstract  = {Background: We evaluated the effect of insulin stimulation and dietary changes on myocardial, skeletal muscle and brain [18F]-fluorodeoxyglucose (FDG) kinetics and uptake in vivo in intact mice. Methods: Mice were anesthetized with isoflurane and imaged under different conditions: non-fasted (n = 7; "controls"), non-fasted with insulin (2 IU/kg body weight) injected subcutaneously immediately prior to FDG (n = 6), fasted (n = 5), and fasted with insulin injection (n = 5). A 60-min small-animal PET with serial blood sampling and kinetic modeling was performed. Results: We found comparable FDG standardized uptake values (SUVs) in myocardium in the non-fasted controls and non-fasted-insulin injected group (SUV 45-60 min, 9.58 ± 1.62 vs. 9.98 ± 2.44; p = 0.74), a lower myocardial SUV was noted in the fasted group (3.48 ± 1.73; p < 0.001). In contrast, the FDG uptake rate constant (Ki) for myocardium increased significantly by 47\% in non-fasted mice by insulin (13.4 ± 3.9 ml/min/100 g vs. 19.8 ± 3.3 ml/min/100 g; p = 0.030); in fasted mice, a lower myocardial Ki as compared to controls was observed (3.3 ± 1.9 ml/min/100 g; p < 0.001). Skeletal muscle SUVs and Ki values were increased by insulin independent of dietary state, whereas in the brain, those parameters were not influenced by fasting or administration of insulin. Fasting led to a reduction in glucose metabolic rate in the myocardium (19.41 ± 5.39 vs. 3.26 ± 1.97 mg/min/100 g; p < 0.001), the skeletal muscle (1.06 ± 0.34 vs. 0.34 ± 0.08 mg/min/100 g; p = 0.001) but not the brain (3.21 ± 0.53 vs. 2.85 ± 0.25 mg/min/100 g; p = 0.19). Conclusions: Changes in organ SUVs, uptake rate constants and metabolic rates induced by fasting and insulin administration as observed in intact mice by small-animal PET imaging are consistent with those observed in isolated heart/muscle preparations and, more importantly, in vivo studies in larger animals and in humans. When assessing the effect of insulin on the myocardial glucose metabolism of non-fasted mice, it is not sufficient to just calculate the SUV - dynamic imaging with kinetic modeling is necessary.},
  subject      = {Insulin},
  language  = {en}
}
@article{BaumToykaBlueheretal.2021,
  author    = {Baum, Petra and Toyka, Klaus V. and Bl{\"u}her, Matthias and Kosacka, Joanna and Nowicki, Marcin},
  title     = {Inflammatory mechanisms in the pathophysiology of diabetic peripheral neuropathy (DN) — new aspects},
  series = {International Journal of Molecular Sciences},
  volume    = {22},
  journal   = {International Journal of Molecular Sciences},
  number    = {19},
  issn      = {1422-0067},
  doi       = {10.3390/ijms221910835},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284556},
  year      = {2021},
  abstract  = {The pathogenesis of diabetic neuropathy is complex, and various pathogenic pathways have been proposed. A better understanding of the pathophysiology is warranted for developing novel therapeutic strategies. Here, we summarize recent evidence from experiments using animal models of type 1 and type 2 diabetes showing that low-grade intraneural inflammation is a facet of diabetic neuropathy. Our experimental data suggest that these mild inflammatory processes are a likely common terminal pathway in diabetic neuropathy associated with the degeneration of intraepidermal nerve fibers. In contrast to earlier reports claiming toxic effects of high-iron content, we found the opposite, i.e., nutritional iron deficiency caused low-grade inflammation and fiber degeneration while in normal or high non-heme iron nutrition no or only extremely mild inflammatory signs were identified in nerve tissue. Obesity and dyslipidemia also appear to trigger mild inflammation of peripheral nerves, associated with neuropathy even in the absence of overt diabetes mellitus. Our finding may be the experimental analog of recent observations identifying systemic proinflammatory activity in human sensorimotor diabetic neuropathy. In a rat model of type 1 diabetes, a mild neuropathy with inflammatory components could be induced by insulin treatment causing an abrupt reduction in HbA1c. This is in line with observations in patients with severe diabetes developing a small fiber neuropathy upon treatment-induced rapid HbA1c reduction. If the inflammatory pathogenesis could be further substantiated by data from human tissues and intervention studies, anti-inflammatory compounds with different modes of action may become candidates for the treatment or prevention of diabetic neuropathy.},
  language  = {en}
}
@article{GrotemeyerFischerKoprichetal.2023,
  author    = {Grotemeyer, Alexander and Fischer, Judith F. and Koprich, James B. and Brotchie, Jonathan M. and Blum, Robert and Volkmann, Jens and Ip, Chi Wang},
  title     = {Inflammasome inhibition protects dopaminergic neurons from α-synuclein pathology in a model of progressive Parkinson's disease},
  series = {Journal of Neuroinflammation},
  volume    = {20},
  journal   = {Journal of Neuroinflammation},
  doi       = {10.1186/s12974-023-02759-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357652},
  year      = {2023},
  abstract  = {Neuroinflammation has been suggested as a pathogenetic mechanism contributing to Parkinson's disease (PD). However, anti-inflammatory treatment strategies have not yet been established as a therapeutic option for PD patients. We have used a human α-synuclein mouse model of progressive PD to examine the anti-inflammatory and neuroprotective effects of inflammasome inhibition on dopaminergic (DA) neurons in the substantia nigra (SN). As the NLRP3 (NOD-, LRR- and pyrin domain-containing 3)-inflammasome is a core interface for both adaptive and innate inflammation and is also highly druggable, we investigated the implications of its inhibition. Repeat administration of MCC950, an inhibitor of NLRP3, in a PD model with ongoing pathology reduced CD4\(^+\) and CD8\(^+\) T cell infiltration into the SN. Furthermore, the anti-inflammasome treatment mitigated microglial activation and modified the aggregation of α-synuclein protein in DA neurons. MCC950-treated mice showed significantly less neurodegeneration of DA neurons and a reduction in PD-related motor behavior. In summary, early inflammasome inhibition can reduce neuroinflammation and prevent DA cell death in an α-synuclein mouse model for progressive PD.},
  language  = {en}
}
@article{GoebVollZimmermannetal.2021,
  author    = {G{\"o}b, Vanessa and Voll, Maximilian G. and Zimmermann, Lena and Hemmen, Katharina and Stoll, Guido and Nieswandt, Bernhard and Schuhmann, Michael K. and Heinze, Katrin G. and Stegner, David},
  title     = {Infarct growth precedes cerebral thrombosis following experimental stroke in mice},
  series = {Scientific Reports},
  volume    = {11},
  journal   = {Scientific Reports},
  number    = {1},
  doi       = {10.1038/s41598-021-02360-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265791},
  year      = {2021},
  abstract  = {Ischemic stroke is among the leading causes of disability and death worldwide. In acute ischemic stroke, successful recanalization of occluded vessels is the primary therapeutic aim, but even if it is achieved, not all patients benefit. Although blockade of platelet aggregation did not prevent infarct progression, cerebral thrombosis as cause of secondary infarct growth has remained a matter of debate. As cerebral thrombi are frequently observed after experimental stroke, a thrombus-induced impairment of the brain microcirculation is considered to contribute to tissue damage. Here, we combine the model of transient middle cerebral artery occlusion (tMCAO) with light sheet fluorescence microscopy and immunohistochemistry of brain slices to investigate the kinetics of thrombus formation and infarct progression. Our data reveal that tissue damage already peaks after 8 h of reperfusion following 60 min MCAO, while cerebral thrombi are only observed at later time points. Thus, cerebral thrombosis is not causative for secondary infarct growth during ischemic stroke.},
  language  = {en}
}
@article{OdorferHomolaReichetal.2019,
  author    = {Odorfer, Thorsten M. and Homola, Gy{\"o}rgy A. and Reich, Martin M. and Volkmann, Jens and Zeller, Daniel},
  title     = {Increased finger-tapping related cerebellar activation in cervical dystonia, enhanced by transcranial stimulation: an indicator of compensation?},
  series = {Frontiers in Neurology},
  volume    = {10},
  journal   = {Frontiers in Neurology},
  number    = {231},
  issn      = {1664-2295},
  doi       = {10.3389/fneur.2019.00231},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196249},
  year      = {2019},
  abstract  = {Background: Cervical dystonia is a movement disorder causing abnormal postures and movements of the head. While the exact pathophysiology of cervical dystonia has not yet been fully elucidated, a growing body of evidence points to the cerebellum as an important node. Methods: Here, we examined the impact of cerebellar interference by transcranial magnetic stimulation on finger-tapping related brain activation and neurophysiological measures of cortical excitability and inhibition in cervical dystonia and controls. Bilateral continuous theta-burst stimulation was used to modulate cerebellar cortical excitability in 16 patients and matched healthy controls. In a functional magnetic resonance imaging arm, data were acquired during simple finger tapping before and after cerebellar stimulation. In a neurophysiological arm, assessment comprised motor-evoked potentials amplitude and cortical silent period duration. Theta-burst stimulation over the dorsal premotor cortex and sham stimulation (neurophysiological arm only) served as control conditions. Results: At baseline, finger tapping was associated with increased activation in the ipsilateral cerebellum in patients compared to controls. Following cerebellar theta-burst stimulation, this pattern was even more pronounced, along with an additional movement-related activation in the contralateral somatosensory region and angular gyrus. Baseline motor-evoked potential amplitudes were higher and cortical silent period duration shorter in patients compared to controls. After cerebellar theta-burst stimulation, cortical silent period duration increased significantly in dystonia patients. Conclusion: We conclude that in cervical dystonia, finger movements—though clinically non-dystonic—are associated with increased activation of the lateral cerebellum, possibly pointing to general motor disorganization, which remains subclinical in most body regions. Enhancement of this activation together with an increase of silent period duration by cerebellar continuous theta-burst stimulation may indicate predominant disinhibitory effects on Purkinje cells, eventually resulting in an inhibition of cerebello-thalamocortical circuits.},
  language  = {en}
}
@article{UeceylerKewenigKittelSchneideretal.2015,
  author    = {{\"U}{\c{c}}eyler, Nurcan and Kewenig, Susanne and Kittel-Schneider, Sarah and Fallgatter, Andreas J. and Sommer, Claudia},
  title     = {Increased cortical activation upon painful stimulation in fibromyalgia syndrome},
  series = {BMC Neurology},
  volume    = {15},
  journal   = {BMC Neurology},
  number    = {210},
  doi       = {10.1186/s12883-015-0472-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125230},
  year      = {2015},
  abstract  = {Background Fibromyalgia syndrome (FMS) is a chronic condition characterized by widespread pain and associated symptoms. We investigated cerebral activation in FMS patients by functional near-infrared spectroscopy (fNIRS). Methods Two stimulation paradigms were applied: a) painful pressure stimulation at the dorsal forearm; b) verbal fluency test (VFT). We prospectively recruited 25 FMS patients, ten patients with unipolar major depression (MD) without pain, and 35 healthy controls. All patients underwent neurological examination and all subjects were investigated with questionnaires (pain, depression, FMS, empathy). Results FMS patients had lower pressure pain thresholds than patients with MD and controls (p < 0.001) and reported higher pain intensity (p < 0.001). Upon unilateral pressure pain stimulation fNIRS recordings revealed increased bilateral cortical activation in FMS patients compared to controls (p < 0.05). FMS patients also displayed a stronger contralateral activity over the dorsolateral prefrontal cortex in direct comparison to patients with MD (p < 0.05). While all three groups performed equally well in the VFT, a frontal deficit in cortical activation was only found in patients with depression (p < 0.05). Performance and cortical activation correlated negatively in FMS patients (p < 0.05) and positively in patients with MD (p < 0.05). Conclusion Our data give further evidence for altered central nervous processing in patients with FMS and the distinction between FMS and MD.},
  language  = {en}
}
@article{UeceylerHomolaGonzalezetal.2014,
  author    = {{\"U}{\c{c}}eyler, Nurcan and Homola, Gy{\"o}rgy A. and Gonz{\´a}lez, Hans Guerrero and Kramer, Daniela and Wanner, Christoph and Weidemann, Frank and Solymosi, L{\´a}szl{\´o} and Sommer, Claudia},
  title     = {Increased Arterial Diameters in the Posterior Cerebral Circulation in Men with Fabry Disease},
  doi       = {10.1371/journal.pone.0087054},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-112614},
  year      = {2014},
  abstract  = {A high load of white matter lesions and enlarged basilar arteries have been shown in selected patients with Fabry disease, a disorder associated with an increased stroke risk. We studied a large cohort of patients with Fabry disease to differentially investigate white matter lesion load and cerebral artery diameters. We retrospectively analyzed cranial magnetic resonance imaging scans of 87 consecutive Fabry patients, 20 patients with ischemic stroke, and 36 controls. We determined the white matter lesion load applying the Fazekas score on fluid-attenuated inversion recovery sequences and measured the diameters of cerebral arteries on 3D-reconstructions of the time-of-flight-MR-angiography scans. Data of different Fabry patient subgroups (males - females; normal - impaired renal function) were compared with data of patients with stroke and controls. A history of stroke or transient ischemic attacks was present in 4/30 males (13\%) and 5/57 (9\%) females with Fabry disease, all in the anterior circulation. Only one man with Fabry disease showed confluent cerebral white matter lesions in the Fazekas score assessment (1\%). Male Fabry patients had a larger basilar artery (p<0.01) and posterior cerebral artery diameter (p<0.05) compared to male controls. This was independent of disease severity as measured by renal function and did not lead to changes in arterial blood flow properties. A basilar artery diameter of >3.2 mm distinguished between men with Fabry disease and controls (sensitivity: 87\%, specificity: 86\%, p<0.001), but not from stroke patients. Enlarged arterial diameters of the posterior circulation are present only in men with Fabry disease independent of disease severity.},
  language  = {en}
}
@article{WeiseBasseLuesebrinkKleinschnitzetal.2011,
  author    = {Weise, Gesa and Basse-L{\"u}sebrink, Thomas C. and Kleinschnitz, Christoph and Kampf, Thomas and Jakob, Peter M. and Stoll, Guido},
  title     = {In Vivo Imaging of Stepwise Vessel Occlusion in Cerebral Photothrombosis of Mice by \(^{19}\)F MRI},
  series = {PLoS One},
  volume    = {6},
  journal   = {PLoS One},
  number    = {12},
  doi       = {10.1371/journal.pone.0028143},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-137792},
  pages     = {e28143},
  year      = {2011},
  abstract  = {Background \(^{19}\)F magnetic resonance imaging (MRI) was recently introduced as a promising technique for in vivo cell tracking. In the present study we compared \(^{19}\)F MRI with iron-enhanced MRI in mice with photothrombosis (PT) at 7 Tesla. PT represents a model of focal cerebral ischemia exhibiting acute vessel occlusion and delayed neuroinflammation. Methods/Principal Findings Perfluorocarbons (PFC) or superparamagnetic iron oxide particles (SPIO) were injected intravenously at different time points after photothrombotic infarction. While administration of PFC directly after PT induction led to a strong \(^{19}\)F signal throughout the entire lesion, two hours delayed application resulted in a rim-like \(^{19}\)F signal at the outer edge of the lesion. These findings closely resembled the distribution of signal loss on T2-weighted MRI seen after SPIO injection reflecting intravascular accumulation of iron particles trapped in vessel thrombi as confirmed histologically. By sequential administration of two chemically shifted PFC compounds 0 and 2 hours after illumination the different spatial distribution of the \(^{19}\)F markers (infarct core/rim) could be visualized in the same animal. When PFC were applied at day 6 the fluorine marker was only detected after long acquisition times ex vivo. SPIO-enhanced MRI showed slight signal loss in vivo which was much more prominent ex vivo indicative for neuroinflammation at this late lesion stage. Conclusion Our study shows that vessel occlusion can be followed in vivo by \(^{19}\)F and SPIO-enhanced high-field MRI while in vivo imaging of neuroinflammation remains challenging. The timing of contrast agent application was the major determinant of the underlying processes depicted by both imaging techniques. Importantly, sequential application of different PFC compounds allowed depiction of ongoing vessel occlusion from the core to the margin of the ischemic lesions in a single MRI measurement.},
  language  = {en}
}