@article{SamperAgreloSchiraHeinenBeyeretal.2020, author = {Samper Agrelo, Iria and Schira-Heinen, Jessica and Beyer, Felix and Groh, Janos and B{\"u}termann, Christine and Estrada, Veronica and Poschmann, Gereon and Bribian, Ana and Jadasz, Janusz J. and Lopez-Mascaraque, Laura and Kremer, David and Martini, Rudolf and M{\"u}ller, Hans Werner and Hartung, Hans Peter and Adjaye, James and St{\"u}hler, Kai and K{\"u}ry, Patrick}, title = {Secretome analysis of mesenchymal stem cell factors fostering oligodendroglial differentiation of neural stem cells in vivo}, series = {International Journal of Molecular Sciences}, volume = {21}, journal = {International Journal of Molecular Sciences}, number = {12}, issn = {1422-0067}, doi = {10.3390/ijms21124350}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285465}, year = {2020}, abstract = {Mesenchymal stem cell (MSC)-secreted factors have been shown to significantly promote oligodendrogenesis from cultured primary adult neural stem cells (aNSCs) and oligodendroglial precursor cells (OPCs). Revealing underlying mechanisms of how aNSCs can be fostered to differentiate into a specific cell lineage could provide important insights for the establishment of novel neuroregenerative treatment approaches aiming at myelin repair. However, the nature of MSC-derived differentiation and maturation factors acting on the oligodendroglial lineage has not been identified thus far. In addition to missing information on active ingredients, the degree to which MSC-dependent lineage instruction is functional in vivo also remains to be established. We here demonstrate that MSC-derived factors can indeed stimulate oligodendrogenesis and myelin sheath generation of aNSCs transplanted into different rodent central nervous system (CNS) regions, and furthermore, we provide insights into the underlying mechanism on the basis of a comparative mass spectrometry secretome analysis. We identified a number of secreted proteins known to act on oligodendroglia lineage differentiation. Among them, the tissue inhibitor of metalloproteinase type 1 (TIMP-1) was revealed to be an active component of the MSC-conditioned medium, thus validating our chosen secretome approach.}, language = {en} } @article{RauschenbergerKnorrPisanietal.2021, author = {Rauschenberger, Lisa and Knorr, Susanne and Pisani, Antonio and Hallett, Mark and Volkmann, Jens and Ip, Chi Wang}, title = {Second hit hypothesis in dystonia: Dysfunctional cross talk between neuroplasticity and environment?}, series = {Neurobiology of Disease}, volume = {159}, journal = {Neurobiology of Disease}, doi = {10.1016/j.nbd.2021.105511}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265028}, year = {2021}, abstract = {One of the great mysteries in dystonia pathophysiology is the role of environmental factors in disease onset and development. Progress has been made in defining the genetic components of dystonic syndromes, still the mechanisms behind the discrepant relationship between dystonic genotype and phenotype remain largely unclear. Within this review, the preclinical and clinical evidence for environmental stressors as disease modifiers in dystonia pathogenesis are summarized and critically evaluated. The potential role of extragenetic factors is discussed in monogenic as well as adult-onset isolated dystonia. The available clinical evidence for a "second hit" is analyzed in light of the reduced penetrance of monogenic dystonic syndromes and put into context with evidence from animal and cellular models. The contradictory studies on adult-onset dystonia are discussed in detail and backed up by evidence from animal models. Taken together, there is clear evidence of a gene-environment interaction in dystonia, which should be considered in the continued quest to unravel dystonia pathophysiology.}, language = {en} } @phdthesis{Teuteberg2003, author = {Teuteberg, Philipp Wilhelm Friedemann}, title = {Schmerzhafte Mononeuropathie an C57BL/6 M{\"a}usen: Studien mit neutralisierenden Antik{\"o}rpern gegen Tumor-Nekrose-Faktor Alpha an zwei verschiedenen L{\"a}sionsmodellen}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-5346}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2003}, abstract = {Die vorliegende Arbeit befaßt sich mit zwei Modellen einer schmerzhaften Mononeuropathie an der C57BL/6-Maus sowie deren Beeinflussung durch neutralisierende AK gegen TNF. Daf{\"u}r wurden die Nn. ischiadici der M{\"a}use operativ manipuliert, zum einen in Form der CCI durch drei den Nerven einschn{\"u}rende Ligaturen und zum anderen in Form der PST durch Heraustrennen eines Drittels des Nervendurchmessers. Beide Operationsmodelle l{\"o}sten bei den M{\"a}usen eine schmerzhafte Neuropathie aus. Es wurde untersucht, inwieweit zum Zeitpunkt der jeweiligen Operation oder am 4. postoperativen Tag applizierte TNF-AK das Schmerz-assoziierte Verhalten beeinflussen konnten und ob diese Behandlung einen Einfluß auf die Zytokinexpression im Endoneurium, auf den Makrophageneinstrom und auf die Nervenregeneration hatte. Hierzu wurden Verhaltenstests sowie immunhistochemische und morphometrische Methoden verwendet. Aus den vorliegenden Ergebnissen kann geschlossen werden, daß der bei CCI vermutete Einfluß der epineuralen Entz{\"u}ndung auf das Schmerz-assoziierte Verhalten kleiner ist als urspr{\"u}nglich angenommen. Die Tatsache, daß zumindest auf einen Parameter (Hitzehyperalgesie) nicht nur die pr{\"a}ventive sondern auch die therapeutische TNF-Hemmung wirksam war, l{\"a}ßt auf einen Einsatz von TNF-Hemmern bei bestimmten Formen des neuropathischen Schmerzes zur Therapieerg{\"a}nzung hoffen. Obwohl die TNF-Hemmung in den hier verwendeten Dosen und Applikationsweisen keinen Einfluß auf die endoneurale Zytokinexpression, Makrophagendichte und Regeneration hatte, sollten zuk{\"u}nftige Studien diese Parameter unter variierten Applikationsbedingungen genauer untersuchen.}, language = {de} } @phdthesis{Papagianni2018, author = {Papagianni, Aikaterini}, title = {Schmerz-assoziierte elektrisch evozierte Potentiale (PREP) bei Patienten mit neuropathischen Schmerzsyndromen}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159728}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {In der vorliegenden Studie wurden 32 Patienten (19 Frauen, 13 M{\"a}nner, medianes Alter 50 Jahren, Spanne: 26-83 Jahre) mit einem klinisch akralen neuropathischen Schmerzsyndrom unterschiedlicher Genese mittels QST, PREP und Hautbiopsie untersucht. Unser Patientenkollektiv bestand aus drei Subgruppen: sechsen Patienten erf{\"u}llten die Kriterien einer SFN, acht Patienten hatten eine Neuropathie der großkalibrigen Nervenfasern mit zus{\"a}tzlicher Beeintr{\"a}chtigung der kleinkalibrigen Nervenfasern und weitere acht Patienten hatten ein akrales Schmerzsyndrom mit neuropathischen Charakteristika, ohne vorbekannte Diagnose einer Neuropathie der groß- oder kleinkalibrigen Nervenfasern. Die Patienten wurden mittels klinischer neurologischer Untersuchung, elektrophysiologischer Tests, QST, PREP und Hautbiopsie untersucht. Die Patientendaten wurden jeweils mit Daten großer Kontrollgruppen verglichen, die wir in unserer Klinik unter Angeh{\"o}rigen und Freunden unserer Patienten mit deren Einwilligung rekrutiert hatten. QST und die Hautbiopsie waren bei Patienten mit SFN und PNP jeweils auff{\"a}llig, bei akralem Schmerzsyndrom unklarer {\"A}tiologie hingegen unauff{\"a}llig. Nach elektrischer kutaner Stimulation aller drei K{\"o}rperregionen zeigte sich eine Amplitudenminderung der PREP-Reizantwort in allen Patientensubgruppen (7,5 µV in der SFN-Gruppe, 3,8 µV in der PNP-Gruppe, und 11,3 µV bei den Patienten mit akralem Schmerzsyndrom). Somit konnten wir zeigen, dass eine Kleinfaserpathologie in der Studienpopulation von Patienten mit neuropathischem Schmerzsyndrom besteht. Nur die Amplitudenminderung der PREP bildet diese Pathologie ab. Diese Daten erlauben uns die eingangs aufgestellte Hypothese, dass PREP zur Diagnostik bei Frage nach Kleinfaserbeteiligung geeignet ist, positiv zu belegen. PREP ist eine nicht-invasive Methode f{\"u}r die Evaluation der Funktion v.a. der Aδ-Faser mit standardisiertem Ablaufprotokoll zur Erhebung von reproduzierbaren Daten. Sie kann bei Patienten mit der Anamnese eines akralen neuropathischen Schmerzsyndroms einen objektiven Hinweis auf eine Dysfunktion der kleinkalibrigen Nervenfasern, auch wenn bereits etablierte Methoden (QST und Hautbiopsie) unauff{\"a}llig bleiben, erbringen. Entsprechend k{\"o}nnen die PREP eine wertvolle Erg{\"a}nzung der klinischen Untersuchungsbatterie f{\"u}r die Evaluation der Funktion der kleinkalibrigen Nervenfasern sein.}, subject = {PREP}, language = {de} } @phdthesis{Auchter2021, author = {Auchter, Antonia}, title = {Schlafassoziierte Ver{\"a}nderung der lokalen Feldpotential Aktivit{\"a}t im Nucleus subthalamicus bei Patienten mit Morbus Parkinson}, doi = {10.25972/OPUS-23782}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-237822}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {Die tiefe Hirnstimulation ist eine etablierte und hocheffiziente operative Behandlungsmethode f{\"u}r Patienten mit idiopathischem Parkinson- Syndrom (IPS). Als Zielgebiet dient in den meisten F{\"a}llen der Nucleus subthalamicus. Die Indikationen zur Implantation einer tiefen Hirnstimulation (THS) sind medikament{\"o}s nicht behandelbare motorische Fluktuationen und Dyskinesien oder ein medikament{\"o}s nicht kontrollierbarer Tremor. Bislang erfolgt eine kontinuierliche Stimulation. Little et al. konnten jedoch bereits in ihrer 2013 ver{\"o}ffentlichen Studie zeigen, dass eine adaptive Stimulation, gemessen am UPDRS, um 27 \% effektiver war und entsprechend die Stimulationszeit um 56 \% gesenkt werden konnte. Voraussetzung f{\"u}r die Anwendbarkeit einer adaptiven Stimulation im klinischen Alltag ist der Nachweis eines oder mehrerer Physiomarker, welche als R{\"u}ckkopplungssignal f{\"u}r den Stimulationsbeginn dienen. Diese Marker m{\"u}ssen verl{\"a}sslich mit dem Auftreten und der Auspr{\"a}gung der Bewegungsst{\"o}rungen korrelieren. Die Systeme m{\"u}ssen die Signale auslesen und entsprechend darauf reagieren k{\"o}nnen, damit ein sogenanntes Closed- loop- Verfahren entstehen kann. Bei diesen Markern handelt es sich um sogenannte lokale Feldpotenzialaktivit{\"a}ten, das heißt niederfrequente Potential{\"a}nderungen von Zellen in subkortikalen Arealen des Gehirns, welche {\"u}ber Elektroden der THS abgeleitet werden k{\"o}nnen. Der Stimulator Activa PC+S (Medtronic) erm{\"o}glicht es erstmalig Aufzeichnungen von LFP- Daten, außerhalb eines experimentellen Laboraufbaus, mittels dauerhaft implantiertem Ger{\"a}t vorzunehmen und damit auch Langzeitanalysen durchzuf{\"u}hren. Erkenntnisse vergangener Studien ergaben, dass die synchronisierte, pathologisch gesteigerte oszillatorische Aktivit{\"a}t im Beta-Frequenzband (13- 35 Hz) eine bedeutende Rolle im Bezug auf die Pathophysiologie des IPS spielt und als krankheitsspezifische Aktivit{\"a}t gilt. Es konnte bereits belegt werden, dass die Verbesserung der motorischen Symptome (Bradykinese und Rigor) mit dem Ausmaß der Suppression der Betaband- Aktivit{\"a}t korreliert. Die Betabandaktivit{\"a}t als lokale Feldpotentialaktivit{\"a}t kann als Physiomarker einer adaptiven Stimulation dienen. Unser Hauptaugenmerk galt daher der Analyse der Betabandaktivit{\"a}t oder anderer Frequenzbereiche w{\"a}hrend des Schlafes um hier die THS bedarfsgerecht einzusetzen. Hierf{\"u}r wurden n{\"a}chtliche subkortikale LFP- Aufzeichnungen parallel zur Schlaf- Polysomnographie durchgef{\"u}hrt. Zudem erfolgte in der vorliegenden Arbeit sowohl in unserem Vorversuch als auch in unserem Hauptversuch die Anwendung des UPDRS Teil III zur Erfassung der motorischen Symptome, sowie die Durchf{\"u}hrung von Frageb{\"o}gen zur Erfassung der nicht- motorischen Symptome, insbesondere des Schlafes vor und nach Implantation der tiefen Hirnstimulation. Wir konnten belegen, dass es nach Implantation der THS zu einer Erh{\"o}hung der Schlafeffizienz und zu einer Erh{\"o}hung des Anteils der Schlafstadien II und III und damit einhergehend zu einer Steigerung der Schlafqualit{\"a}t kommt. {\"U}bereinstimmend mit anderen Studien konnten wir zeigen, dass sich die Motorik unter Stimulation deutlich verbessert. Im Vorversuch reduzierte sich der mittlere pr{\"a}operative MDS- UPDRS III im MedsOFF verglichen mit dem mittleren postoperativ MDS- UPDRS III im MedsOFF/StimON um 37 \%. In der PC+S- Studie imponierte eine Reduktion um 67\%. Zudem zeigte sich eine Reduktion der nicht- motorischen Symptome durch die THS, insbesondere in der Kategorie Schlaf. Die Ergebnisse der vorliegenden Arbeit ergaben außerdem, dass die Betabandaktivität im Schlafstadium II und vor allem im Schlafstadium III am geringsten ist. Im Schlafstadium I und REM ist die Betabandaktivit{\"a}t höher als im Schlafstadium II und III. Hierbei war entscheidend, dass die Patienten eine klar abgrenzbare Betabandaktivit{\"a}t im Wachstadium aufwiesen und die Elektrodenkontakte im dorsolateralen Kerngebiet des STN lokalisiert waren. Gegenl{\"a}ufig dazu verh{\"a}lt sich die Deltaaktivität. Sie ist im Schlafstadium II und besonders im Stadium III am h{\"o}chsten. Stadium I ist mit durchschnittlich um 7,3 \% niedriger als im Wachstadium. Am geringsten ist sie jedoch im REM-Schlafstadium. Indem wir mit der Betabandaktivit{\"a}t und Deltaaktivit{\"a}t in den einzelnen Schlafstadien einen stabilen und reproduzierbaren Physiomarker finden konnten, sind wir unserem Ziel der adaptiven THS ein St{\"u}ck n{\"a}her gekommen.}, subject = {Parkinson}, language = {de} } @article{SteinhardtCejkaChenetal.2024, author = {Steinhardt, Maximilian J. and Cejka, Vladimir and Chen, Mengmeng and B{\"a}uerlein, Sabrina and Sch{\"a}fer, Julia and Adrah, Ali and Ihne-Schubert, Sandra M. and Papagianni, Aikaterini and Kort{\"u}m, K. Martin and Morbach, Caroline and St{\"o}rk, Stefan}, title = {Safety and tolerability of SGLT2 inhibitors in cardiac amyloidosis — a clinical feasibility study}, series = {Journal of Clinical Medicine}, volume = {13}, journal = {Journal of Clinical Medicine}, number = {1}, issn = {2077-0383}, doi = {10.3390/jcm13010283}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-356024}, year = {2024}, abstract = {Sodium-glucose transport protein 2 inhibitors (SGLT2i) slow the progression of renal dysfunction and improve the prognosis of patients with heart failure. Amyloidosis constitutes an important subgroup for which evidence is lacking. Amyloidotic fibrils originating from misfolded transthyretin and light chains are the causal agents in ATTR and AL amyloidosis. In these most frequent subtypes, cardiac involvement is the most common organ manifestation. Because cardiac and renal function frequently deteriorate over time, even under best available treatment, SGLT2i emerge as a promising treatment option due to their reno- and cardioprotective properties. We retrospectively analyzed patients with cardiac amyloidosis, who received either dapagliflozin or empagliflozin. Out of 79 patients, 5.1\% had urinary tract infections; 2 stopped SGLT2i therapy; and 2.5\% died unrelated to the intake of SGLT2i. No genital mycotic infections were observed. As expected, a slight drop in the glomerular filtration rate was noted, while the NYHA functional status, cardiac and hepatic function, as well as the 6 min walk distance remained stable over time. These data provide a rationale for the use of SGLT2i in patients with amyloidosis and concomitant cardiac or renal dysfunction. Prospective randomized data are desired to confirm safety and to prove efficacy in this increasingly important group of patients.}, language = {en} } @article{VogtKollikowskiWeidneretal.2022, author = {Vogt, Marius L. and Kollikowski, Alexander M. and Weidner, Franziska and Strinitz, Marc and Feick, J{\"o}rn and Essig, Fabian and Neugebauer, Herrmann and Haeusler, Karl Georg and Pham, Mirko and Maerz, Alexander}, title = {Safety and Effectiveness of the New Generation APERIO® Hybrid Stent-retriever Device in Large Vessel Occlusion Stroke}, series = {Clinical Neuroradiology}, volume = {32}, journal = {Clinical Neuroradiology}, number = {1}, doi = {10.1007/s00062-021-01122-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-264817}, pages = {141-151}, year = {2022}, abstract = {Background It is unknown whether technological advancement of stent-retriever devices influences typical observational indicators of safety or effectiveness. Methods Observational retrospective study of APERIO® (AP) vs. new generation APERIO® Hybrid (APH) (Acandis®, Pforzheim, Germany) stent-retriever device (01/2019-09/2020) for mechanical thrombectomy (MT) in large vessel occlusion (LVO) stroke. Primary effectiveness endpoint was successful recanalization eTICI (expanded Thrombolysis In Cerebral Ischemia) ≥ 2b67, primary safety endpoint was occurrence of hemorrhagic complications after MT. Secondary outcome measures were time from groin puncture to first pass and successful reperfusion, and the total number of passes needed to achieve the final recanalization result. Results A total of 298 patients with LVO stroke who were treated by MT matched the inclusion criteria: 148 patients (49.7\%) treated with AP vs. 150 patients (50.3\%) treated with new generation APH. Successful recanalization was not statistically different between both groups: 75.7\% for AP vs. 79.3\% for APH; p = 0.450. Postinterventional hemorrhagic complications and particularly subarachnoid hemorrhage as the entity possibly associated with stent-retriever device type was significantly less frequent in the group treated with the APH: 29.7\% for AP and 16.0\% for APH; p = 0.005; however, rates of symptomatic hemorrhage with clinical deterioration and in domo mortality were not statistically different. Neither the median number of stent-retriever passages needed to achieve final recanalization, time from groin puncture to first pass, time from groin puncture to final recanalization nor the number of cases in which successful recanalization could only be achieved by using a different stent-retriever as bail-out device differed between both groups. Conclusion In the specific example of the APERIO® stent-retriever device, we observed that further technological developments of the new generation device were not associated with disadvantages with respect to typical observational indicators of safety or effectiveness.}, language = {en} } @article{TonyBurmesterSchulzeKoopsetal.2011, author = {Tony, Hans-Peter and Burmester, Gerd and Schulze-Koops, Hendrik and Grunke, Mathias and Henes, Joerg and K{\"o}tter, Ina and Haas, Judith and Unger, Leonore and Lovric, Svjetlana and Haubitz, Marion and Fischer-Betz, Rebecca and Chehab, Gamal and Rubbert-Roth, Andrea and Specker, Christof and Weinerth, Jutta and Holle, Julia and M{\"u}ller-Ladner, Ulf and K{\"o}nig, Ramona and Fiehn, Christoph and Burgwinkel, Philip and Budde, Klemens and S{\"o}rensen, Helmut and Meurer, Michael and Aringer, Martin and Kieseier, Bernd and Erfurt-Berge, Cornelia and Sticherling, Michael and Veelken, Roland and Ziemann, Ulf and Strutz, Frank and von Wussow, Praxis and Meier, Florian MP and Hunzelmann, Nico and Schmidt, Enno and Bergner, Raoul and Schwarting, Andreas and Eming, R{\"u}diger and Schwarz-Eywill, Michael and Wassenberg, Siegfried and Fleck, Martin and Metzler, Claudia and Zettl, Uwe and Westphal, Jens and Heitmann, Stefan and Herzog, Anna L. and Wiendl, Heinz and Jakob, Waltraud and Schmidt, Elvira and Freivogel, Klaus and D{\"o}rner, Thomas and Hertl, Michael and Stadler, Rudolf}, title = {Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID)}, series = {Arthritis Research \& Therapy}, volume = {13}, journal = {Arthritis Research \& Therapy}, number = {R75}, doi = {10.1186/ar3337}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142856}, pages = {1-14}, year = {2011}, abstract = {Introduction: Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin's lymphoma in a real-life clinical setting. Methods: Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators. Results: A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0\% with systemic lupus erythematosus, 15.7\% antineutrophil cytoplasmic antibody-associated granulomatous vasculitides, 15.1\% multiple sclerosis and 10.0\% pemphigus) from 42 centres received a mean dose of 2,440 mg of rituximab over a median (range) of 194 (180 to 1,407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0\% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3\% of patients showed no response, 45.1\% showed a partial response and 41.6\% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician's visual analogue scale; mean improvement from baseline of 12.1 mm)}, language = {en} } @article{WurmbSchlerethKredeletal.2014, author = {Wurmb, Thomas Erik and Schlereth, Stefan and Kredel, Markus and Muellenbach, Ralf M. and Wunder, Christian and Brederlau, J{\"o}rg and Roewer, Norbert and Kenn, Werner and Kunze, Ekkehard}, title = {Routine Follow-Up Cranial Computed Tomography for Deeply Sedated, Intubated, and Ventilated Multiple Trauma Patients with Suspected Severe Head Injury}, series = {BioMed Research International}, journal = {BioMed Research International}, number = {361949}, doi = {10.1155/2014/361949}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120084}, year = {2014}, abstract = {Background. Missed or delayed detection of progressive neuronal damage after traumatic brain injury (TBI) may have negative impact on the outcome. We investigated whether routine follow-up CT is beneficial in sedated and mechanically ventilated trauma patients. Methods. The study design is a retrospective chart review. A routine follow-up cCT was performed 6 hours after the admission scan. We defined 2 groups of patients, group I: patients with equal or recurrent pathologies and group II: patients with new findings or progression of known pathologies. Results. A progression of intracranial injury was found in 63 patients (42\%) and 18 patients (12\%) had new findings in cCT 2 (group II). In group II a change in therapy was found in 44 out of 81 patients (54\%). 55 patients with progression or new findings on the second cCT had no clinical signs of neurological deterioration. Of those 24 patients (44\%) had therapeutic consequences due to the results of the follow-up cCT. Conclusion. We found new diagnosis or progression of intracranial pathology in 54\% of the patients. In 54\% of patients with new findings and progression of pathology, therapy was changed due to the results of follow-up cCT. In trauma patients who are sedated and ventilated for different reasons a routine follow-up CT is beneficial.}, language = {en} } @article{AlbertWeissenbergerMenclHoppetal.2014, author = {Albert-Weissenberger, Christiane and Mencl, Stine and Hopp, Sarah and Kleinschnitz, Christoph and Siren, Anna-Leena}, title = {Role of the kallikrein-kinin system in traumatic brain injury}, series = {Frontiers in Cellular Neuroscience}, volume = {8}, journal = {Frontiers in Cellular Neuroscience}, issn = {1662-5102}, doi = {10.3389/fncel.2014.00345}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-118226}, pages = {345}, year = {2014}, abstract = {Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide. Despite improvements in acute intensive care, there are currently no specific therapies to ameliorate the effects of TBI. Successful therapeutic strategies for TBI should target multiple pathophysiologic mechanisms that occur at different stages of brain injury. The kallikrein-kinin system is a promising therapeutic target for TBI as it mediates key pathologic events of traumatic brain damage, such as edema formation, inflammation, and thrombosis. Selective and specific kinin receptor antagonists and inhibitors of plasma kallikrein and coagulation factor XII have been developed, and have already shown therapeutic efficacy in animal models of stroke and TBI. However, conflicting preclinical evaluation, as well as limited and inconclusive data from clinical trials in TBI, suggests that caution should be taken before transferring observations made in animals to humans. This review summarizes current evidence on the pathologic significance of the kallikrein-kinin system during TBI in animal models and, where available, the experimental findings are compared with human data.}, language = {en} } @phdthesis{Subramanian2011, author = {Subramanian, Narayan}, title = {Role of NaV1.9 in activity dependent axon growth in embryonic cultured motoneurons}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-57536}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2011}, abstract = {Spontaneous neural activity has been shown to regulate crucial events in neurite growth including axonal branching and path finding. In animal models of spinal muscular atrophy (SMA) cultured embryonic mouse motoneurons show distinct defect in axon elongation and neural activity. This defect is governed by abnormal clustering of Ca2+ channels in the axonal regions and the protruding growth cone area. The mechanisms that regulate the opening of calcium channels in developing motoneurons are not yet clear. The question was addressed by blocking neural activity in embryonic cultured motoneurons by pharmacological inhibition of voltage-gated sodium channels (VGSC) by saxitoxin (STX) and tetrodotoxin (TTX). Low dosages of STX resulted in significant reduction of axon growth and neural activity in cultured motoneurons. This pharmacological treatment did not affect survival of motoneurons in comparison to control motoneurons that was grown in the presence of survival neurotrophic factors BDNF and CNTF. It was also found that STX was 10 times more potent than TTX a common inhibitor of VGSC with a reduced activity on the TTX-insensitive sodium channels NaV1.5, NaV1.8 and NaV1.9. Reverse Transcriptase-PCR experiments revealed the presence of NaV1.9 as the likely candidate that begins to express from embryonic stage sixteen in the mouse spinal cord. Immunolabelling experiments showed that the channel is expressed in the axonal compartments and axonal growth cones in cultured motoneurons. Suppression of NaV1.9 in cultured motoneurons by lentivirus mediated short hairpin-RNA (shRNA) resulted in shorter axon length in comparison with uninfected and scrambled constructs. Further, embryonic motoneurons cultured from NaV1.9 knockout mice also showed a significant reduction in neural activity and axon growth. The findings of this work highlight the role of NaV1.9 as an important contender in regulating activity dependent axon growth in embryonic cultured motoneurons. NaV1.9 could therefore be considered as a prospective molecule that could play an important role in regulating axon growth in motoneuron disease models like spinal muscular atrophy (SMA).}, subject = {Axon}, language = {en} } @phdthesis{KronerMilsch2008, author = {Kroner-Milsch, Antje}, title = {Role of immune cells in hereditary myelinopathies}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-28976}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2008}, abstract = {Myelin mutations in the central and peripheral nervous system lead to severely disabling, currently untreatable diseases. In this study, we used transgenic PLP overexpressing mice (PLPtg) as a model for central inherited myelinopathies, such as leukodystrophies, and heterozygously P0 deficient (P0+/-) mice as models for peripheral hereditary polyneuropathies. Both models are characterized by low grade nervous tissue inflammation. Macrophages and CD8+ T- lymphocytes contribute to the myelin pathology as shown by crossbreeding experiments with immunodeficient mice. Having shown the relevance of CD8+ T- lymphocytes in PLPtg mice, we investigated the influence of one major cytotoxic molecule (granzyme B) on neural damage. By generation of granzyme B deficient PLPtg bone marrow chimeras, we could demonstrate a reduction of myelin pathology and oligodendrocyte death. Taken together, granzyme B is at least partly responsible for the cytotoxicity induced neural damage in PLPtg mice. To further explore the role of immune modulation, we focussed on the influence of the coinhibitory molecule PD-1, a CD28-related receptor expressed on activated T- and B-lymphocytes. By investigating myelin mutants of the CNS and PNS (PLPtg and P0+/-) with an additional PD-1 deficiency, induced by crossbreeding or bone marrow chimerization, we found a significant increase of CD8+ T- lymphocytes and massive increase of the myelin pathology in both the CNS and PNS model. In PLPtg mice, absence of PD-1 increased oligodendrocyte apoptosis, clonal expansions and a higher propensity of CNS but not peripheral CD8+ T- cells to secrete proinflammatory cytokines. In P0+/- mice, absence of PD-1 lead to moderate motor and sensory disturbances, confirming the important role of PD-1 in immune homeostasis. Taken together, we identified granzyme B as an important effector agent of cytotoxic T-lymphocytes in PLPtg mice and PD-1 as a crucial player in regulating the effector cells in our models of central and peripheral myelinopathy. Alterations of this regulatory pathway lead to overt neuroinflammation of high pathogenetic impact. These results might help to understand mechanisms responsible for high clinical variability of polygenic or even monogenic disorders of the nervous system.}, subject = {Myelinopathie}, language = {en} } @article{HaeuserWalittFitzcharlesetal.2014, author = {H{\"a}user, Winfried and Walitt, Brian and Fitzcharles, Mary-Ann and Sommer, Claudia}, title = {Review of pharmacological therapies in fibromyalgia syndrome}, series = {Arthritis Research \& Therapy}, volume = {16}, journal = {Arthritis Research \& Therapy}, number = {201}, issn = {1465-9913}, doi = {10.1186/ar4441}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121598}, year = {2014}, abstract = {This review addresses the current status of drug therapy for the management of fibromyalgia syndrome (FMS) and is based on interdisciplinary FMS management guidelines, meta-analyses of drug trial data, and observational studies. In the absence of a single gold-standard medication, patients are treated with a variety of drugs from different categories, often with limited evidence. Drug therapy is not mandatory for the management of FMS. Pregabalin, duloxetine, milnacipran, and amitriptyline are the current first-line prescribed agents but have had a mostly modest effect. With only a minority of patients expected to experience substantial benefit, most will discontinue therapy because of either a lack of efficacy or tolerability problems. Many drug treatments have undergone limited study and have had negative results. It is unlikely that these failed pilot trials will undergo future study. However, medications, though imperfect, will continue to be a component of treatment strategy for these patients. Both the potential for medication therapy to relieve symptoms and the potential to cause harm should be carefully considered in their administration.}, language = {en} } @article{AsterRomanosWalitzaetal.2022, author = {Aster, Hans-Christoph and Romanos, Marcel and Walitza, Susanne and Gerlach, Manfred and M{\"u}hlberger, Andreas and Rizzo, Albert and Andreatta, Marta and Hasenauer, Natalie and Hartrampf, Philipp E. and Nerlich, Kai and Reiners, Christoph and Lorenz, Reinhard and Buck, Andreas K. and Deserno, Lorenz}, title = {Responsivity of the striatal dopamine system to methylphenidate — A within-subject I-123-β-CIT-SPECT study in male children and adolescents with attention-deficit/hyperactivity disorder}, series = {Frontiers in Psychiatry}, volume = {13}, journal = {Frontiers in Psychiatry}, issn = {1664-0640}, doi = {10.3389/fpsyt.2022.804730}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270862}, year = {2022}, abstract = {Background: Methylphenidate (MPH) is the first-line pharmacological treatment of attention-deficit/hyperactivity disorder (ADHD). MPH binds to the dopamine (DA) transporter (DAT), which has high density in the striatum. Assessments of the striatal dopamine transporter by single positron emission computed tomography (SPECT) in childhood and adolescent patients are rare but can provide insight on how the effects of MPH affect DAT availability. The aim of our within-subject study was to investigate the effect of MPH on DAT availability and how responsivity to MPH in DAT availability is linked to clinical symptoms and cognitive functioning. Methods Thirteen adolescent male patients (9-16 years) with a diagnosis of ADHD according to the DSM-IV and long-term stimulant medication (for at least 6 months) with MPH were assessed twice within 7 days using SPECT after application of I-123-β-CIT to examine DAT binding potential (DAT BP). SPECT measures took place in an on- and off-MPH status balanced for order across participants. A virtual reality continuous performance test was performed at each time point. Further clinical symptoms were assessed for baseline off-MPH. Results On-MPH status was associated with a highly significant change (-29.9\%) of striatal DAT BP as compared to off-MPH (t = -4.12, p = 0.002). A more pronounced change in striatal DAT BP was associated with higher off-MPH attentional and externalizing symptom ratings (Pearson r = 0.68, p = 0.01). Striatal DAT BP off-MPH, but not on-MPH, was associated with higher symptom ratings (Pearson r = 0.56, p = 0.04). Conclusion Our findings corroborate previous reports from mainly adult samples that MPH changes striatal DAT BP availability and suggest higher off-MPH DAT BP, likely reflecting low baseline DA levels, as a marker of symptom severity.}, language = {en} } @article{KornKleinschnitzMagnusetal.2016, author = {Korn, Thomas and Kleinschnitz, Christoph and Magnus, Tim and Meuth, Sven G. and Linker, Ralf A.}, title = {Report on the 7th scientific meeting of the Association for the Advancement of Young Academics in Neurology (NEUROWIND e.V.) held in Motzen, Germany, October 30-November 1, 2015}, series = {Experimental and Translational Stroke Medicine}, volume = {8}, journal = {Experimental and Translational Stroke Medicine}, number = {3}, organization = {7th NEUROWIND e.V. scientific meeting}, doi = {10.1186/s13231-016-0017-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146595}, year = {2016}, abstract = {From October 30-November 1, 2015, the 7th NEUROWIND e.V. meeting was held in Motzen, Brandenburg, Germany. Seventy doctoral students and postdocs from over 25 different groups working in German and Swiss University Hospitals or Research Institutes attended the meeting to discuss their latest experiments and findings in the fields of neuroimmunology, neurodegeneration and neurovascular research. This meeting report summarizes the many diverse presentations and the new preclinical to clinical neurology research data that were shared by the participants at the meeting.}, language = {en} } @article{KleinschnitzLinkerMagnusetal.2015, author = {Kleinschnitz, Christoph and Linker, Ralf A. and Magnus, Tim and Korn, Thomas and Meuth, Sven G.}, title = {Report on the 6th scientific meeting of the "Verein zur F{\"o}rderung des Wissenschaftlichen Nachwuchses in der Neurologie" (NEUROWIND e.V.) held in Motzen, Germany, Oct. 31th - Nov. 2nd, 2014}, series = {Experimental \& Translational Stroke Medicine}, volume = {7}, journal = {Experimental \& Translational Stroke Medicine}, number = {1}, organization = {on behalf of the speakers at the 6'th NEUROWIND e.V. scientific meeting}, doi = {10.1186/s13231-014-0013-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125049}, year = {2015}, abstract = {From October 31th - November 2nd, 2014, the 6th NEUROWIND e.V. meeting was held in Motzen, Brandenburg, Germany. 70 doctoral students and postdocs from over 25 different groups working in German and Swiss university hospitals or research institutes attended the meeting to discuss their latest experiments and findings in the fields of neuroimmunology, neurodegeneration and neurovascular research. The meeting was regarded as a very well organized platform to support research of young investigators in Germany and all participants enjoyed the stimulating environment for lively in depth discussions. According to the major aim of NEUROWIND e.V. to support younger researchers in Germany the 4th NEUROWIND YOUNG SCIENTIST AWARD for experimental neurology was awarded to Michael Breckwoldt on his work in the group of Thomas Misgeld (Institute of Neuronal Cell Biology, Technische Universit{\"a}t M{\"u}nchen, Germany). The successful project was published in Nature Medicine entitled "Multiparametric optical analysis of mitochondrial redox signals during neuronal physiology and pathology in vivo". This outstanding paper deals with a molecular imaging approach in living mice to optically analyze the role of mitochondrial redox signals in axons in health and disease. The award is endowed with 20.000 Euro sponsored by Merck Serono GmbH, Darmstadt, Germany (unrestricted educational grant). This year's keynote lecture was given by Bernhard Hemmer, Head of the Department of Neurology at the Klinikum rechts der Isar, Technische Universit{\"a}t M{\"u}nchen. Dr. Hemmer highlighted the particular role of B cells and (auto)antibodies in multiple sclerosis (MS). As a new highlight Dr. Urbahns, head of global discovery technologies at Merck research laboratories, gave insights from research practice in the pharmaceutical industry and introduced a shift in the view on present-day drug discovery paradigms.}, language = {en} } @article{LinkerMagnusKornetal.2013, author = {Linker, Ralf A. and Magnus, Tim and Korn, Thomas and Kleinschnitz, Christoph and Meuth, Sven G.}, title = {Report on the 5'th scientific meeting of the "Verein zur F{\"o}rderung des Wissenschaftlichen Nachwuchses in der Neurologie" (NEUROWIND e.V.) held in Motzen, Germany, Oct. 25th - Oct. 27th, 2013}, series = {Experimental \& Translational Stroke Medicine}, volume = {5}, journal = {Experimental \& Translational Stroke Medicine}, number = {15}, doi = {10.1186/2040-7378-5-15}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-129230}, year = {2013}, abstract = {From october 25th - 27th 2013, the 5th NEUROWIND e.V. meeting was held in Motzen, Brandenburg, Germany. This year more than 60 doctoral students and postdocs from over 25 different groups working in German university hospitals or research institutes attended the meeting to discuss their latest findings in the fields of neuroimmunology, neurodegeneration and neurovascular research. All participants appreciated the stimulating environment in Motzen, Brandenburg, and people took the opportunity for scientific exchange, discussion about ongoing projects and already started further collaborations. Like in the previous years, the symposium was regarded as a very well organized platform to support research of young investigators in Germany. According to the major aim of NEUROWIND e.V. to support younger researchers in Germany the 3rd NEUROWIND YOUNG SCIENTIST AWARD for experimental neurology was awarded to Ruth Stassart working in the group of Klaus Armin Nave and Wolfgang Br{\"u}ck (MPI G{\"o}ttingen and Department of Neuropathology, G{\"o}ttingen Germany). The successful work was published in Nature Neuroscience entitled "A role for Swann cell-derived neuregulin-1 in remyelination". This outstanding paper deals with the function of Schwann cell neuregulin as an endogenous factor for myelin repair. The award is endowed with 20.000 Euro sponsored by Merck Serono GmbH, Darmstadt, Germany (unrestricted educational grant). This year's keynote lecture was given by Albert Ludolph, Head of the Department of Neurology at the University Clinic of Ulm. Dr. Ludolph highlighted the particular role of individual scientists for the development of research concepts in Alzheimer´s disease (AD) and frontotemporal dementia (FTD).}, language = {en} } @techreport{LinkerMeuthMagnusetal.2012, author = {Linker, Ralf, A. and Meuth, Sven G. and Magnus, Tim and Korn, Thomas and Kleinschnitz, Christoph}, title = {Report on the 4'th scientific meeting of the "Verein zur F{\"o}rderung des Wissenschaftlichen Nachwuchses in der Neurologie" (NEUROWIND e.V.) held in Motzen, Germany, Nov. 2'nd - Nov. 4'th, 2012 [meeting report]}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-76407}, year = {2012}, abstract = {From November 2nd - 4th 2012, the 4th NEUROWIND e.V. meeting was held in Motzen, Brandenburg, Germany. Again more than 60 participants, predominantly at the doctoral student or postdoc level, gathered to share their latest findings in the fields of neurovascular research, neurodegeneration and neuroinflammation. Like in the previous years, the symposium provided an excellent platform for scientific exchange and the presentation of innovative projects in the stimulating surroundings of the Brandenburg outback. This year's keynote lecture on the pathophysiological relevance of neuronal networks was given by Christian Gerloff, Head of the Department of Neurology at the University Clinic of Hamburg-Eppendorf. Another highlight of the meeting was the awarding of the NEUROWIND e.V. prize for young scientists working in the field of experimental neurology. The award is donated by the Merck Serono GmbH, Darmstadt, Germany and is endowed with 20.000 Euro. This year the jury decided unanimously to adjudge the award to Michael Gliem from the Department of Neurology at the University Clinic of D{\"u}sseldorf (group of Sebastian Jander), Germany, for his outstanding work on different macrophage subsets in the pathogenesis of ischemic stroke published in the Annals of Neurology in 2012.}, subject = {Medizin}, language = {en} } @article{KleinschnitzMeuthMagnusetal.2012, author = {Kleinschnitz, Christph and Meuth, Sven G. and Magnus, Tim and Korn, Thomas and Linker, Ralf A.}, title = {Report on the 3'rd scientific meeting of the "Verein zur F{\"o}rderung des Wissenschaftlichen Nachwuchses in der Neurologie" (NEUROWIND e.V.) held in Motzen, Germany, Nov. 4'th - Nov. 6'th, 2011}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75388}, year = {2012}, abstract = {From November 4th- 6th 2011, the 3rd NEUROWIND e.V. meeting was held in Motzen, Brandenburg, Germany. Like in the previous years, the meeting provided an excellent platform for scientific exchange and the presentation of innovative projects for young colleagues in the fields of neurovascular research, neuroinflammation and neurodegeneration. As kick-off to the scientific sessions, Reinhard Hohlfeld, Head of the Institute for Clinical Neuroimmunology in Munich, gave an illustrious overview on the many fascinations of neuroimmunologic research. A particular highlight on the second day of the meeting was the award of the 1'st NEUROWIND e.V. prize for young academics in the field of experimental neurology. This award is posted for young colleagues under the age of 35 with a significant achievement in the field of neurovascular research, neuroinflammation or neurodegeneration and comprises an amount of 20.000 Euro, founded by Merck Serono GmbH, Darmstadt. Germany. The first prize was awarded to Ivana Nikic from Martin Kerschensteiner's group in Munich for her brilliant work on a reversible form of axon damage in experimental autoimmune encephalomyelitis and multiple sclerosis, published in Nature Medicine in 2011. This first prize award ceremony was a great incentive for the next call for proposals now upcoming in 2012.}, subject = {Medizin}, language = {en} } @techreport{MagnusLinkerMeuthetal.2011, author = {Magnus, Tim and Linker, Ralf A. and Meuth, Sven G. and Kleinschnitz, Christoph and Korn, Thomas}, title = {Report on the 2nd scientific meeting of the "Verein zur Foerderung des Wissenschaftlichen Nachwuchses in der Neurologie" (NEUROWIND e.V.) held in Motzen, Germany, Oct. 29'th - Oct. 31'st, 2010}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68789}, year = {2011}, abstract = {Summary of the scientific contributions to the NEUROWIND meeting 2010: Contributions in the fields of neuroimmunology and neurodegeneration}, subject = {Wissenschaftlicher Nachwuchs}, language = {en} }