@phdthesis{Reymann2016,
  author    = {Reymann, Stephan Andreas},
  title     = {Pathophysiologische Rolle und therapeutische Relevanz von Plasmakallikrein beim experimentellen Schlaganfall},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-135834},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2016},
  abstract  = {Die Rolle thromboinflammatorischer Vorg{\"a}nge in der Pathogenese des isch{\"a}mischen Schlaganfalls ist in den letzten Jahren immer mehr in den wissenschaftlichen Fokus ger{\"u}ckt. Plasmakallikrein (PK) spaltet von hochmolekularem Kininogen (KNG) Bradykinin (BK) ab und ist dadurch Ausgangspunkt des proinflammatorischen Kallikrein-Kinin-Systems (KKS). Zum anderen kann es den Gerinnungsfaktor XII (FXII) aktivieren, den Ausgangspunkt der intrinsischen Gerinnungskaskade. Es initiiert also sowohl inflammatorische als auch thrombotische Vorg{\"a}nge. Daher wurde in dieser Arbeit der Effekt einer Blockade PKs in einem Mausmodell der fokalen zerebralen Isch{\"a}mie untersucht - und zwar sowohl durch genetische Depletion als auch durch pharmakologische Blockade. Beide Ans{\"a}tze brachten einen nachhaltigen protektiven Effekt in Bezug auf Infarktgr{\"o}ßen und funktionelles Outcome, ohne die Blutungsgefahr zu erh{\"o}hen.},
  subject      = {Plasmakallikrein},
  language  = {de}
}
@article{HornBaumannPereiraetal.2012,
  author    = {Horn, Michael and Baumann, Reto and Pereira, Jorge A. and Sidiropoulos, P{\´a}ris N. M. and Somandin, Christian and Welzl, Hans and Stendel, Claudia and L{\"u}hmann, Tessa and Wessig, Carsten and Toyka, Klaus V. and Relvas, Jo{\~a}o B. and Senderek, Jan and Suter, Ueli},
  title     = {Myelin is dependent on the Charcot-Marie-Tooth Type 4H disease culprit protein FRABIN/FGD4 in Schwann cells},
  series = {Brain},
  volume    = {135},
  journal   = {Brain},
  doi       = {10.1093/brain/aws275},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125390},
  pages     = {3567-3583},
  year      = {2012},
  abstract  = {Studying the function and malfunction of genes and proteins associated with inherited forms of peripheral neuropathies has provided multiple clues to our understanding of myelinated nerves in health and disease. Here, we have generated a mouse model for the peripheral neuropathy Charcot-Marie-Tooth disease type 4H by constitutively disrupting the mouse orthologue of the suspected culprit gene FGD4 that encodes the small RhoGTPase Cdc42-guanine nucleotide exchange factor Frabin. Lack of Frabin/Fgd4 causes dysmyelination in mice in early peripheral nerve development, followed by profound myelin abnormalities and demyelination at later stages. At the age of 60 weeks, this was accompanied by electrophysiological deficits. By crossing mice carrying alleles of Frabin/Fgd4 flanked by loxP sequences with animals expressing Cre recombinase in a cell type-specific manner, we show that Schwann cell-autonomous Frabin/Fgd4 function is essential for proper myelination without detectable primary contributions from neurons. Deletion of Frabin/Fgd4 in Schwann cells of fully myelinated nerve fibres revealed that this protein is not only required for correct nerve development but also for accurate myelin maintenance. Moreover, we established that correct activation of Cdc42 is dependent on Frabin/Fgd4 function in healthy peripheral nerves. Genetic disruption of Cdc42 in Schwann cells of adult myelinated nerves resulted in myelin alterations similar to those observed in Frabin/Fgd4-deficient mice, indicating that Cdc42 and the Frabin/Fgd4-Cdc42 axis are critical for myelin homeostasis. In line with known regulatory roles of Cdc42, we found that Frabin/Fgd4 regulates Schwann cell endocytosis, a process that is increasingly recognized as a relevant mechanism in peripheral nerve pathophysiology. Taken together, our results indicate that regulation of Cdc42 by Frabin/Fgd4 in Schwann cells is critical for the structure and function of the peripheral nervous system. In particular, this regulatory link is continuously required in adult fully myelinated nerve fibres. Thus, mechanisms regulated by Frabin/Fgd4-Cdc42 are promising targets that can help to identify additional regulators of myelin development and homeostasis, which may crucially contribute also to malfunctions in different types of peripheral neuropathies.},
  language  = {en}
}
@article{GolombeckWessigMonoranuetal.2013,
  author    = {Golombeck, Stefanie Kristin and Wessig, Carsten and Monoranu, Camelia-Maria and Sch{\"u}tz, Ansgar and Solymosi, Laszlo and Melzer, Nico and Kleinschnitz, Christoph},
  title     = {Fatal atypical reversible posterior leukoencephalopathy syndrome: a case report},
  series = {Journal of Medical Case Reports},
  volume    = {7},
  journal   = {Journal of Medical Case Reports},
  number    = {14},
  doi       = {10.1186/1752-1947-7-14},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-135517},
  year      = {2013},
  abstract  = {Introduction: Reversible posterior leukoencephalopathy syndrome - a reversible subacute global encephalopathy clinically presenting with headache, altered mental status, visual symptoms such as hemianopsia or cortical blindness, motor symptoms, and focal or generalized seizures - is characterized by a subcortical vasogenic edema symmetrically affecting posterior brain regions. Complete reversibility of both clinical signs and magnetic resonance imaging lesions is regarded as a defining feature of reversible posterior leukoencephalopathy syndrome. Reversible posterior leukoencephalopathy syndrome is almost exclusively seen in the setting of a predisposing clinical condition, such as pre-eclampsia, systemic infections, sepsis and shock, certain autoimmune diseases, various malignancies and cytotoxic chemotherapy, transplantation and concomitant immunosuppression (especially with calcineurin inhibitors) as well as episodes of abrupt hypertension. We describe for the first time clinical, radiological and histological findings in a case of reversible posterior leukoencephalopathy syndrome with an irreversible and fatal outcome occurring in the absence of any of the known predisposing clinical conditions except for a hypertensive episode. Case presentation: A 58-year-old Caucasian woman presented with a two-week history of subacute and progressive occipital headache, blurred vision and imbalance of gait and with no evidence for raised arterial blood pressure during the two weeks previous to admission. Her past medical history was unremarkable except for controlled arterial hypertension. Cerebral magnetic resonance imaging demonstrated cortical and subcortical lesions with combined vasogenic and cytotoxic edema atypical for both venous congestion and arterial infarction. Routine laboratory and cerebrospinal fluid parameters were normal. The diagnosis of reversible posterior leukoencephalopathy syndrome was established. Within hours after admission the patient showed a rapidly decreasing level of consciousness, extension and flexion synergisms, bilaterally extensor plantar responses and rapid cardiopulmonary decompensation requiring ventilatory and cardiocirculatory support. Follow-up cerebral imaging demonstrated widespread and confluent cytotoxic edematous lesions in different arterial territories, global cerebral swelling, and subsequent upper and lower brainstem herniation. Four days after admission, the patient was declared dead because of brain death. Conclusion: This case demonstrates that fulminant and fatal reversible posterior leukoencephalopathy syndrome may occur spontaneously, that is, in the absence of any of the known predisposing systemic conditions.},
  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-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{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}
}
@phdthesis{Hullin2016,
  author    = {Hullin, Marcus},
  title     = {Zusammenhang zwischen Raumwahrnehmung, K{\"o}rperselbstgef{\"u}hl und Puppenhandillusion bei gesunden {\"A}lteren und Patienten mit kortikobasalem Syndrom},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134291},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2016},
  abstract  = {Das K{\"o}rperselbstgef{\"u}hl (KSG) bezeichnet das Gef{\"u}hl, einen bestimmten K{\"o}r-perteil als dem eigenen K{\"o}rper zugeh{\"o}rig zu empfinden. Es erscheint stabil und nicht st{\"o}rbar, l{\"a}sst sich jedoch bei den meisten Menschen experimentell beein-flussen. Ein Beispiel hierf{\"u}r ist die Puppenhandillusion (PHI), bei der die nicht sichtbare eigene Hand des Probanden und eine sichtbare Plastikhand in glei-cher Stellung an den gleichen Fingerstellen synchron mit zwei Pinseln bestri-chen wird, wodurch die Wahrnehmung entsteht, die Plastikhand sei die eigene. Ver{\"a}nderungen des KSG k{\"o}nnen jedoch auch im Rahmen neurodegenerativer Erkrankungen vorkommen. So nimmt beim kortikobasalen Syndrom (CBS) etwa die H{\"a}lfte der Patienten im Krankheitsverlauf einen Arm und seine Bewegungen als fremd war ("Alien-limb"-Ph{\"a}nomen). Das CBS beginnt oft einseitig und ist durch eine rasch fortschreitende, akinetisch-rigide Parkinson-Symptomatik, aber auch durch kortikale Funktionsst{\"o}rungen gekennzeichnet, so dass es ne-ben einer St{\"o}rung des KSG auch zu einer St{\"o}rung der r{\"a}umlichen Aufmerk-samkeit (Hemineglect) kommt. Bislang wurde der Zusammenhang zwischen Raumwahrnehmung, KSG und PHI bei gesunden {\"a}lteren Menschen noch nicht systematisch untersucht. Ebenso wenig war bisher bekannt, inwieweit das KSG bei CBS-Patienten durch die PHI modulierbar ist. Wir untersuchten 65 gesunde {\"a}ltere Probanden (60 - 90 Jahre) ohne neurologi-sche Vorerkrankungen sowie zehn Patienten zwischen 59 und 77 Jahren mit wahrscheinlichem oder m{\"o}glichem CBS. Den kognitiven und orientierend seeli-schen Zustand eruierten wir mit Hilfe des PANDA- und des Uhrentests, die Raumwahrnehmung testeten wir mittels des Milner-Landmark-Tests sowie des Letter-Cancellation-Tests, das spontane K{\"o}rperselbstgef{\"u}hl wurde mittels eines Fragebogens erfasst. Der PHI-Versuch wurde mit synchroner sowie asynchro-ner taktiler Stimulation durchgef{\"u}hrt, das Auftreten eines Selbstgef{\"u}hls f{\"u}r die Plastikhand wurde subjektiv {\"u}ber spontane {\"A}ußerungen und einen etablierten Fragebogen, objektiv {\"u}ber den sog. propriozeptiven Drift der stimulierten Hand erfasst. Unter den Kontrollprobanden fanden sich 12\% mit einer wahrscheinlichen De-menz, wohingegen dies bei 80\% der CBS-Patienten der Fall war. Im Milner-Landmark-Test zeigte sich bei den Kontrollprobanden eine {\"U}bersch{\"a}tzung des rechten Segmentes einer mittig geteilten Linie, entsprechend einem milden Hemineglect, bei den CBS-Patienten konnte keine einheitliche Tendenz festge-stellt werden. Das spontane K{\"o}rperselbstgef{\"u}hl stellte sich bei nahezu allen Probanden als intakt dar, w{\"a}hrend sich bei vier Patienten mit CBS Hinweise auf aktuelle oder intermittierende St{\"o}rungen desselben ergaben. Die Puppenhandil-lusion war in der Gruppe gesunder {\"A}lterer bei synchroner Stimulation ausl{\"o}s-bar, nicht jedoch bei asynchroner Stimulation. Eine Lateralisierungstendenz zeigte sich nicht. Dar{\"u}ber hinaus konnte bei den Probanden eine positive Korre-lation zwischen dem propriozeptiven Drift der linken Hand nach synchroner Stimulation und dem Hemineglect nach links gefunden werden. Bei den CBS-Patienten fand sich unabh{\"a}ngig von der Stimulationsart (synchron oder asyn-chron) eine erh{\"o}hte Bereitschaft, die linke Puppenhand ins eigene K{\"o}rperbild zu integrieren. Das Auftreten der PHI bei gesunden {\"a}lteren Probanden ist vergleichbar mit den Daten j{\"u}ngerer Probandengruppen. Hinweise auf eine hemisph{\"a}rische Laterali-sierungstendenz der PHI ergaben sich nicht, jedoch scheint der in dieser Grup-pe festgestellte leichtgradige Hemineglect nach links den multisensorischen Prozess zu beeinflussen, eine k{\"u}nstliche Hand in das eigene K{\"o}rperschema zu integrieren. Bei den CBS-Patienten war die PHI unabh{\"a}ngig vom Stimulations-modus links besser ausl{\"o}sbar als rechts, was mit vorwiegend rechtshemisph{\"a}-rischen krankheitsbedingten Ver{\"a}nderungen des multisensorischen Integrati-onsprozesses vereinbar ist.},
  subject      = {Raumwahrnehmung},
  language  = {de}
}
@article{VolkmannAlbaneseAntoninietal.2013,
  author    = {Volkmann, Jens and Albanese, Alberto and Antonini, Angelo and Chaudhuri, K. Ray and Clarke, Karl E. and de Bie, Rob M. A. and Deuschl, G{\"u}nther and Eggert, Karla and Houeto, Jean-Luc and Kulisevsky, Jaime and Nyholm, Dag and Odin, Per and Ostergaard, Karen and Poewe, Werner and Pollak, Pierre and Rabey, Jose Martin and Rascol, Olivier and Ruzicka, Evzen and Samuel, Michael and Speelman, Hans and Sydow, Olof and Valldeoriola, Francesc and van der Linden, Chris and Oertel, Wolfgang},
  title     = {Selecting deep brain stimulation or infusion therapies in advanced Parkinson's disease: an evidence-based review},
  series = {Journal of Neurology},
  volume    = {260},
  journal   = {Journal of Neurology},
  doi       = {10.1007/s00415-012-6798-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132373},
  pages     = {2701-2714},
  year      = {2013},
  abstract  = {Motor complications in Parkinson's disease (PD) result from the short half-life and irregular plasma fluctuations of oral levodopa. When strategies of providing more continuous dopaminergic stimulation by adjusting oral medication fail, patients may be candidates for one of three device-aided therapies: deep brain stimulation (DBS), continuous subcutaneous apomorphine infusion, or continuous duodenal/jejunal levodopa/carbidopa pump infusion (DLI). These therapies differ in their invasiveness, side-effect profile, and the need for nursing care. So far, very few comparative studies have evaluated the efficacy of the three device-aided therapies for specific motor problems in advanced PD. As a result, neurologists currently lack guidance as to which therapy could be most appropriate for a particular PD patient. A group of experts knowledgeable in all three therapies reviewed the currently available literature for each treatment and identified variables of clinical relevance for choosing one of the three options such as type of motor problems, age, and cognitive and psychiatric status. For each scenario, pragmatic and (if available) evidence-based recommendations are provided as to which patients could be candidates for either DBS, DLI, or subcutaneous apomorphine.},
  language  = {en}
}
@article{GolombeckWessigMonoranuetal.2013,
  author    = {Golombeck, Stefanie Kristin and Wessig, Carsten and Monoranu, Camelia-Maria and Sch{\"u}tz, Ansgar and Solymosi, Laszlo and Melzer, Niko and Kleinschnitz, Christoph},
  title     = {Fatal atypical reversible posterior leukoencephalopathy syndrome: a case report},
  series = {Journal of Medical Case Reports},
  volume    = {7},
  journal   = {Journal of Medical Case Reports},
  number    = {14},
  doi       = {10.1186/1752-1947-7-14},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-129456},
  year      = {2013},
  abstract  = {Introduction: Reversible posterior leukoencephalopathy syndrome - a reversible subacute global encephalopathy clinically presenting with headache, altered mental status, visual symptoms such as hemianopsia or cortical blindness, motor symptoms, and focal or generalized seizures - is characterized by a subcortical vasogenic edema symmetrically affecting posterior brain regions. Complete reversibility of both clinical signs and magnetic resonance imaging lesions is regarded as a defining feature of reversible posterior leukoencephalopathy syndrome. Reversible posterior leukoencephalopathy syndrome is almost exclusively seen in the setting of a predisposing clinical condition, such as pre-eclampsia, systemic infections, sepsis and shock, certain autoimmune diseases, various malignancies and cytotoxic chemotherapy, transplantation and concomitant immunosuppression (especially with calcineurin inhibitors) as well as episodes of abrupt hypertension. We describe for the first time clinical, radiological and histological findings in a case of reversible posterior leukoencephalopathy syndrome with an irreversible and fatal outcome occurring in the absence of any of the known predisposing clinical conditions except for a hypertensive episode. Case presentation: A 58-year-old Caucasian woman presented with a two-week history of subacute and progressive occipital headache, blurred vision and imbalance of gait and with no evidence for raised arterial blood pressure during the two weeks previous to admission. Her past medical history was unremarkable except for controlled arterial hypertension. Cerebral magnetic resonance imaging demonstrated cortical and subcortical lesions with combined vasogenic and cytotoxic edema atypical for both venous congestion and arterial infarction. Routine laboratory and cerebrospinal fluid parameters were normal. The diagnosis of reversible posterior leukoencephalopathy syndrome was established. Within hours after admission the patient showed a rapidly decreasing level of consciousness, extension and flexion synergisms, bilaterally extensor plantar responses and rapid cardiopulmonary decompensation requiring ventilatory and cardiocirculatory support. Follow-up cerebral imaging demonstrated widespread and confluent cytotoxic edematous lesions in different arterial territories, global cerebral swelling, and subsequent upper and lower brainstem herniation. Four days after admission, the patient was declared dead because of brain death. Conclusion: This case demonstrates that fulminant and fatal reversible posterior leukoencephalopathy syndrome may occur spontaneously, that is, in the absence of any of the known predisposing systemic conditions.},
  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}
}
@phdthesis{Oehler2015,
  author    = {Oehler, Steffen Claus},
  title     = {Deeskalation der Immuntherapie bei Patienten mit Multipler Sklerose},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133666},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2015},
  abstract  = {Die vorliegende Arbeit ist die erste, die sich mit der Frage besch{\"a}ftigt, mit welcher zur Deeskalation eingesetzten Therapie nach Beendigung einer Eskalationstherapie mit Mitoxantron am besten Krankheitsstabilit{\"a}t erreicht werden kann bzw. ob Patienten-/Krankheitscharakteristika existieren, die eine bestimmte Nachfolge-Therapie favorisieren. Trotz neuer Behandlungsm{\"o}glichkeiten der hochaktiven MS mit Fingolimod, Natalizumab und Alemtuzumab hat Mitoxantron im klinischen Alltag nach wie vor einen hohen Stellenwert, so dass die Fragestellung dieser Studie weiter relevant ist. Es zeigten sich keine Patientencharakteristika, die auf eine erfolgsversprechende Therapie in der Deeskalationsphase nach Mitoxantron schließen ließen. Bei Patienten, bei denen w{\"a}hrend der Eskalation mit Mitoxantron die Dosis reduziert werden konnte, wurden w{\"a}hrend der Deeskalationstherapie ein stabilerer Verlauf und weniger Therapiewechsel beobachtet. Bei Patienten, die wegen einer rein chronischen Krankheitsprogredienz eskaliert wurden, trat eine Verschlechterung nach Deeskalation h{\"a}ufiger auf als bei denjenigen, welche wegen Schubaktivit{\"a}t eskaliert wurden. Die Aussagekraft der Daten wird durch die nur niedrige Anzahl der in diese Studie eingeschlossenen Patienten limitiert. Rekrutierungsprobleme stellten die Hauptursache f{\"u}r die geringe Anzahl der Studienteilnehmer dar.},
  subject      = {Multiple Sklerose},
  language  = {de}
}