@article{GeisWeishauptGruenewaldetal.2011,
  author    = {Geis, Christian and Weishaupt, Andreas and Gr{\"u}newald, Benedikt and Wultsch, Thomas and Reif, Andreas and Gerlach, Manfred and Dirkx, Ron and Solimena, Michele and Perani, Daniela and Heckmann, Manfred and Toyka, Klaus V. and Folli, Franco and Sommer, Claudia},
  title     = {Human Stiff-Person Syndrome IgG Induces Anxious Behavior in Rats},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-74757},
  year      = {2011},
  abstract  = {Background: Anxiety is a heterogeneous behavioral domain playing a role in a variety of neuropsychiatric diseases. While anxiety is the cardinal symptom in disorders such as panic disorder, co-morbid anxious behavior can occur in a variety of diseases. Stiff person syndrome (SPS) is a CNS disorder characterized by increased muscle tone and prominent agoraphobia and anxiety. Most patients have high-titer antibodies against glutamate decarboxylase (GAD) 65. The pathogenic role of these autoantibodies is unclear. Methodology/Principal Findings: We re-investigated a 53 year old woman with SPS and profound anxiety for GABA-A receptor binding in the amygdala with (11)C-flumazenil PET scan and studied the potential pathogenic role of purified IgG from her plasma filtrates containing high-titer antibodies against GAD 65. We passively transferred the IgG fraction intrathecally into rats and analyzed the effects using behavioral and in vivo electrophysiological methods. In cell culture, we measured the effect of patient IgG on GABA release from hippocampal neurons. Repetitive intrathecal application of purified patient IgG in rats resulted in an anxious phenotype resembling the core symptoms of the patient. Patient IgG selectively bound to rat amygdala, hippocampus, and frontal cortical areas. In cultured rat hippocampal neurons, patient IgG inhibited GABA release. In line with these experimental results, the GABA-A receptor binding potential was reduced in the patient's amygdala/hippocampus complex. No motor abnormalities were found in recipient rats. Conclusion/Significance: The observations in rats after passive transfer lead us to propose that anxiety-like behavior can be induced in rats by passive transfer of IgG from a SPS patient positive for anti-GAD 65 antibodies. Anxiety, in this case, thus may be an antibody-mediated phenomenon with consecutive disturbance of GABAergic signaling in the amygdala region.},
  subject      = {Medizin},
  language  = {en}
}
@article{KleinschnitzGrundWingleretal.2010,
  author    = {Kleinschnitz, Christoph and Grund, Henrike and Wingler, Kirstin and Armitage, Melanie E. and Jones, Emma and Mittal, Manish and Barit, David and Schwarz, Tobias and Geis, Christian and Kraft, Peter and Barthel, Konstanze and Schuhmann, Michael K. and Herrmann, Alexander M. and Meuth, Sven G. and Stoll, Guido and Meurer, Sabine and Schrewe, Anja and Becker, Lore and Gailus-Durner, Valerie and Fuchs, Helmut and Klopstock, Thomas and de Angelis, Martin Hrabe and Jandeleit-Dahm, Karin and Shah, Ajay M. and Weissmann, Norbert and Schmidt, Harald H. H. W.},
  title     = {Post-Stroke Inhibition of Induced NADPH Oxidase Type 4 Prevents Oxidative Stress and Neurodegeneration},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68416},
  year      = {2010},
  abstract  = {Ischemic stroke is the second leading cause of death worldwide. Only one moderately effective therapy exists, albeit with contraindications that exclude 90\% of the patients. This medical need contrasts with a high failure rate of more than 1,000 pre-clinical drug candidates for stroke therapies. Thus, there is a need for translatable mechanisms of neuroprotection and more rigid thresholds of relevance in pre-clinical stroke models. One such candidate mechanism is oxidative stress. However, antioxidant approaches have failed in clinical trials, and the significant sources of oxidative stress in stroke are unknown. We here identify NADPH oxidase type 4 (NOX4) as a major source of oxidative stress and an effective therapeutic target in acute stroke. Upon ischemia, NOX4 was induced in human and mouse brain. Mice deficient in NOX4 (Nox42/2) of either sex, but not those deficient for NOX1 or NOX2, were largely protected from oxidative stress, blood-brain-barrier leakage, and neuronal apoptosis, after both transient and permanent cerebral ischemia. This effect was independent of age, as elderly mice were equally protected. Restoration of oxidative stress reversed the stroke-protective phenotype in Nox42/2 mice. Application of the only validated low-molecular-weight pharmacological NADPH oxidase inhibitor, VAS2870, several hours after ischemia was as protective as deleting NOX4. The extent of neuroprotection was exceptional, resulting in significantly improved long-term neurological functions and reduced mortality. NOX4 therefore represents a major source of oxidative stress and novel class of drug target for stroke therapy.},
  subject      = {Schlaganfall},
  language  = {en}
}
@phdthesis{Geis2004,
  author    = {Geis, Christian},
  title     = {Charakterisierung von Spinalganglienneuronen intakter und l{\"a}dierter Afferenzen},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-13926},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2004},
  abstract  = {Am Tiermodell einer experimentellen Mononeuropathie (chronic constriction injury, CCI) wurde bei Ratten die Expression von Zytokinen (TNF-\&\#945;, IL-10), Vanilloidrezeptor 1 (VR1) und Neuropeptiden in Spinalganglienneuronen immunhistochemisch analy-siert. Durch retrograde Anf{\"a}rbung mit den Tracern Fluorogold (FG) und Fluoruby (FR) konnten intakte von gesch{\"a}digten Neuronen unterschieden und Muskel- und Hautaffe-renzen getrennt untersucht werden. Nach CCI fand sich ein selektiver Anstieg der TNF-\&\#945; Immunreaktivit{\"a}t in mittelgroßen und großen Spinalganglienneuronen, welche durch Vergleich mit anderen neuronalen Markern als A-Faser Neurone identifiziert werden konnten. Nicht nur gesch{\"a}digte, sondern auch intakte Spinalganglienneurone wiesen eine erh{\"o}hte TNF-\&\#945; Immunreaktivit{\"a}t auf und sowohl Muskel- als auch Hautafferenzen trugen zur vermehrten TNF-\&\#945; Expression bei. IL-10, VR1 und IB4 Immunreaktivit{\"a}t fand sich vor allem in kleinen Neuronen und war nach CCI deutlich reduziert, w{\"a}hrend die Expression von CGRP in kleinen und mittel-großen Spinalganglienneuronen nachzuweisen war und keine Ver{\"a}nderung zeigte. Die Ergebnisse zeigen, dass intakt gebliebene A-Faser Neurone pathophysiologische Ver{\"a}nderungen im Sinne einer vermehrten Expression des pro-inflammatorischen Zyto-kins TNF-\&\#945; erfahren. Dieser ph{\"a}notypische Switch ist m{\"o}glicherweise mit einer neuen Funktion dieser Neurone im nozizeptiven System verbunden. Die verminderte Expression des anti-inflammatorischen Zytokins IL-10 vier Tage nach CCI korrespondiert mit der fr{\"u}hen Schmerzentstehung nach peripherer Nervenl{\"a}sion und der noch fehlenden Suppression der pro-inflammatorischen Zytokine zu diesem Zeitpunkt. Dagegen ist der R{\"u}ckgang der VR1 und IB4 Konzentrationen im Spinal-ganglion am ehesten durch einen l{\"a}sionsbedingten Mangel an neurotrophen Faktoren zu erkl{\"a}ren. Die in dieser Arbeit gewonnenen Erkenntnisse unterst{\"u}tzen die These, dass pro-inflammatorischen Zytokinen, insbesondere TNF-\&\#945;, eine besondere Bedeutung bei der Entstehung neuropathischer Schmerzen zukommt. Dies k{\"o}nnte ein Ansatzpunkt f{\"u}r wei-tere Studien sein, die Wirksamkeit TNF-\&\#945; hemmender Medikamente bei neuropathi-schen Schmerzmodellen im Tierversuch und eventuell sp{\"a}ter klinisch zu untersuchen.},
  language  = {de}
}