title: Aquaporin-4 autoantibodies increase vasogenic edema formation and infarct size in a rat stroke model.
abstract: BACKGROUND
  Neuromyelitis optica (NMO) is an autoimmune disorder of the central nervous system, which is characterized by autoantibodies directed against the water channel aquaporin-4 (AQP4). As one of the main water regulators in the central nervous system, APQ4 is supposed to be involved in the dynamics of brain edema. Cerebral edema seriously affects clinical outcome after ischemic stroke; we therefore aimed to investigate whether NMO-antibodies may exert the same functional effects as an AQP4-inhibitor in-vivo in acute ischemic stroke.
  
  
  METHODS
  Sixteen male Wistar rats were randomized into two groups twice receiving either purified NMO-IgG or immune globulin from healthy controls, 24 hours and 30 minutes before middle cerebral artery occlusion (MCAO) was performed. T2-weighted MRI was carried out 24 hours after MCAO.
  
  
  RESULTS
  MRI-examination showed a significant increase of infarct size in relation to the cerebral hemisphere volume with NMO-IgG treated animals (27.1% ± 11.1% vs. 14.3% ± 7.2%; p < 0.05) when corrected for the space-occupying effect of vasogenic edema formation and similar results without edema correction (34.4% ± 16.4% vs. 17.5% ± 9.3%; p < 0.05). Furthermore, T2-RT revealed a significant increase in cortical brain water content of the treatment group (19.5 ms ± 9.7 ms vs. 9.2 ms ± 5.2 ms; p < 0.05).
  
  
  CONCLUSIONS
  These results support the functional impact of NMO-antibodies and also offer an in-vivo-applicable animal model to investigate the properties of AQP4 in ischemic stroke.
authors.affiliation: Heart & Brain Research Group, Justus-Liebig-University Giessen and Kerckhoff Clinic, Benekestrasse 2-8, 61231, Bad Nauheim, Germany. martin.juenemann@neuro.med.uni-giessen.de.|Department of Neurology, Justus-Liebig-University Giessen, Klinikstrasse 33, 35392, Giessen, Germany. martin.juenemann@neuro.med.uni-giessen.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Juenemann
authors.affiliation: Department of Neurology, Justus-Liebig-University Giessen, Klinikstrasse 33, 35392, Giessen, Germany. tobias.braun@neuro.med.uni-giessen.de.
authors.forename: Tobias
authors.initials: T
authors.lastname: Braun
authors.affiliation: Heart & Brain Research Group, Justus-Liebig-University Giessen and Kerckhoff Clinic, Benekestrasse 2-8, 61231, Bad Nauheim, Germany. s.marhoffer@gmx.de.
authors.forename: Simone
authors.initials: S
authors.lastname: Doenges
authors.affiliation: Heart & Brain Research Group, Justus-Liebig-University Giessen and Kerckhoff Clinic, Benekestrasse 2-8, 61231, Bad Nauheim, Germany. max.nedelmann@neuro.med.uni-giessen.de.|Department of Neurology, Justus-Liebig-University Giessen, Klinikstrasse 33, 35392, Giessen, Germany. max.nedelmann@neuro.med.uni-giessen.de.
authors.forename: Max
authors.initials: M
authors.lastname: Nedelmann
authors.affiliation: Department of Radiology, Kerckhoff Clinic, Benekestrasse 2-8, 61231, Bad Nauheim, Germany. c.mueller@kerckhoff-klinik.de.
authors.forename: Clemens
authors.initials: C
authors.lastname: Mueller
authors.affiliation: Department of Radiology, Kerckhoff Clinic, Benekestrasse 2-8, 61231, Bad Nauheim, Germany. g.bachmann@kerckhoff-klinik.de.
authors.forename: Georg
authors.initials: G
authors.lastname: Bachmann
authors.affiliation: Department of Pharmacology, Max-Planck-Institute for Heart and Lung Research, Ludwigstraße 43, 61231, Bad Nauheim, Germany. pratibha.singh@mpi-bn.mpg.de.
authors.forename: Pratibha
authors.initials: P
authors.lastname: Singh
authors.affiliation: Department of Neurology, Justus-Liebig-University Giessen, Klinikstrasse 33, 35392, Giessen, Germany. franz.blaes@kkh-gummersbach.de.|Department of Neurology, Kreiskrankenhaus Gummersbach, Wilhelm-Breckow-Allee 20, 51643, Gummersbach, Germany. franz.blaes@kkh-gummersbach.de.
authors.forename: Franz
authors.initials: F
authors.lastname: Blaes
authors.affiliation: Heart & Brain Research Group, Justus-Liebig-University Giessen and Kerckhoff Clinic, Benekestrasse 2-8, 61231, Bad Nauheim, Germany. tibo.gerriets@neuro.med.uni-giessen.de.|Department of Neurology, Justus-Liebig-University Giessen, Klinikstrasse 33, 35392, Giessen, Germany. tibo.gerriets@neuro.med.uni-giessen.de.|Department of Neurology, Buergerhospital Friedberg, Ockstaedter Strasse 3-5, 61169, Friedberg, Germany. tibo.gerriets@neuro.med.uni-giessen.de.
authors.forename: Tibo
authors.initials: T
authors.lastname: Gerriets
authors.affiliation: Department of Neurology, Justus-Liebig-University Giessen, Klinikstrasse 33, 35392, Giessen, Germany. marlene.tschernatsch@neuro.med.uni-giessen.de.
authors.forename: Marlene
authors.initials: M
authors.lastname: Tschernatsch
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000276:immunology*; D001323:Autoantibodies / Q000008:administration & dosage*; D001929:Brain Edema / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology; D002544:Cerebral Infarction / Q000150:complications / Q000276:immunology / Q000628:therapy*; D004195:Disease Models, Animal; D008297:Male; D009471:Neuromyelitis Optica / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke
chemical_list: D051401:Aquaporin 4; D001323:Autoantibodies