1. Aquaporin-4 autoantibodies increase vasogenic edema formation and infarct size in a rat stroke model.
- Author
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Juenemann M, Braun T, Doenges S, Nedelmann M, Mueller C, Bachmann G, Singh P, Blaes F, Gerriets T, and Tschernatsch M
- Subjects
- Animals, Brain Edema etiology, Brain Edema immunology, Cerebral Cortex pathology, Cerebral Infarction complications, Cerebral Infarction immunology, Disease Models, Animal, Male, Neuromyelitis Optica immunology, Rats, Rats, Wistar, Stroke, Aquaporin 4 immunology, Autoantibodies administration & dosage, Brain Edema prevention & control, Cerebral Cortex drug effects, Cerebral Infarction therapy
- 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.
- Published
- 2015
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