Memantine abrogates neurological deficits, but not CNS inflammation, in Lewis rat experimental autoimmune encephalomyelitis
Autor: | Carl-Gustaf Nilsson, Åke Ljungdahl, Mohsen Khademi, Per Diener, Tomas Olsson, Erik Wallström |
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Rok vydání: | 1996 |
Předmět: |
Male
Encephalomyelitis Autoimmune Experimental Encephalomyelitis T-Lymphocytes Lymphocyte proliferation Receptors N-Methyl-D-Aspartate Interferon-gamma Central Nervous System Diseases Memantine medicine Animals Interferon gamma RNA Messenger Neuroinflammation Autoimmune disease biology Dose-Response Relationship Drug business.industry Experimental autoimmune encephalomyelitis Myelin Basic Protein medicine.disease Immunohistochemistry Myelin basic protein Rats Neurology Spinal Cord Rats Inbred Lew Immunology biology.protein Neurology (clinical) business Excitatory Amino Acid Antagonists Cell Division medicine.drug |
Zdroj: | Karolinska Institutet |
ISSN: | 0022-510X |
Popis: | Memantine, a clinically employed drug with N-methyl-D-aspartate (NMDA) receptor antagonistic effects, dose-dependently ameliorates neurological deficits in Lewis rat experimental autoimmune encephalomyelitis (EAE). Interestingly, this therapeutic effect was not due to dampened CNS inflammation, as assessed by immunohistochemical evaluation of spinal cord tissue. Furthermore, numbers of interferon gamma (IFN gamma) mRNA expressing cells were not decreased, as assessed by in situ hybridization. Systemic immunity in terms of numbers of IFN gamma secreting cells in response to immunodominant myelin basic protein (MBP) peptides ex vivo was not reduced, and non-toxic doses of memantine did not affect lymphocyte proliferation or IFN gamma secretion in vitro. Considering these findings, we hypothesize that effector mechanisms responsible for reversible neurological deficits in EAE may involve NMDA receptors, and this highlights neurons as targets during autoimmune neuroinflammation. |
Databáze: | OpenAIRE |
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