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The Neuroprotective Agent SR 57746A Abrogates Experimental Autoimmune Encephalomyelitis and Impairs Associated Blood-Brain Barrier Disruption: Implications for Multiple Sclerosis Treatment

Experimental autoimmune encephalomyelitis (EAE) is a T cell autoimmune disorder that is a widely used animal model for multiple sclerosis (MS) and, as in MS, clinical signs of EAE are associated with blood-brain barrier (BBB) disruption. SR 57746A, a nonpeptide drug without classical immunosuppressi...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1999-10, Vol.96 (22), p.12855-12859
Main Authors: Bourrié, Bernard, Bribes, Estelle, Esclangon, Martine, Garcia, Laurent, Marchand, Jean, Thomas, Corinne, Maffrand, Jean-Pierre, Casellas, Pierre
Format: Article
Language:English
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Summary:Experimental autoimmune encephalomyelitis (EAE) is a T cell autoimmune disorder that is a widely used animal model for multiple sclerosis (MS) and, as in MS, clinical signs of EAE are associated with blood-brain barrier (BBB) disruption. SR 57746A, a nonpeptide drug without classical immunosuppressive properties, efficiently protected the BBB and impaired intrathecal IgG synthesis (two conventional markers of MS exacerbation) and consequently suppressed EAE clinical signs. This compound inhibited EAE-induced spinal cord mononuclear cell invasion and normalized tumor necrosis factor α and IFN-γ mRNA expression within the spinal cord. These data suggested that pharmacological intervention aimed at inhibiting proinflammatory cytokine expression within the central nervous system provided protection against BBB disruption, the first clinical sign of EAE and probably the key point of acute MS attacks. This finding could lead to the development of a new class of compounds for oral therapy of MS, as a supplement to immunosuppressive agents.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.96.22.12855