Glutamate excitotoxicity in a model of multiple sclerosis.
Nat Med
; 6(1): 67-70, 2000 Jan.
Article
en En
| MEDLINE
| ID: mdl-10613826
ABSTRACT
Glutamate excitotoxicity mediated by the AMPA/kainate type of glutamate receptors damages not only neurons but also the myelin-producing cell of the central nervous system, the oligodendrocyte. In multiple sclerosis, myelin, oligodendrocytes and some axons are lost as a result of an inflammatory attack on the central nervous system. Because glutamate is released in large quantities by activated immune cells, we expected that during inflammation in MS, glutamate excitotoxicity might contribute to the lesion. We addressed this by using the AMPA/kainate antagonist NBQX to treat mice sensitized for experimental autoimmune encephalomyelitis, a demyelinating model that mimics many of the clinical and pathologic features of multiple sclerosis. Treatment resulted in substantial amelioration of disease, increased oligodendrocyte survival and reduced dephosphorylation of neurofilament H, an indicator of axonal damage. Despite the clinical differences, treatment with NBQX had no effect on lesion size and did not reduce the degree of central nervous system inflammation. In addition, NBQX did not alter the proliferative activity of antigen-primed T cells in vitro, further indicating a lack of effect on the immune system. Thus, glutamate excitotoxicity seems to be an important mechanism in autoimmune demyelination, and its prevention with AMPA/kainate antagonists may prove to be an effective therapy for multiple sclerosis.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Quinoxalinas
/
Ácido Glutámico
/
Antagonistas de Aminoácidos Excitadores
/
Encefalomielitis Autoinmune Experimental
/
Esclerosis Múltiple
Límite:
Animals
Idioma:
En
Revista:
Nat Med
Asunto de la revista:
BIOLOGIA MOLECULAR
/
MEDICINA
Año:
2000
Tipo del documento:
Article
País de afiliación:
Estados Unidos