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TY - JOUR AU - Pitt, David AU - Werner, Peter AU - Raine, Cedric S. PY - 2000 DA - 2000/01/01 TI - Glutamate excitotoxicity in a model of multiple sclerosis JO - Nature Medicine SP - 67 EP - 70 VL - 6 IS - 1 AB - 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 oligodendrocyte1. In multiple sclerosis, myelin, oligodendrocytes and some axons are lost as a result of an inflammatory attack on the central nervous system2. Because glutamate is released in large quantities by activated immune cells3, 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 damage4. 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. SN - 1546-170X UR - https://doi.org/10.1038/71555 DO - 10.1038/71555 ID - Pitt2000 ER -