{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:49:04Z","timestamp":1790142544189,"version":"4.0.1"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2003,4,25]],"date-time":"2003-04-25T00:00:00Z","timestamp":1051228800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2003,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Glutamate excitotoxicity is implicated in the progressive loss of oligodendrocytes in multiple sclerosis, but how glutamate metabolism is dysregulated in the disease remains unclear. Because there is microglia activation in all stages of multiple sclerosis, we determined whether a microglia product, interleukin\u20101\u03b2, could provide the mechanism for glutamate excitotoxicity. We found that whereas interleukin\u20101\u03b2 did not kill oligodendrocytes in pure culture, it produced apoptosis of oligodendrocytes in coculture with astrocytes and microglia. This requirement for a mixed glia environment suggests that interleukin\u20101\u03b2 impairs the well\u2010described glutamate\u2010buffering capacity of astrocytes. In support, antagonists at AMPA\/kainate glutamate receptors, NBQX and CNQX, blocked the interleukin\u20101\u03b2 toxicity to oligodendrocytes. Another microglia\/macrophage cytokine, tumor necrosis factor\u2010\u03b1, also evoked apoptosis of oligodendrocytes in a mixed glia environment in an NBQX\u2010blockable manner. These results provide a mechanistic link between the persistent and insidious microglia activation that is evident in all stages of multiple sclerosis, with the recent appreciation that glutamate excitotoxicity leads to the destruction of oligodendrocytes in the disease. 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