ETHANOL, STROKE, BRAIN-DAMAGE, AND EXCITOTOXICITY

The N-methyl-d-aspartate (NMDA)-glutamate receptor could contribute to stroke, trauma, and alcohol-induced brain damage through activation o f nitric oxide formation and excitotoxicity. In rat primary cortical c ultures NMDA was more potent at activating nitric oxide formation than triggering excitotoxicity. Ethanol dose dependently inhibited both re sponses. In contrast, treatment of neuronal cultures with ethanol (100 mM) for 4 days significantly increased NMDA stimulated nitric oxide f ormation and excitotoxicity. These findings suggest that ethanol acute ly inhibits but chronically causes supersensitivity to NMDA-induced ex citotoxicity in neuronal cultures. To investigate ethanol's interactio n with stroke induced damage models of global cerebral ischemia were s tudied. Transient global ischemia resulted in a loss of hippocampal CA 1 pyramidal neurons over a 3- to 5-day period. Determinations of the N MDA receptor ligand binding stoichiometry or postischemic receptor bin ding changes did not show differences between neurons that undergo del ayed neuronal death following ischemia and those that show no toxicity , for example, CA1 and dentate gyrus, respectively. Acute ethanol (3 g /kg) was found to protect against ischemia-induced CA1 hippocampal dam age by lowering body temperature, but not under temperature controled conditions. These studies indicate that the factors contributing to st roke-induced brain damage are complex, although they are consistent wi th chronic ethanol increasing stroke-induced brain damage by increasin g NMDA excitotoxicity. (C) 1998 Elsevier Science Inc.