TRIGGERING AND EXECUTION OF NEURONAL DEATH IN BRAIN ISCHEMIA - 2 PHASES OF GLUTAMATE RELEASE BY DIFFERENT MECHANISMS

A reduced blood or oxygen supply to the brain leads to neuronal death caused by excessive activation of glutamate receptors. Recent evidence suggests that two distinct phases of glutamate release produce this d eath. During ischaemia or hypoxia, glutamate is released by reversed o peration of glutamate uptake carriers. it activates N-methyi-D-asparta te (NMDA) receptors, increases the intracellular concentration of Ca2, and triggers a long-lasting potentiation of NIMDA-receptor-gated cur rents. After ischaemia, glutamate released by Ca2+-dependent exocytosi s activates an excessive influx of Ca2+ largely through potentiated NM DA-receptor-channels which leads to neuronal death. The therapeutic im plications of such a scheme are discussed.