BLOCKADE OF GLUTAMATE RECEPTORS UNMASKS NEURONAL APOPTOSIS AFTER OXYGEN-GLUCOSE DEPRIVATION IN-VITRO

Mouse cortical cell cultures exposed to transient oxygen-glucose depri vation developed marked acute cell body swelling followed by neurodege neration, consistent with necrosis-type death. This death was not atte nuated by the protein synthesis inhibitor, cycloheximide, but was atte nuated by addition of the N-methyl-D-asparate antagonist, MK-801 (dizo cilpine maleate), and the lpha-amino-3-hydroxy-5-methyl-4-isoxazolepro pionic acid/kainate antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione. If the deprivation insult was extended to overcome the protective effe ct of glutamate antagonists, neuronal death resulted that was associat ed with cell body shrinkage and DNA fragmentation, and was attenuated by cycloheximide. These data suggest that oxygen-glucose deprivation c an induce in cortical neurons both excitotoxic necrosis, and apoptosis dependent on new macromolecule synthesis.