SUBLETHAL OXYGEN-GLUCOSE DEPRIVATION ALTERS HIPPOCAMPAL NEURONAL AMPARECEPTOR EXPRESSION AND VULNERABILITY TO KAINATE-INDUCED DEATH

Recent studies have suggested that rats subjected to transient global brain ischemia develop depressed expression of GluR-B in CA1 hippocamp al neurons. The present study was performed to determine whether a sim ilar change in AMPA receptor expression could be triggered in vitro by sublethal oxygen-glucose deprivation in rat hippocampal neuronal cult ures. mRNA was extracted from individual hippocampal neurons via patch electrodes and amplified by RT-PCR 24-48 hr after sublethal oxygen-gl ucose deprivation. Compared with controls, insulted neurons expressed increased levels of GluR-D flop. As an indication that this change in receptor expression was functionally significant, insulted cultures ex hibited increased AMPA- or kainate-induced Ca-45(2+) accumulation sens itive to Joro spider toxin and increased vulnerability to kainate-indu ced death. These data support the hypothesis that exposure to ischemia may enhance subsequent hippocampal neuronal vulnerability to AMPA rec eptor-mediated excitotoxicity by modifying the relative expression of AMPA receptor subunits in a manner that promotes Ca2+ permeability.