NMDA AND NON-NMDA RECEPTOR GENE-EXPRESSION FOLLOWING GLOBAL BRAIN ISCHEMIA IN RATS - EFFECT OF NMDA AND NON-NMDA RECEPTOR ANTAGONISTS

Transient forebrain or global ischemia in rats induces selective and d elayed damage of hippocampal CA1 neurons. In a previous study, we have shown that expression of GluR2, the lpha-amino-3-hydroxy-5-methyl-4-i soxazolepropionic acid (AMPA) receptor subunit that governs Ca2+ perme ability, is preferentially reduced in CA1 at a time point preceding ne uronal degeneration. Postischemic administration of the selective AMPA receptor antagonist, 3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxali ne (NBQX), protects CA1 neurons against delayed death. In this study w e examined the effects of NBQX (at a neuroprotective dose) and of MK-8 01 (a selective NMDA receptor antagonist, not protective in this model ) on kainate/AMPA receptor gene expression changes after global ischem ia. We also examined the effects of transient forebrain ischemia on ex pression of the NMDA receptor subunit NMDAR1. In ischemic rats treated with saline, GluR2 and GluR3 mRNAs were markedly reduced in CA1 but w ere unchanged in CA3 or dentate gyrus. GluR1 and NMDAR1 mRNAs were not significantly changed in any region examined. Administration of NBQX or MK-801 did not alter the ischemia-induced changes in kainate/AMPA r eceptor gene expression. These findings suggest that NBQX affords neur oprotection by a direct blockade of kainate/AMPA receptors, rather tha n by a modification of GluR2 expression changes.