NMDA antagonists: lack of protective effect against hypoxic damage in CA1 region of hippocampal slices

Abstract

Rat hippocampal slices were exposed to a hypoxic insult in control medium or while exposed to the N-methyl-D-aspartate (NMDA) receptor antagonists DL-2-amino-7-phosphonoheptanoic acid (100 microM) or DL-2-amino-5-phosphonovaleric acid (25 or 100 microM). Synaptic transmission between Schaffer collaterals and CA 1 pyramidal cells was evaluated before and after the hypoxic period, and the DC potential in the CA 1 pyramidal cell layer was monitored during the hypoxic period. Neither antagonist significantly increased the proportion of slices in which synaptic transmission recovered following hypoxia, nor did they increase the latency of the spreading depression-like anoxic depolarization. We suggest that NMDA receptors are not involved in neural damage caused by severe hypoxia with sudden onset, while they may play a role in the effects of more moderate, gradual onset hypoxia and in post-ischemic reperfusion effects.