ELIPRODIL, A NONCOMPETITIVE, NR2B-SELECTIVE NMDA ANTAGONIST, PROTECTSPYRAMIDAL NEURONS IN HIPPOCAMPAL SLICES FROM HYPOXIC ISCHEMIC DAMAGE/

The N-methyl-D-aspartate (NMDA) subtype of glutamate receptor is one p athway through which excessive influx of calcium has been suggested to trigger ischemia-induced delayed neuronal death. NMDA receptors are h eterooligomeric complexes comprised of both NR1 and NR2A-D subunits, i n various combinations. NR2B-containing NMDA complexes exhibit larger, more prolonged conductances than those lacking this subunit. We teste d the ability of the non-competitive, NR2B-selective NMDA antagonist e liprodil to (a) protect synaptic transmission in in vitro hippocampal slices from hypoxia, and (b) reduce ischemic delayed neuronal death in hippocampal organotypic slice cultures. Eliprodil markedly improved t he recovery of Schaffer collateral-CA1 excitatory postsynaptic potenti als following a 15 min hypoxic insult, with an EC50 of approximately 0 .5 mu M. Tn contrast to this functional protection, eliprodil did not reduce delayed death of CA1 pyramidal neurons in organotypic hippocamp al slice cultures treated with severe hypoxia plus hypoglycemia, thoug h it did potently protect CA3 pyramidal neurons in the same cultures. These data indicate that NMDA receptors containing NR2B subunits may p lay a role in long-term recovery of hippocampal synaptic function foll owing ischemia/hypoxia. Furthermore, the selective protection of CA3, but not CA1, pyramidal neurons suggests that NR2B-containing NMDA rece ptors may preferentially contribute to an excitotoxic component of isc hemia-induced delayed neuronal death. (C) 1998 Elsevier Science B.V.