Protection against ischemic hippocampal CAI damage in the rat with a new non-NMDA antagonist, NBQX

Abstract
Two glutamate antagonists were tested in a rat model of complete, transient cerebral ischemia. Six days after 10 min ischemia the mean loss of hippocampal CAI pyramidal neurones was 73%. Administration of the AMPA (a-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid) antagonist NBQX (2,3-dihydro-6-nitro-7-sulfamoyl-benzo(F)quinoxaline) reduced the pyramidal neurone loss to 1%, 11% and 15%, when given before, immediately after or 1 h after ischemia, respectively. MK-801 (dizocilpine), a competitive NMDA antagonist gave no protection in this model. We suggest that the AMPA receptor transduction mechanisms are sensitized by ischemia and that the postischemic blockade of the main glutamatergic input to the CA 1 cells with NBQX impairs the deleterious effect of “normal” postischemic excitatory transmission.