Glutamate N-methyl-D-aspartate receptor blockade prevents induction of GAP-43 after focal ischemia in rats

Growth associated protein-43 (GAP-43) gene induction may be involved in rea ctive events that follow cerebral ischemic damage. Antagonists of the N-met hyl-D-aspartate (NMDA) subclass of glutamate receptors are thought to ameli orate functional outcome after ischemic injury. To assess whether glutamate NMDA receptor blockade could alter GAP-43 postischemic induction we perfor med immunocytochemistry in rat brains that had been subjected to middle cer ebral artery occlusion. Cortical cells did not constitutively express GAP-4 3, yet focal ischemia induced its expression, with an intense signal genera ted in cells over the lesioned area at 6 h, increasing at 24 h postischemia . This signal was effectively decreased by pretreatment with the NM DA rece ptor antagonist (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohe pten-5,10-imine hydrogen maleate (0.1 mg/kg s.c.), but not by the glutamate release blocker riluzole (8 mg/kg i.v.), suggesting that overactivation of NM DA receptor during ischemia is linked to GAP-43 expression. (C) 2001 El sevier Science Ireland Ltd. All rights reserved.