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 reactive events that follow cerebral ischemic damage. Antagonists of the N-methyl-D-aspartate (NMDA) subclass of glutamate receptors are thought to ameliorate functional outcome after ischemic injury. To assess whether glutamate NMDA receptor blockade could alter GAP-43 postischemic induction we performed immunocytochemistry in rat brains that had been subjected to middle cerebral artery occlusion. Cortical cells did not constitutively express GAP-43, yet focal ischemia induced its expression, with an intense signal generated in cells over the lesioned area at 6 h, increasing at 24 h postischemia. This signal was effectively decreased by pretreatment with the NMDA receptor antagonist (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-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 NMDA receptor during ischemia is linked to GAP-43 expression.
Luque
J M
JM
Instituto de Neurociencias, Universidad Miguel Hernández, San Juan, Alicante, Spain.
Puig
N
N
Martínez
J M
JM
González-García
C
C
Ceña
V
V
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D019922:GAP-43 Protein / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics*; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000235:genetics* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D019782:Riluzole / Q000494:pharmacology; D013997:Time Factors; D015533:Transcriptional Activation
D018691:Excitatory Amino Acid Antagonists; D019922:GAP-43 Protein; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D019782:Riluzole