NMDA RECEPTOR INHIBITION USING ANTISENSE OLIGONUCLEOTIDES PREVENTS DELAYED NEURONAL DEATH IN GERBIL HIPPOCAMPUS FOLLOWING CEREBRAL-ISCHEMIA

Glutamate plays a key role in central nervous system by modulating syn aptic plasticity of the neurons as well as neuronal cell death. These processes are mediated through the activation of N-methyl-D-aspartate (NMDA) receptors and the resulting influx of Ca2+. We examined the eff ects of inhibition of the NMDA receptors at the molecular level on isc hemic neuronal injury in the CA(1) region of the hippocampus. In the g erbil hippocampus, antisense oligonucleotides (ODNs) directed against the NMDA receptor (NMDAR1) reduced the level of NMDA receptor mRNA and ligand binding in the CA(1) region. Sense or nonsense oligonucleotide s had no effect upon the NMDA receptor. Administration of antisense NM DAR1 ODNs prevented delayed neuronal death (DND) following 5 min of ce rebral ischemia, whereas, sense ODNs did not alter the effects of isch emia. These results suggest that the NMDA receptor is involved in the process of DND during cerebral ischemia.