SHORT THERAPEUTIC WINDOW FOR MK-801 IN TRANSIENT FOCAL CEREBRAL-ISCHEMIA IN NORMOTENSIVE RATS

The present study investigates the role of N-methyl-D-aspartate (NMDA) receptors in a model of transient focal cerebral ischemia in normoten sive rats. The left middle cerebral artery and both common carotid art eries were occluded for 60 min. Preliminary studies indicated that thi s gave reproducible infarctions of the cortex and striatum. These infa rctions were the result of severe ischemia followed by complete reperf usion after clamp removal, as showed by striatal tissue Po-2 monitorin g. Microdialysis indicated that glutamate concentration increased imme diately after occlusion and returned to the baseline value 40 min afte r clamp removal. MK-801 (1 mg kg(-1) i.v.), an antagonist of the NMDA glutamatergic receptor, reduced the cortical infarct volume by 29% (p < 0.001) and the striatal infarct volume by 14% (p < 0.05) when given just prior to ischemia, but had no neuroprotective activity when given 30 min after the onset of ischemia. This short therapeutic window for MK-801 suggests that NMDA receptors play only a transient role in rev ersible focal ischemia in rats.