GLUTAMATE ANTAGONIST MK-801 ATTENUATES INCOMPLETE BUT NOT COMPLETE INFARCTION IN THROMBOTIC DISTAL MIDDLE CEREBRAL-ARTERY OCCLUSION IN WISTAR RATS

The purpose of this study was to investigate the effects of a non-comp etitive N-methyl-D-aspartate antagonist, MK-801, on incomplete infarct ion (selective neuronal necrosis), a zone of which had been found prev iously in a thrombotic distal middle cerebral artery (MCA) occlusion m odel in Wistar rats. Male Wistar rats were treated with 1 mg/kg of MK- 801 or saline 30 min before MCA occlusion. Laser irradiation with intr avenous administration of Rose Bengal dye was used to cause thrombotic distal MCA occlusion. The ipsilateral common carotid artery was occlu ded permanently and the contralateral carotid artery for 60 min. Head temperature was controlled at 36 degrees C. Cerebral blood flow (CBF) was determined with laser-Doppler flowmetry. Three days after the isch emic insult, brains were perfusion-fixed and volumes of cortical (comp lete and incomplete) infarction were determined. There were no signifi cant differences in physiological variables or CBF between the two gro ups. Volumes of complete infarction were equivalent between the two gr oups (94.9 +/- 15.6 mm(3) and 91.6 +/- 14.0 mm(3) in the control and M K-801 treated groups, respectively). In MK-801 treated group, the volu me of incomplete infarction was reduced by 44% (6.4 +/- 1.7 mm(3) vs. 3.6 +/- 2.1 mm(3) in control and MK-801 treated groups, respectively, P < 0.05). Although the zone responsive to MK-801 was small in this th rombotic MCA occlusion model, our present study revealed that MK-801 h as a beneficial effect on the tissue zone containing selective neurona l alterations (incomplete infarction). Our results support the concept that this drug is effective in the area of less severe ischemia.