EFFECTS OF A NOVEL FREE-RADICAL SCAVENGER, MCI-186, ON ISCHEMIC BRAIN-DAMAGE IN THE RAT DISTAL MIDDLE CEREBRAL-ARTERY OCCLUSION MODEL

We investigated the effects of a free radical scavenger, 3-methyl-1-ph enyl-2-pyrazolin-5-one (MCI-186), on infarct areas, neurological defic its and regional cerebral blood flow (rCBF), with use of a rat thrombo tic distal middle cerebral artery (dMCA) occlusion model to elucidate its possible therapeutic effects on focal cerebral ischemia. In additi on, we have attempted to measure 2-oxo-3-(phenylhydrazono)-butanoic ac id (OPE), which is the major oxidation product of MCI-186, in the penu mbral cortex of a thrombotic dMCA occlusion model. Postischemic treatm ent with MCI-186 (3 mg/kg) significantly (P < .05) decreased the size of the cerebral infarcts 1 day after dMCA occlusion. MCI-186 (3 mg/kg) significantly (P < .05) improved the neurological deficits 1 day afte r dMCA occlusion. On the contrary, MCI-186 had no effect on rCBF 1 day after dMCA occlusion. MCI-186 mainly reacted into OPE by peroxidation in rat brain homogenates. Furthermore, the increase in OPE content in the ischemic penumbral cortex tissue was confirmed after 90 min of MC I-186 perfusion. These results suggest that MCI-186 has a protective e ffect on brain ischemia by reacting with oxygen radicals and that oxyg en radicals are closely related to postischemic brain injury.