Effects of a novel free radical scavenger, MCl-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-phenyl-2-pyrazolin-5-one (MCl-186), on infarct areas, neurological deficits and regional cerebral blood flow (rCBF), with use of a rat thrombotic distal middle cerebral artery (dMCA) occlusion model to elucidate its possible therapeutic effects on focal cerebral ischemia. In addition, we have attempted to measure 2-oxo-3-(phenylhydrazono)-butanoic acid (OPB), which is the major oxidation product of MCl-186, in the penumbral cortex of a thrombotic dMCA occlusion model. Postischemic treatment with MCl-186 (3 mg/kg) significantly (P < .05) decreased the size of the cerebral infarcts 1 day after dMCA occlusion. MCl-186 (3 mg/kg) significantly (P < .05) improved the neurological deficits 1 day after dMCA occlusion. On the contrary, MCl-186 had no effect on rCBF 1 day after dMCA occlusion. MCl-186 mainly reacted into OPB by peroxidation in rat brain homogenates. Furthermore, the increase in OPB content in the ischemic penumbral cortex tissue was confirmed after 90 min of MCl-186 perfusion. These results suggest that MCI-186 has a protective effect on brain ischemia by reacting with oxygen radicals and that oxygen radicals are closely related to postischemic brain injury.