Abstract
We investigated the effects of a free radical scavenger, 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-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 MCI-186, in the penumbral cortex of a thrombotic dMCA occlusion model. Postischemic treatment 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 after dMCA occlusion. On the contrary, MCI-186 had no effect on rCBF 1 day after dMCA occlusion. MCI-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 MCI-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.
Footnotes
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Send reprint requests to: Hiroshi Kawai, Ph.D., Pharmaceuticals Laboratory 2, Yokohama Research Center, Mitsubishi Chemical Corporation, 1000, Kamoshida-cho, Aoba-ku Yokohama 227, Japan.
- Abbreviations:
- dMCA
- distal middle cerebral artery
- rCBF
- regional cerebral blood flow
- CCA
- common carotid artery
- IAP
- iodoantipyrine
- MCI-186
- 3-methyl-1-phenyl-2-pyrazolin-5-one
- OPB
- 2-oxo-3-(phenylhydrazono)-butanoic acid
- TBA
- tetrabutylammonium chloride
- HPLC
- high-performance liquid chromatography
- TTC
- 1% 2,3,5-triphenyltetrazolium chloride
- Received September 4, 1996.
- Accepted December 23, 1996.
- The American Society for Pharmacology and Experimental Therapeutics
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