AMPA RECEPTOR ANTAGONIST, YM90K, REDUCES INFARCT VOLUME IN THROMBOTICDISTAL MIDDLE CEREBRAL-ARTERY OCCLUSION IN SPONTANEOUSLY HYPERTENSIVERATS

We examined the effects of a potent and selective antagonist of alpha- amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) subtype of glutamate receptor, YM90K, on brain infarction using a newly developed stroke model of thrombotic distal middle cerebral artery occlusion. M ale spontaneously hypertensive rats (5-7 months old) were subjected to photochemically-induced distal middle cerebral artery occlusion as pr eviously described [Stroke 26 (1996) 333-336]. Intravenous infusion of YM90K (n = 8) (5 mg/kg per h for 1 h) or the same amount of vehicle ( n = 8) (alkaline saline) was started 5 min after distal middle cerebra l artery occlusion. Penumbral cerebral blood flow was determined with laser-Doppler flowmetry. Three days after the ischemic insult, brains were stained with 2,3,5-triphenyltetrazolium cholride and infarct volu mes were determined. One hour infusion of YM90K significantly reduced infarct volume by 34% (93 +/- 23 mm(3) in control group vs. 61 +/- 25 mm(3) in YM90K-treated group, P = 0.017). There were no significant di fferences in the degrees of cerebral blood flow reduction after distal middle cerebral artery occlusion between the YM90K treated and contro l groups. YM90K reduces infarct volume in experimental ischemia produc ed by photothrombotic distal middle cerebral artery occlusion in rats. The present results demonstrated beneficial effects of AMPA receptor blockade on acute ischemic stroke.