AMPA receptor antagonist, YM90K, reduces infarct volume in thrombotic distal middle cerebral artery occlusion in spontaneously hypertensive rats

Abstract

We examined the effects of a potent and selective antagonist of α-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. Male spontaneously hypertensive rats (5–7 months old) were subjected to photochemically-induced distal middle cerebral artery occlusion as previously 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 cerebral 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 volumes 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 differences in the degrees of cerebral blood flow reduction after distal middle cerebral artery occlusion between the YM90K treated and control groups. YM90K reduces infarct volume in experimental ischemia produced by photothrombotic distal middle cerebral artery occlusion in rats. The present results demonstrated beneficial effects of AMPA receptor blockade on acute ischemic stroke.