A novel Na+ and Ca2+ channel blocker, T-477, prevents brain edema following microsphere-induced permanent occlusion of cerebral arterioles in rats

One of the most common acute complications of stroke is brain edema. Treatm ent of edema is recommended when the condition of the patients is deteriora ting. The present study was undertaken to evaluate the effect of T-477 [(R) -(+)-2-(4-chlorophenyl)-2,3-dihydro-4-diethyl aminoacetyl-4H-1,4-benzo-thia zine hydrochloride], a novel neuronal Na+ and Ca2+ channel blocker, on brai n edema in rats. Cerebral ischemia was induced by intra-arterial infusion o f 1000 microspheres into the forebrain of freely moving rats, resulting in brain edema. T-477 was intravenously infused continuously for 24 h or twice for 3 h with a 3-h interval between infusions immediately after microspher e injection. T-477 dose-dependently inhibited the increase in brain water c ontent by both infusion procedures; the inhibition was statistically signif icant at doses of 25 mg/kg per 24 h and 14 mg/kg per 9 h. Additionally, inf usion of T-477 at a dose of 14 mg/kg per 9 h significantly inhibited the de crease in K content and the increase in Ca content of the forebrain. In con clusion, T-477 prevents brain edema following microsphere-induced cerebral embolism in rats.