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. Treatment of edema is recommended when the condition of the patients is deteriorating. The present study was undertaken to evaluate the effect of T-477 [(R)-(+)-2-(4-chlorophenyl)-2,3-dihydro-4-aminoacetyl-4H-1,4-benzo-thiazine hydrochloride], a novel neuronal Na⁺ and Ca²⁺ channel blocker, on brain edema in rats. Cerebral ischemia was induced by intra-arterial infusion of 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 microsphere injection. T-477 dose-dependently inhibited the increase in brain water content by both infusion procedures; the inhibition was statistically significant at doses of 25 mg/kg per 24 h and 14 mg/kg per 9 h. Additionally, infusion of T-477 at a dose of 14 mg/kg per 9 h significantly inhibited the decrease in K content and the increase in Ca content of the forebrain. In conclusion, T-477 prevents brain edema following microsphere-induced cerebral embolism in rats.