Cerebroprotective action of a Na+/Ca2+ channel blocker NS-7 - I. Effect onthe cerebral infarction and edema at the acute stage of permanent middle cerebral artery occlusion in rats

The effect of a novel Na+/Ca2+ channel blocker NS-7 [4-(4-fluorophenyl)-2-m ethyl-6-(5-piperidinopentyloxy)pyrimidine hydrochloride] on the cerebral in farction. edema and brain energy metabolism was investigated in rats after permanent middle cerebral artery occlusion (MCAO). The infarction and brain water content were evaluated at 48 h and 24 h after MCAO, respectively. A single bolus injection of NS-7 (0.03125-0.25 mg/kg) immediately after MCAO produced a dose-dependent reduction in the infarct volume as well as edema both in the cerebral cortex and striatum. Glycerol (4 g/kg) also decreased water content both in the occluded and non-occluded brain, but it did not r educe the size of cerebral infarction. Unlike glycerol, NS-7 did not change the water content in non-occluded brain. Moreover. a significant protectiv e action was still observed even when NS-7 was injected once at 12 h after occlusion. In addition, NS-7 significantly reversed the decrease in tissue ATP content observed at 3 h but not at 0.5 h after MCAO. These findings sug gest that a Na+/Ca2+ channel blocker NS-7 protects cerebral tissues against ischemic insults by improving the disturbance of cerebral energy metabolis m and suppressing the cerebral edema. (C) 2001 Elsevier Science B.V. All ri ghts reserved.