PROTECTIVE EFFECT OF ZONISAMIDE, AN ANTIEPILEPTIC DRUG, AGAINST TRANSIENT FOCAL CEREBRAL-ISCHEMIA WITH MIDDLE CEREBRAL-ARTERY OCCLUSION-REPERFUSION IN RATS

Purpose: The antiepileptic effects of zonisamide (ZNS) have been well documented experimentally and clinically. The purpose of this study wa s to examine whether ZNS reduces cerebral damage after transient focal ischemia in rats. Methods: Ischemia was induced by a transient occlus ion of the left middle cerebral artery (MCA) with a 3-0 nylon monofila ment for 90 min. Neurological evaluation was performed by measuring th e event of neurological deficit of the contralateral forepaw and hindp aw at 10 min and 1 day after MCA occlusion (MCAo). Brain infarct size was determined by measuring triphenyltetrazonium chloride-negative sta ined area of the serial brain sections 1 day after MCAo. Results: The pre-or postischemic treatment with ZNS [(10-100 mg/kg p.o.), 30 min be fore and 4 h after or 15 min and 4 h after the occlusion] markedly red uced cerebral damage in the ipsilateral hemisphere and the neurologica l deficit induced by transient ischemia. The reducing effect on the da mage was observed in the cortical and subcortical regions. Preischemic treatment with carbamazepine (CBZ 60 mg/kg p.o. twice 30 min before a nd 4 h after MCAo) tended to reduce the cerebral damage and neurologic al deficit, but the lower dose (20 mg/kg p.o. twice) did not. Valproat e (VPA 1,000 mg/kg p.o. twice) also had no effect. Conclusions: ZNS at the anticonvulsant dose, unlike CBZ and VPA, ameliorated the brain in farction and the event of neurological deficit after transient focal c erebral ischemia. These data suggest that ZNS has therapeutic potentia l in protecting against ischemic cerebral damage, such as stroke.