Protective effect of zonisamide, an antiepileptic drug, against transient focal cerebral ischemia with middle cerebral artery occlusion-reperfusion in rats.
OBJECTIVE
The antiepileptic effects of zonisamide (ZNS) have been well documented experimentally and clinically. The purpose of this study was to examine whether ZNS reduces cerebral damage after transient focal ischemia in rats.


METHODS
Ischemia was induced by a transient occlusion of the left middle cerebral artery (MCA) with a 3-0 nylon monofilament for 90 min. Neurological evaluation was performed by measuring the event of neurological deficit of the contralateral forepaw and hindpaw at 10 min and 1 day after MCA occlusion (MCAo). Brain infarct size was determined by measuring triphenyltetrazonium chloride-negative stained 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 before and 4 h after or 15 min and 4 h after the occlusion] markedly reduced cerebral damage in the ipsilateral hemisphere and the neurological deficit induced by transient ischemia. The reducing effect on the damage was observed in the cortical and subcortical regions. Preischemic treatment with carbamazepine (CBZ 60 mg/kg p.o. twice 30 min before and 4 h after MCAo) tended to reduce the cerebral damage and neurological deficit, but the lower dose (20 mg/kg p.o. twice) did not. Valproate (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 infarction and the event of neurological deficit after transient focal cerebral ischemia. These data suggest that ZNS has therapeutic potential in protecting against ischemic cerebral damage, such as stroke.
Minato
H
H
Department of Pharmacology I, Discovery Research Laboratories I, Dainippon Pharmaceutical, Osaka, Japan.
Kikuta
C
C
Fujitani
B
B
Masuda
Y
Y
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D001157:Arterial Occlusive Diseases / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D001831:Body Temperature / Q000502:physiology; D002220:Carbamazepine / Q000494:pharmacology / Q000627:therapeutic use; D002539:Cerebral Arterial Diseases / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D002544:Cerebral Infarction / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D007555:Isoxazoles / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D014635:Valproic Acid / Q000494:pharmacology / Q000627:therapeutic use; D000078305:Zonisamide
D000927:Anticonvulsants; D007555:Isoxazoles; D002220:Carbamazepine; D000078305:Zonisamide; D014635:Valproic Acid