Minato H, Kikuta C, Fujitani B, Masuda Y
Department of Pharmacology I, Discovery Research Laboratories I, Dainippon Pharmaceutical, Osaka, Japan.
Epilepsia. 1997 Sep;38(9):975-80. doi: 10.1111/j.1528-1157.1997.tb01479.x.
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.
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.
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.
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.
唑尼沙胺（ZNS）的抗癫痫作用已在实验和临床中得到充分证明。本研究的目的是检验ZNS是否能减轻大鼠短暂性局灶性缺血后的脑损伤。
用3-0尼龙单丝短暂阻断大鼠左侧大脑中动脉（MCA）90分钟以诱导缺血。在MCA闭塞（MCAo）后10分钟和1天，通过测量对侧前爪和后爪神经功能缺损的情况进行神经学评估。在MCAo后1天，通过测量系列脑切片中氯化三苯基四氮唑阴性染色区域来确定脑梗死面积。
缺血前或缺血后用ZNS治疗（10-100mg/kg口服），即在闭塞前30分钟和闭塞后4小时或闭塞后15分钟和4小时给药，可显著减轻同侧半球的脑损伤以及短暂性缺血诱导的神经功能缺损。在皮质和皮质下区域均观察到对损伤的减轻作用。缺血前用卡马西平治疗（CBZ 60mg/kg口服，在MCAo前30分钟和后4小时各给药一次）有减轻脑损伤和神经功能缺损的趋势，但较低剂量（20mg/kg口服，给药两次）则无此作用。丙戊酸盐（VPA 1000mg/kg口服，给药两次）也无效果。
与CBZ和VPA不同，抗惊厥剂量的ZNS可改善短暂性局灶性脑缺血后的脑梗死和神经功能缺损情况。这些数据表明ZNS在预防缺血性脑损伤（如中风）方面具有治疗潜力。
