mm staining was performed to evaluate mossy fiber sprouting and seizure susceptibility was tested by pentylenetetrazol( PTZ) at postnatal day 30. Results: Nissl staining showed that there was no obvious neuronal loss after seizure induction at either postnatal day 10 or postnatal day 30 in all groups. The degree of seizure and seizure susceptibility of rats in hypoxiaLTG group was similar to that in hypoxiaNS group. The seizure threshold induced by PTZ of the rats in hypoxiaLTG group was significantly higher than that in hypoxiaNS group(P<0.05) and lower than that in the two normoxia groups at postnatal day 30(P<0.01).There was no obvious difference between the two normoxia groups(P>0.05). Timm staining showed that supragranular zone of the dentate gyrus in hypoxiaLTG group was lower than that in hypoxiaNS group(P<0.05), but there was no obvious difference in the two normoxia groups at postnatal day 30. Conclusions: These results suggest that the potential neuroprotective effect of lamotrigine in these particular animal model of perinatal hypoxiainduced seizures. LTG decreased the longterm seizure susceptibility induced by chemical convulsant and prevented the later development of epilepsy.
[Key words] lamotrigine; neonatal rats; hypoxia; seizure; neuroprotective effects; mossy fiber sprouting
围产期缺氧是新生儿惊厥和新生儿脑病最常见的原因，对儿童的神经发育有潜在的长期影响，包括轻微的行为异常、严重的抽搐、智力发育迟滞和脑性麻痹等[1]。新生儿缺氧也是导致慢性癫痫的一个危险因素。而且，新生儿缺氧合并惊厥会使惊厥持续时间延长，甚至可能导致常规的抗惊厥治疗药物无效[2]。目前常用的抗痫药物，如巴比妥类、苯妥英那、苯二氮卓类，对发育脑都有副作用，所以我们需要寻找一种有效的、耐受性好、副作用少的新型抗痫药物来替代[3]。拉莫三嗪(lamotrigine，LTG)是一种新型抗癫痫药，有效应用于成人全身强直阵挛性抽搐，也用来辅助治疗癫痫或是作为单一的抗痫治疗药物。但国内外对LTG在新生期的应用鲜有研究，LTG对围生期缺氧惊厥大鼠的作用尚未报道。本实验制作了新生期缺氧性脑病模型，观察LTG是否可以降低缺氧惊厥新生大鼠的惊厥敏感性及从一定程度上阻止向癫痫发展的可能，是否具有神经保护作用。
1 材料与方法
1.1 动物模型制作和分组
10日龄同窝SD大鼠104只，雌雄不限，体质量14～18 g，由复旦大学提供鼠种，东南大学医学院实验动物中心繁殖。大鼠随机分成缺氧生理盐水组、缺氧LTG组、常氧生理盐水组和常氧LTG组4组。缺氧生理盐水组(n=26)：新生大鼠在缺氧前0.5 h预先腹腔注射生理盐水0.1 ml，然后根据逐步梯度降低氧浓度的方法造成急性缺氧的模型(在密闭装置中依次通入7%氧浓度8 min,7%～6%的氧浓度2
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