Background 　Intractable epilepsy may be due to multidrug resistance induced by conventional antiepileptic drugs.The phenomenon is sometimes associated with an overexpression of multidrug resistance gene 1(MDR1).The purpose of this study was to determine if the over expression of MDR1 could be induced in a strocytes from ratbrains in vitro using antiepileptic drugs. Methods 　Astrocyte cell cultures from po stnatal Wistar rats(within 24 hours of birth)were established1 Different concentrations of the antiepileptic drugs phenytoin,phenobarbital,carbamazepine,and valproicacid were added to the cultures for 10,20,or 30 days.The expre ssion of P-glycoprotein(Pgp),the protein product of MDR1,was investigated with immunocytochemistry1 Results 　Less than 5 % of normal,untreated a strocyte s had detectable Pgp staining at any time point.Phenytoin,phenobarbital,carbamazepine,and valproic acid induced the overexpre ssion of Pgp in a strocyte s in a do se- and time-dependent manner.Significantly higher levels of Pgp staining were detected at therapeutic concentrations of certain antiepileptic drugs( 20 μg/ ml phenobarbital,40 μg/ ml phenobarbital,and 20μg/ ml phenytoin)on day 30 Upregulation of Pgp was detected when using higher concentrations of phenytoin,phenobarbital,and valproic acid on day 20 and when using higher concentrations of any of the four antiepileptic drugs on day 30. Conclusions Treatment with antiepileptic drugs may contribute to the overexpre ssion in a strocyte s of MDR1 and it s protein product,Pgp1 The mechanism leading to MDR must be considered in patient sundergoing long2term treatment with antiepileptic drugs.

Background Intractable epilep sy may be due to multidrug re sistance induced by conventional antiepileptic drugs1 The phenomenon is sometime s a ssociated with an overexpre ssion of multidrugre sistance gene 1(MDR1).The purpo se of this study wa s to determine if the overexpre ssionof MDR1 could be induced in a strocyte s from rat brains in vitro using antiepileptic drugs.Methods 　Astrocyte cell culture s from po stnatal Wistar rats (within 24 hours of birth)were e stablished.Different concentrations of the antiepileptic drugs phenytoin,phenobarbital,carbamazepine,and valproic acid were added to the culture s for 10,20,or 30 days.The expression of Pglycoprotein(Pgp),the protein product of MDR1,was inve stigated with immunocytochemistry.Results Less than 5 % of normal,untreated a strocytes had detectable Pgp staining at any time point.Phenytoin,phenobarbital,carbamazepine,and valproic acid induced the overexpre ssion of Pgp in a strocytes in a do se-and time2dependent manner.Significantly higher levels of Pgp staining were detected at therapeutic concentrations of certain antiepileptic drugs(20 μg/ ml phenobarbital,40 μg/ m.phenobarbital,and 20μg/ ml phenytoin)on day 301 Upregulation of Pgp was detected when using higher concentrations of phenytoin,phenobarbital,and valproic acid on day 20 and when using higher concentrations of any of the four antiepileptic drugs on day 30.Conclusions Treatment with antiepileptic drugs may contribute to the over expression in a strocytes of MDR1 and its protein product,Pgp.Themechanism leading to MDR must be considered in patients undergoing long-term treatment with antiepileptic drugs.

目的 观察液氮损伤诱导皮质发育障碍大鼠脑皮质中谷氨酸的分布，探讨其与癫痫发生的关系。方法 实验随机分为液氯损伤组、假手术组和正常对照组，建立皮质发育障碍模型，常规HE和Nissl染色，免疫组织化学方法用SABC法。结果 在大鼠脑嘴尾方向形成了一小的脑回，小脑回Glu阳性着色细胞在损伤组较假手术组表达曾加，却无显著差异（q检验，P>0.05），然而在小脑回周围区Glu阳性细胞表达显著增加（q检验，P<0.05），其他脑皮质区没有明显改变。结论 小脑回周围兴奋性神经递质谷氨酸的增加可能是导致癫痫发生机制之一。

目的 探讨液氮损伤诱导局灶性皮质发育障碍大鼠海马形态学及苔藓纤维发芽的情况。方法 实验随机分为正常对照组、假手术组和液氮损伤组，建立局灶性皮质发育障碍动物模型，察看其行为改变；采用常规HE染色、Nissl染色和Timm's硫化银组织化学方法染色，肉眼和光镜下观察大鼠脑皮质形态变化，光镜下评估海马苔藓纤维发芽情况，各组数据取苔藓纤维发芽评分，采用非参数秩和Kruskal-Wallis H检验，组间两两比较用Nemenyi法。结果 液氮损伤组大鼠行为轻微改变，鼠脑嘴方向形成了一小的脑回，同侧海马CA3区有苔藓纤维发芽，而正常对照组和假手术组却没有。 结论 幼鼠早期液氮损伤可导致小脑回形成及海马CA3区苔藓纤维发芽。小脑回周围异常兴奋性突触环路和海马CA3区苔藓纤维发芽形成推测是局灶性皮质发育障碍导致癫痫发生的重要机制。

目的 建立Wistar人鼠大脑皮质发育障碍的动物模型。方法 采用γ-射线照射孕15d Wistar火鼠的方法制作皮质发育障碍动物模型。观察：（1）孕鼠后代皮质发育障碍的类型和发生率，病理检查大鼠大脑皮质和海马结构；（2）模型组和正常对照组大常活动能力及脑电图变化；（3）利用热水浴诱导惊厥发作，观察潜伏期；（4）采用Morris水迷宫法测试大鼠学习能力和空间记忆能力。结果 （1）模型组大鼠脑重量（932mg）低于正常对照组大鼠（1 300mg，P<O. 05），病理可见模型组大鼠脑皮质变薄，皮质层状结构紊乱，皮质下神经元早结节状异位，海马锥体神经元团状分布；（2）模型鼠日常活动能力较差；（3）模型组热水浴诱导惊厥发作的潜伏期缩短[两组大鼠分别为（3. 65±0.44） min、（4. 66±0.58） min，P<0.05]；（4）模型组水迷宫实验中寻找水下平台时间延长（P<0.05）。结论 用γ-射线照射胚胎15d大鼠可建立皮质发育障碍动物模型，其惊厥发作易感性增加，伴有认知功能障碍。