托吡酯长期应用对癫痫幼鼠学习记忆及海马NMDAR1 mRNA表达的影响

目的:研究托吡酯(TPM)长期应用对癫癎幼鼠学习记忆功能的影响,并观察海马NMDAR1 mRNA表达的变化。方法:以锂-匹罗卡品制作癫癎模型,TPM灌胃,5周后使用Morris水迷宫评价大鼠的学习记忆功能,通过核酸原位杂交法观察海马各区NMDAR1mRNA表达的变化。结果:癫癎幼鼠的学习记忆功能较正常幼鼠明显下降;癫癎幼鼠学习记忆功能经中、小剂量TPM干预后未发生变化,而经大剂量TPM于预后则明显下降;大鼠海马各区NMDAR1 mRNA的表达在TPM干预后无明显变化。结论:癫癎持续状态(SE)后的慢性癫癎对幼鼠的视觉空间学习记忆功能造成损害,长期大剂量应用TPM可加重这一损害,该损害可能与海马CA1、CA3区NMDAR1 mRNA的表达无关。

Effect of Long-term Topiramate Treatment on Cognition and Hippocampal NMDAR1 mRNA Expression in Chronic Epileptic Immature Rats

Aim: To investigate the alteration of cognitive function and the role of N-methyl-D-asparate receptor subtype 1 (NMDAR1) in hippocampus in chronic epileptic rats during development exposed to long-term topiramate treatment.Methods: Chronic epileptic models were elicited by lithium-pilocarpine.Topiramate were administered intragastrically following status epilepticus (SE) for 5 weeks. Visual-spatial cognitive function performance was assessed with Morris water maze test after completion of the topiramate treatment. In situ hybridization was used to determine the changes of seizure-induced NMDARl mRNA expression in hippocampus. Results: Significant cognitive dysfunction was observed in epileptic rats. Model rats treated with low and raoderate-dose topiramate showed no difference in cognivive function compared with epileptic rats without topiramate treatment,however,high-dose topiramate appeared to impair the cognitvie performance of epileptic rats. No difference in NMDARl mRNA expression was found in hippocampus. Conclusion: The data implied that there are cognitive impairment in chronic epileptic rats following SE. Long-term administration of high-dose topiramate appears to aggravate the cognitive dysfunction of epileptic rats. It seems the changes of NMDARl mRNA expression in hippocampus is not the key reason of cognitvie impairment in clironic epileptic rats following SE.