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皮质发育畸形大鼠的认知障碍与自发性癫痫

Cognitive impairment and spontaneous epilepsy in rats with malformations of cortical development.

作者信息

Ye-wei Xiao, Rong Wang, Xun-tai Ma, Shan Zhang, Qian Chen, Shi-hua Huang, Fu-qun Mao, Xiao-ming Xiong

机构信息

Department of Physiology, LuZhou Medical College, LuZhou, SiChuan Province 646000, P.R. China.

Department of Neurology, Affiliated Hospital of LuZhou Medical College, LuZhou, SiChuan Province 646000, P.R. China.

出版信息

Seizure. 2015 Dec;33:29-34. doi: 10.1016/j.seizure.2015.10.005. Epub 2015 Oct 17.

DOI:10.1016/j.seizure.2015.10.005
PMID:26540232
Abstract

PURPOSE

To examine the cognition, spontaneous epilepsy, and electroencephalography (EEG) characteristics of rats with malformations of cortical development (MCD) and their use as an animal model for investigating the pathogenesis of intractable epilepsy and screening novel antiepileptic drugs.

METHODS

An epileptic rat model of MCD was established with the F1 generation of pregnant rats after X-irradiation with 175 cGy (Group L), 195 cGy (Group M), or 215 cGy (Group H). Long-term video-EEG monitoring was used to record the seizures in the rats with MCD. Cognition was assessed with the Morris water maze. The EEGs were recorded and analyzed in the frontal and parietal lobes and hippocampi of adult rats. Finally, the brain tissues were processed for Nissl staining.

RESULTS

The model groups exhibited markedly prolonged escape latencies and distinct decrements in the percent distance traveled in the target quadrant and platform-crossing frequency. These findings were dose-dependent. Frequent interictal epileptiform discharges were observed in the frontal and parietal lobes and hippocampi of adult rats, and their incidences were markedly higher in the model groups compared with that in the normal controls, with Group M having the highest incidence. Spontaneous seizures were observed in the model groups (mean incidence, 46.7%). The daily mean frequency of seizures and the incidence of spontaneous seizures were highest in Group M. Nissl staining revealed a dose-dependent pattern of hippocampal abnormalities, cortical and subcortical nodular heterotopia, and callosal agenesis in the model groups.

CONCLUSION

The 195 cGy dose was most appropriate for establishing an epileptic model of MCD with X-irradiation.

摘要

目的

研究皮质发育畸形(MCD)大鼠的认知、自发性癫痫及脑电图(EEG)特征,及其作为难治性癫痫发病机制研究和新型抗癫痫药物筛选动物模型的应用。

方法

对怀孕大鼠F1代进行175 cGy(L组)、195 cGy(M组)或215 cGy(H组)的X射线照射,建立MCD癫痫大鼠模型。采用长期视频脑电图监测记录MCD大鼠的癫痫发作情况。用Morris水迷宫评估认知功能。记录并分析成年大鼠额叶、顶叶和海马的脑电图。最后,对脑组织进行尼氏染色处理。

结果

模型组大鼠的逃避潜伏期显著延长,目标象限内游动距离百分比和平台穿越频率明显降低。这些结果呈剂量依赖性。在成年大鼠的额叶、顶叶和海马中观察到频繁的发作间期癫痫样放电,模型组的发生率明显高于正常对照组,其中M组发生率最高。模型组观察到自发性癫痫发作(平均发生率为46.7%)。M组癫痫发作的日均频率和自发性癫痫发作的发生率最高。尼氏染色显示模型组海马异常、皮质和皮质下结节性异位及胼胝体发育不全呈剂量依赖性模式。

结论

195 cGy剂量最适合用X射线照射建立MCD癫痫模型。

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