匹罗卡品致痫小鼠自发性癫痫发作模型的建立及癫痫后海马新生神经细胞增生的研究  

Hippocampal neurogenesis in a mouse model of temporal lobe epilepsy with spontaneous seizures

作　　者：李艺[1] 肖波[1] 杨欢[1] 龙莉莉[1] 冯莉[1] 陈锶[1] 方红军[1] 向田[1] 吴倩[1] 吴志国[1] 

机构地区：[1]中南大学湘雅医院神经内科,湖南省长沙市410008

出　　处：《国际神经病学神经外科学杂志》2011年第6期503-507,共5页Journal of International Neurology and Neurosurgery

基　　金：国家自然科学基金(81071048;81100967);高等学校博士学科点专项科研基金(20110162120002);中南大学中央高校基本科研业务费专项资金(2011QNZT152)

摘　　要：目的探讨匹罗卡品致痫小鼠自发性癫痫发作(SS)模型的特点,并观察癫痫发作后其齿状回颗粒细胞下层新生神经细胞(NPC)增生变化。方法建立SS小鼠模型,进行行为学检测。将SS发作小鼠在癫痫持续状态(SE)后不同时间点进行Doublecortin(DCX)免疫组化,Western blot观察海马NPC的分布和表达改变。结果 80%的模型小鼠出现持续SS,发作时程约10～40 s,发作频率为2.18±0.45次/周。DCX+细胞及其蛋白表达在模型组中显著增多(P<0.05),SE后4周最为明显,SE后8周开始下降,至SE后12周显著减少。增生的DCX+细胞呈簇状分布,随时间推移出现迁移分散。存在SS的模型小鼠相对于不存在SS的模型小鼠DCX+细胞增生更为明显。结论匹罗卡品致痫后SS小鼠模型存在持续的NPC增生,这可能在慢性期癫痫持续发作的病理生理机制中有着重要作用。Objective To explore the characteristics of a pilocarpine-induced mouse model of spontaneous seizures（SS）,and to observe the changes of neural progenitor cells（NPC） in the subgranular zone（SGZ） of dentate gyrus after seizure activities.Methods A pilocarpine-induced mouse model of spontaneous seizures was prepared.The behavioral characteristics were observed with continuous camera recording.The changes of NPC in the hippocampus were examined,with doubleortin（DCX） immunohistochemitry at different time points after status epilepticus（SE） in mice with continuous SS.The protein levels of DCX at different time points were determined by Western blot.Results Eighty percent of the mice with SE presented with SS.These mice began to show consistent SS after an average latent period of 3-10 days,which usually lasted 10-40 seconds at a frequency of 2.18±0.45 per week.Both the DCX-labeling cells and their protein expression increased in the SGZ of SS mice（P0.05）,peaked at 4 weeks after SE,and began to decrease at 8 weeks after SE.At 12 weeks after SE,the DCX-labeling cells and their protein expression were significantly reduced.The increased DCX＋ cells proliferated in clusters,and then migrated to different areas with the increasing time.The mice with continuous SS after SE had more increased DCX＋ cells in the SGZ than the mice without SS after SE.Conclusions The pilocarpine-incduced mouse model of SS showed continuous NPC proliferation,which may play an important role in epileptogenesis during the chronic period.

关 键 词：癫痫 自发性痫性发作 新生神经元 DOUBLECORTIN 小鼠 

分 类 号：R742.1[医药卫生—神经病学与精神病学]