Pilocarpine诱导小鼠癫痫持续状态发作后海马神经元的兴奋激活、损伤和死亡(英文)

Neuron activation,degeneration and death in the hippocampus of mice after pilocarpine induced status epilepticus

目的:研究癫痫持续状态发作后海马神经元兴奋激活、细胞损伤和细胞死亡的发生和相互关系。方法:采用pilocarpine诱导Swiss小鼠癫痫持续状态(status epilepticus,SE)模型,分别以c-Fos,Fluoro JadeB和CFV染色分析SE后不同时间点齿状回和CA1区锥体细胞的兴奋激活、损伤和细胞存活状况。结果:在齿状回颗粒细胞层,c-Fos阳性细胞在SE后1,2和24 h增多(P<0.01或0.05),但各组齿状回颗粒细胞层均无明显Fluoro Jade B阳性细胞,CFV染色标记的阳性细胞数量在对照组和各实验组之间差异无统计学意义(P>0.05);门区神经元在SE后没有明显的c-Fos诱导表达,但SE后2和24 h,门区Fluoro Jade B阳性细胞数量较对照组增多(P<0.01),CFV染色显示SE后1 d门区残存的神经元数量较对照组减少(P<0.01);CA1区锥体细胞层c-Fos阳性细胞数量在SE后30 min,1,2和24 h后增多(P<0.01或0.05),Fluoro Jade B阳性细胞数量在SE后2和24 h也较对照组增多(P<0.01),但CFV染色CA1区锥体细胞数量在各组间差异无统计学意义(P>0.05)。结论:齿状回颗粒细胞、门区中间神经元以及CA1区锥体细胞在SE后的兴奋激活、颗粒细胞的损伤和死亡之间无直接的必然关系。

Objective To examine the occurrence of neuron activation, neurodegeneraion and cell death, and the correlation among them in the hippocampus after status epilepticus. Meth- ods CFV, Fluoro Jade B and c-Fos staining were done at multiple time points after pilocarpine induced status epilepticus. Results In the stratum granulosum of dentate gyms, c-Fos positive neu- rons increased significantly at 1 h, 2 h and 1 d after status epilepticus （P 〈 0.01 or 0.05 ）. However, almost no Fluoro Jade B staining cell was found in the stratum granulosum in the experiment and control groups, and no obvious difference was shown on the numbers of CFV staining cells in this area among all groups. In the hilus of dentate gyms of different groups, there were no c-Fos positive neurons in all groups. In the hilus, the number of Fluoro Jade B staining cells significantly increased at 2 h and 1 d after the status epileptieus （P 〈0.01 ）, and the number of CFV staining neurons dra- matically decreased 1 d after the status epilepticus （ P 〈 0.01 ） compared with the control. In the stratum pyramidale of CA1, the numbers of c-Fos positive neurons at 30 mim, 1 h, 2 h and 1 d, and Fluoro Jade B staining cells at 2 h and 1 d after the status epileptieus significantly increased （P 〈0.01 or 0.05） , while no obvious difference in the number of CFV staining cells in the stratum pyramidale of CA1 among different groups was shown. Conclusion There is no direct correlation among cell activation, neuron degeneration and cell death in the hippocampus of mice after pilocar- pine induced status epilepticus.