Time-course of neuronal death in the mouse pilocarpine model of chronic epilepsy using Fluoro-Jade C staining
Time-course of neuronal death in the mouse pilocarpine model of chronic epilepsy using Fluoro-Jade C staining
复制标题
使用 Fluoro-Jade C 染色观察慢性癫痫小鼠毛果芸香碱模型中神经元死亡的时间进程
DOI：
10.1016/j.brainres.2008.07.097
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发表时间：
2008-11-19
期刊：
影响因子：
2.9
通讯作者：
Chen, Liang-Wei
中科院分区：
文献类型：
--
作者：
Wang, Lian;Liu, Yong-Hong;Chen, Liang-Wei
癫痫是一种严重的神经系统疾病，其长期的病理过程尚不清楚。我们有兴趣在阐明长期的脑损伤，可能会发生在颞叶癫痫，和神经元死亡的时间过程中进行了检查，在小鼠匹鲁卡品模型的慢性癫痫的Fluoro-Jade C（FJC）染料，可以特异性地染色变性神经元在中枢神经系统。FJC染色结合神经元核特异性蛋白免疫组化显示，匹罗卡品致癫痫持续状态（SE）后，脑内神经元大量变性死亡，密集分布于大脑皮质和海马。FJC阳性变性神经元在SE发生后4 h出现，12 h ~ 3d达高峰，7 d ~ 14 d逐渐下降，多数神经元同时表达凋亡信号分子caspase-9和活化caspase-3。更有趣的是，大百分比（约88%）的FJC阳性变性神经元是GABA能的，如它们对谷氨酸脱羧酶-67的免疫反应性所示，这意味着在这种小鼠毛果芸香碱模型中，遭受SE攻击的脑中GABA能神经系统的抑制功能可能受到严重损害。结合前人的研究，Fluoro-Jade C染色法研究小鼠匹罗卡品模型中神经元变性的时间进程，有助于进一步了解脑的长期病理变化和反复发作的机制，并可能为人类慢性癫痫的治疗操作寻找最合适的时间窗。(C)2008由爱思唯尔公司出版
Epilepsy is a serious neurological disorder in human beings and the long-term pathological events remain largely obscure. We are interested in elucidating long-term brain injury that may occur in the temporal lobe epilepsy, and time-course of neuronal death was examined in a mouse pilocarpine model of chronic epilepsy by Fluoro-Jade C (FJC) dye that can specifically stain the degenerative neurons in the central nervous system. The FJC stain combined with immunohistochemistry to neuronal nuclear specific protein revealed that pilocarpine-induced status epilepticus (SE) resulted in massive degenerative death of neuronal cells in brains with their dense distribution in the cerebral cortex and hippocampus. The FJC-positive degenerating neurons, most of them also expressed apoptosis signaling molecules such as caspase-9 and activated caspase-3, occur-red at 4h, increased into peak levels at 12h-3d, and then gradually went down at 7d-14d after onset of SE. More interestingly, a large percentage (about 88%) of FJC-positive degenerative neurons were GABAergic as indicated with their immunoreactivity to glutamic acid decarboxylase-67, implying that inhibitory function of GABAergic neural system might by seriously damaged in brains subject to SE attack in this mouse pilocarpine model. Taken together with previous studies, time-course of degenerative neurons in the mouse pilocarpine model by Fluoro-Jade C staining further benefits understanding of long-term brain pathological changes and recurrent seizure mechanism, and may also result in finding the most suitable time-window in therapeutic manipulation of the chronic epilepsy in human beings. (C) 2008 Published by Elsevier B.V.