Li Guo-Liang, Zhang Ning, Li Jing, Zhu Dan-Tong, Wu Zhi-Guo, Xiao Bo
Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2004 Aug;29(4):424-8.
To investigate the relationship between mossy fiber axon sprouting (MFS), synaptic reorganization in the dentate gyrus, and the mechanism of chronic temporal lobe epilepsy induced by pilocarpine.
The mossy fiber sprouting and synapse formation were observed in rats after the acute status epileticus and chronic spontaneous temporal lobe epilepsy induced by pilocarpine using in situ hybridization of GAP-43 mRNA (a marker of MFS), an immunohistochemical staining of synaptophysin (P38, a marker of synaptogenes), and Neo-Timm staining.
In hippocampus granule cell, there was a significant increase in the GAP-43mRNA levels measured 6 - 12 h after the end of status epileticus induced by pilocarpine. In contrast, synaptophysin immunoreactivity progressively increased in the molecular layer of the dentate gyrus from 7 d, which was in line with the Neo-Timm stain results that revealed a time-dependent growth of aberrant MFS into the dentate inner molecular layer. The GAP-43 mRNA levels in pilocarpine treated animals were significantly decreased after status epileticus.
These results provide evidence for newly formed excitatory recurrent circuits, which might constitute a structural basis for chronic enhanced excitation and epileptogenesis in the hippocampus of pilocarpine-treated rats.
探讨苔藓纤维轴突发芽(MFS)、齿状回突触重组与匹罗卡品诱导的慢性颞叶癫痫机制之间的关系。
采用GAP-43 mRNA原位杂交(MFS的标志物)、突触素免疫组化染色(P38,突触发生的标志物)和新Timm染色,观察匹罗卡品诱导大鼠急性癫痫持续状态和慢性自发性颞叶癫痫后苔藓纤维发芽和突触形成情况。
在海马颗粒细胞中,匹罗卡品诱导癫痫持续状态结束后6 - 12小时测量的GAP-43mRNA水平显著升高。相比之下,从第7天起,齿状回分子层的突触素免疫反应性逐渐增加,这与新Timm染色结果一致,即异常MFS向齿状回内分子层的生长呈时间依赖性。癫痫持续状态后,匹罗卡品处理动物的GAP-43 mRNA水平显著降低。
这些结果为新形成的兴奋性折返回路提供了证据,这可能构成匹罗卡品处理大鼠海马中慢性增强兴奋和癫痫发生的结构基础。