Epileptogenic roles of astroglial death and regeneration in the dentate gyrus of experimental temporal lobe epilepsy
Epileptogenic roles of astroglial death and regeneration in the dentate gyrus of experimental temporal lobe epilepsy
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DOI：
10.1002/glia.20380
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发表时间：
2006-09-01
期刊：
影响因子：
6.2
通讯作者：
Kwon, Oh-Shin
中科院分区：
文献类型：
--
作者：
Kang, Tae-Cheon;Kim, Duk-Soo;Kwon, Oh-Shin
最近的研究表明，在各种癫痫模型中，阻断海马中的神经元死亡不能防止癫痫发生。这些报告表明，神经退行性病变本身不足以引起癫痫，星形胶质细胞在癫痫发生中的作用应重新考虑。因此，本研究的目的是阐明是否改变形态组织或功能的星形胶质细胞诱导癫痫持续状态（SE）是负责癫痫。神经胶质细胞反应（反应性小胶质细胞增生，然后星形胶质细胞死亡）在由匹鲁卡品诱导的SE诱导的齿状回被发现之前的神经元损伤，这些变化密切相关的异常神经传递相关的改变囊泡谷氨酸和GABA转运蛋白的表达，苔藓纤维发芽在齿状回。此外，新生成的星形胶质细胞表现出下调的谷氨酰胺合成酶，谷氨酸脱氢酶和神经胶质GABA转运蛋白的表达。两者合计，我们的研究结果表明，神经胶质反应后SE可能有助于癫痫的发生和收购的性质癫痫海马。因此，我们认为，这是值得考虑的新的治疗癫痫的方法，包括针对小胶质细胞的失活和防止星形胶质细胞的损失。(c)2006 whey-Liss，Inc.
Recent studies have demonstrated that blockade of neuronal death in the hippocampus cannot prevent epileptogenesis in various epileptic models. These reports indicate that neurodegeneration alone is insufficient to cause epilepsy, and that the role of astrocytes in epileptogenesis should be reconsidered. Therefore, the present study was designed to elucidate whether altered morphological organization or the functionalities of astrocytes induced by status epilepticus (SE) is responsible for epileptogenesis. Glial responses (reactive microgliosis followed by astroglial death) in the dentate gyrus induced by pilocarpine-induced SE were found to precede neuronal damage and these alterations were closely related to abnormal neurotransmission related to altered vesicular glutamate and GABA transporter expressions, and mossy fiber sprouting in the dentate gyrus. In addition, newly generated astrocytes showed down-regulated expressions of glutamine synthase, glutamate dehydrogenase, and glial GABA transporter. Taken together, our findings suggest that glial responses after SE may contribute to epileptogenesis and the acquisition of the properties of the epileptic hippocampus. Thus, we believe that it is worth considering new therapeutic approaches to epileptogenesis involving targeting the inactivation of microglia and protecting against astroglial loss. (c) 2006 whey-Liss, Inc.