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首页 » BIOON报道 » Exp Neurol:首次证实星形胶质细胞也能降低癫痫发作所带来的大脑损伤

Exp Neurol:首次证实星形胶质细胞也能降低癫痫发作所带来的大脑损伤

来源:生物谷 2012-08-08 22:28

癫痫发作就像是雷暴雨在大脑中咆哮:神经细胞彼此之间以一种不受控制的方法相互刺激,以致于强大的有节奏的电释放横扫整个大脑区域。癫痫发作的结果就是神经细胞受到严重性影响,有可能导致永久性损伤。一类包围在大脑中神经元周围的细胞,即神经胶质细胞(glia cell),长期被怀疑促进癫痫发作导致的的损伤效应。然而,来自德国弗莱堡大学伯恩斯坦中心的Carola Haas教授和来自弗莱堡大学解剖学与细胞生物学研究所的Matthias Kirsch博士领导的一个研究小组首次证实,情况刚好相反。

在这项研究中,研究人员报道了,一种特定类型的胶质细胞---星形胶质细胞(astrocyte)---的有益效果。星形胶质细胞长期被认为能够让神经细胞保持在一起,并且给它们提供营养。当癫痫发作时,最流行的观点是星形胶质细胞对癫痫作出的反应实际上给大脑造成损伤。对此,来自弗莱堡大学的研究人员不同意。他们说,事实上,这些细胞有助于减少癫痫发作带来的长期损伤。

研究人员在小鼠体内发现星形胶质细胞的正面作用,其中在小鼠体内,癫痫状态能够被选择性触发。如果研究人员在癫痫诱导的损伤产生之前,给小鼠注射一种特异性的蛋白来激活星形胶质细胞,那么在癫痫发作时,更少的神经细胞死亡,而且其他通常在大脑中发生的病理性变化也会类似地显著性下降。在星形胶质细胞被激活之后,它们的保护效应能够持续数天时间。当研究人员测量了小鼠大脑活性,他们也类似地发现癫痫发作后,大脑中出现的典型症状也减少了不少。然而,研究人员报道,在癫痫发作之前,星形胶质细胞就已经被激活了。另一方面,在癫痫发作之后,激活星形胶质细胞并不产生保护效应。

这项研究提示着适时激活星形胶质细胞可能提供一种有效的保护而使得大脑不用长期遭受损伤。(生物谷:Bioon.com)

本文编译自Astrocytes: More than just glue

CNTF-mediated preactivation of astrocytes attenuates neuronal damage and epileptiform activity in experimental epilepsy

Matthias Bechsteina, 1, Ute Häusslera, 1, Matthias Neefa, Hans-Dieter Hofmannb, Matthias Kirschb, 1, Carola A. Haas

Activated astrocytes display a broad spectrum of properties, ranging from neuroprotection to active contribution to demise of neural tissue. To investigate if activation of astrocytes by a single, defined stimulus enhances neuroprotective properties, we tested whether injection of ciliary neurotrophic factor (CNTF) can ameliorate epilepsy-related brain damage. Intrahippocampal CNTF injection in mice induced a rapid (within 2 days) and persistent (3 weeks) activation of astrocytes reflected by strong upregulation of glial fibrillary acidic protein (GFAP) mRNA synthesis and GFAP immunoreactivity. Moreover, CNTF signaling via phosphorylation and nuclear translocation of STAT3 (signal transducer and activator of transcription 3) was specifically activated in GFAP-positive astrocytes. CNTF-mediated activation of astrocytes 2 days prior to an epileptogenic intrahippocampal injection of kainate (KA) resulted in strongly reduced cell death in the hilus and CA3 region of the hippocampus, revealed by Fluoro-Jade B staining. Granule cell dispersion, the pathological widening of the granule cell layer, was also significantly reduced 16 days after KA injection. Importantly, intrahippocampal in vivo recordings 3 weeks after KA injection showed that the occurrence of high frequency oscillations (fast ripples, FR), a surrogate marker for epileptic activity, was significantly reduced in CNTF + KA-injected mice as compared to KA-injected animals. However, when CNTF was applied in the chronic epileptic phase at 3 weeks after KA injection, no reduction of FR activity was observed. In summary, our results indicate that the activation of astrocytes prior to an excitotoxic injury effectively reduces neuronal damage and the severity of epileptiform activity, whereas activation in the chronic phase is no longer protective.

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