癲癇發(fā)作就像是雷暴雨在大腦中咆哮：神經(jīng)細(xì)胞彼此之間以一種不受控制的方法相互刺激,，以致于強(qiáng)大的有節(jié)奏的電釋放橫掃整個大腦區(qū)域,。癲癇發(fā)作的結(jié)果就是神經(jīng)細(xì)胞受到嚴(yán)重性影響，有可能導(dǎo)致永久性損傷,。一類包圍在大腦中神經(jīng)元周圍的細(xì)胞，即神經(jīng)膠質(zhì)細(xì)胞(glia cell),，長期被懷疑促進(jìn)癲癇發(fā)作導(dǎo)致的的損傷效應(yīng),。然而，來自德國弗萊堡大學(xué)伯恩斯坦中心的Carola Haas教授和來自弗萊堡大學(xué)解剖學(xué)與細(xì)胞生物學(xué)研究所的Matthias Kirsch博士領(lǐng)導(dǎo)的一個研究小組首次證實(shí),，情況剛好相反,。
在這項(xiàng)研究中，研究人員報(bào)道了,，一種特定類型的膠質(zhì)細(xì)胞---星形膠質(zhì)細(xì)胞(astrocyte)---的有益效果,。星形膠質(zhì)細(xì)胞長期被認(rèn)為能夠讓神經(jīng)細(xì)胞保持在一起,，并且給它們提供營養(yǎng)。當(dāng)癲癇發(fā)作時,，最流行的觀點(diǎn)是星形膠質(zhì)細(xì)胞對癲癇作出的反應(yīng)實(shí)際上給大腦造成損傷,。對此，來自弗萊堡大學(xué)的研究人員不同意,。他們說,，事實(shí)上，這些細(xì)胞有助于減少癲癇發(fā)作帶來的長期損傷,。
研究人員在小鼠體內(nèi)發(fā)現(xiàn)星形膠質(zhì)細(xì)胞的正面作用,，其中在小鼠體內(nèi)，癲癇狀態(tài)能夠被選擇性觸發(fā),。如果研究人員在癲癇誘導(dǎo)的損傷產(chǎn)生之前,，給小鼠注射一種特異性的蛋白來激活星形膠質(zhì)細(xì)胞，那么在癲癇發(fā)作時,，更少的神經(jīng)細(xì)胞死亡,，而且其他通常在大腦中發(fā)生的病理性變化也會類似地顯著性下降。在星形膠質(zhì)細(xì)胞被激活之后,，它們的保護(hù)效應(yīng)能夠持續(xù)數(shù)天時間,。當(dāng)研究人員測量了小鼠大腦活性，他們也類似地發(fā)現(xiàn)癲癇發(fā)作后,，大腦中出現(xiàn)的典型癥狀也減少了不少,。然而，研究人員報(bào)道,，在癲癇發(fā)作之前,，星形膠質(zhì)細(xì)胞就已經(jīng)被激活了。另一方面,，在癲癇發(fā)作之后,，激活星形膠質(zhì)細(xì)胞并不產(chǎn)生保護(hù)效應(yīng)。
這項(xiàng)研究提示著適時激活星形膠質(zhì)細(xì)胞可能提供一種有效的保護(hù)而使得大腦不用長期遭受損傷,。(生物谷：Bioon.com)
本文編譯自Astrocytes: More than just glue
doi: 10.1016/j.expneurol.2012.04.009
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PMID:
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.
