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促红细胞生成素预处理可预防大鼠癫痫持续状态后的认知障碍。

Erythropoietin pre-treatment prevents cognitive impairments following status epilepticus in rats.

作者信息

Jun Yang, JiangTao Xu, YuanGui Huang, YongBin Song, Jun Zhen, XiaoJun Ma, JianChun Xu, Heng Xue, XiaoXin Zhang, XinXiang Xing

机构信息

Department of Neurology, Xin Jiang Urumqi Military General Hospital, No.41, Ke La Ma Yi Road, Urumqi 830000, China.

出版信息

Brain Res. 2009 Jul 28;1282:57-66. doi: 10.1016/j.brainres.2009.05.062. Epub 2009 Jun 2.

Abstract

Selective neuronal loss is closely associated with cognitive impairments that occur following status epilepticus (SE). Our previous study suggested that erythropoietin (Epo) pre-treatment suppressed hippocampal neuronal death in rats after 1 h of SE convulsions. However, the underlying protective mechanism remained unclear. In the present study, we investigated the anti-apoptotic mechanism of Epo pre-treatment in the hippocampus using Li-pilocarpine-induced SE in rats. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining was performed to detect apoptosis and the Morris water maze was employed to assess spatial learning ability and to analyze the protective effects of Epo. Levels of Bcl-2 family (Bid, Bcl-2 and Bax) markers were examined via Western blot and immunofluorescence. We found that Epo pre-treatment prevented SE-induced cognitive impairments. The protection and cognitive effects were associated with higher levels of Bcl-2 and lower levels of Bax. The present results suggest that systemic Epo pre-treatment can confer neuroprotection following SE, and may provide novel insights into pathogenesis and treatment following SE injury.

摘要

选择性神经元丢失与癫痫持续状态(SE)后出现的认知障碍密切相关。我们之前的研究表明,促红细胞生成素(Epo)预处理可抑制大鼠在SE惊厥1小时后海马神经元的死亡。然而,其潜在的保护机制仍不清楚。在本研究中,我们利用匹鲁卡品诱导的大鼠SE,研究了Epo预处理在海马中的抗凋亡机制。采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(TUNEL)染色检测细胞凋亡,并采用莫里斯水迷宫评估空间学习能力,分析Epo的保护作用。通过蛋白质免疫印迹和免疫荧光检测Bcl-2家族(Bid、Bcl-2和Bax)标志物的水平。我们发现,Epo预处理可预防SE诱导的认知障碍。这种保护和认知作用与较高水平的Bcl-2和较低水平的Bax有关。目前的结果表明,全身性Epo预处理可在SE后提供神经保护作用,并可能为SE损伤后的发病机制和治疗提供新的见解。

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