Pre- and posttreatment with edaravone protects CA1 hippocampus and enhances neurogenesis in the subgranular zone of dentate gyrus after transient global cerebral ischemia in rats.
Pre- and posttreatment with edaravone protects CA1 hippocampus and enhances neurogenesis in the subgranular zone of dentate gyrus after transient global cerebral ischemia in rats.
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DOI：
10.1177/1759091414558417
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发表时间：
2014
期刊：
影响因子：
4.7
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Lei S;Zhang P;Li W;Gao M;He X;Zheng J;Li X;Wang X;Wang N;Zhang J;Qi C;Lu H;Chen X;Liu Y
依达拉奉在临床上用于治疗急性脑梗死患者。然而，依达拉奉的双重应用对缺血后海马神经发生的影响仍然未知。在本研究中，我们探讨了依达拉奉治疗前和治疗后是否对短暂性全脑缺血大鼠模型海马颗粒下区神经干/祖细胞（NSPCs）有任何影响，并阐明了其作用的潜在机制。雄性Sprague-Dawley大鼠分为3组：假手术组（n = 15）、对照组（n = 15）和依达拉奉治疗组（n = 15）。用5-溴-2-脱氧尿苷标记新产生的细胞。免疫组织化学法用于检测神经发生。末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记法检测细胞凋亡。采用2，7-二氯荧光素二乙酸酯法检测体外培养的NSPCs中活性氧（ROS）的含量。通过Western blot分析定量缺氧诱导因子-1 α（HIF-1α）和切割的caspase-3蛋白。依达拉奉治疗显著增加了颗粒下区的NSPCs和新生神经元的数量（p <0.05）。依达拉奉治疗也减少了NSPCs的凋亡（p <0.01）。此外，依达拉奉治疗显著减少ROS的产生，抑制HIF-1α和切割的caspase-3蛋白的表达。这些结果表明，依达拉奉预处理和后处理通过保护海马中的NSPCs免于凋亡来增强神经发生，这可能是通过减少脑缺血后的ROS产生和抑制HIF-1α和切割的caspase-3的蛋白表达来介导的。
Edaravone is clinically used for treatment of patients with acute cerebral infarction. However, the effect of double application of edaravone on neurogenesis in the hippocampus following ischemia remains unknown. In the present study, we explored whether pre- and posttreatment of edaravone had any effect on neural stem/progenitor cells (NSPCs) in the subgranular zone of hippocampus in a rat model of transient global cerebral ischemia and elucidated the potential mechanism of its effects. Male Sprague-Dawley rats were divided into three groups: sham-operated (n = 15), control (n = 15), and edaravone-treated (n = 15) groups. Newly generated cells were labeled by 5-bromo-2-deoxyuridine. Immunohistochemistry was used to detect neurogenesis. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling was used to detect cell apoptosis. Reactive oxygen species (ROS) were detected by 2,7-dichlorofluorescien diacetate assay in NSPCs in vitro. Hypoxia-inducible factor-1α (HIF-1α) and cleaved caspase-3 proteins were quantified by western blot analysis. Treatment with edaravone significantly increased the number of NSPCs and newly generated neurons in the subgranular zone (p < .05). Treatment with edaravone also decreased apoptosis of NSPCs (p < .01). Furthermore, treatment with edaravone significantly decreased ROS generation and inhibited HIF-1α and cleaved caspase-3 protein expressions. These findings indicate that pre- and posttreatment with edaravone enhances neurogenesis by protecting NSPCs from apoptosis in the hippocampus, which is probably mediated by decreasing ROS generation and inhibiting protein expressions of HIF-1α and cleaved caspase-3 after cerebral ischemia.
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影响因子：
82.9
作者：
Eriksson, PS;Perfilieva, E;Gage, FH
通讯作者：
Gage, FH
DOI：
10.1016/j.bbrc.2009.09.015
发表时间：
2009-12-25
影响因子：
3.1
作者：
Kikuchi, Kiyoshi;Tancharoen, Salunya;Kawahara, Ko-ichi
通讯作者：
Kawahara, Ko-ichi
影响因子：
5
作者：
Amemiya, S;Kamiya, T;Katayama, Y
通讯作者：
Katayama, Y
影响因子：
2.5
作者：
Brown, JP;Couillard-Després, S;Kuhn, HG
通讯作者：
Kuhn, HG
影响因子：
3.2
作者：
Lautraite, S;Bigot-Lasserre, D;Carmichael, N
通讯作者：
Carmichael, N