Neurogenesis and Proliferation of Neural Stem/Progenitor Cells Conferred by Artesunate via FOXO3a/p27Kip1 Axis in Mouse Stroke Model
Neurogenesis and Proliferation of Neural Stem/Progenitor Cells Conferred by Artesunate via FOXO3a/p27Kip1 Axis in Mouse Stroke Model
复制标题
青蒿琥酯通过 FOXO3a/p27Kip1 轴在小鼠中风模型中赋予神经干细胞/祖细胞的神经发生和增殖
DOI：
10.1007/s12035-021-02710-5
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发表时间：
2022-05-21
影响因子：
5.1
通讯作者：
Tan, Liang
中科院分区：
文献类型：
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作者：
Zhang, Kaiyuan;Yang, Yang;Tan, Liang
促进内源性神经干/祖细胞（NSPCs）的神经发生和增殖被认为是脑卒中后神经康复的一个有前途的策略。本实验室前期研究发现，中等剂量青蒿琥酯（ART，150 mg/ kg）可促进大脑中动脉闭塞（MCAO）小鼠的功能恢复。本研究旨在使用啮齿动物MCAO模型研究ART治疗对NSPCs神经发生和增殖的影响。MRI结果表明，ART治疗可减少MCAO小鼠的缺血脑体积。Tuj-1的扩散张量成像、电子显微镜和免疫荧光结果也显示ART治疗减轻了缺血诱导的白色物质损伤。缺血/再灌注后，ART治疗增加了同侧室下区和梗死周围皮质中Brdu +内源性NSPCs的比例。此外，ART的神经恢复作用被FOXO 3a的过表达所消除。这些结果表明，ART可以挽救缺血/再灌注损伤，减轻白色损伤，随后通过促进内源性NSPCs的神经发生和增殖，通过FOX 03 a/p27（Kip 1）通路，有助于脑卒中后功能恢复。
Promoting neurogenesis and proliferation of endogenous neural stem/progenitor cells (NSPCs) is considered a promising strategy for neurorehabilitation after stroke. Our previous study revealed that a moderate dose of artesunate (ART, 150 mg/ kg) could enhance functional recovery in middle cerebral artery occlusion (MCAO) mice. This study aimed to investigate the effects of ART treatment on neurogenesis and proliferation of NSPCs using a rodent MCAO model. MRI results indicated that the ischemic brain volume of MCAO mice was reduced by ART treatment. The results of diffusion tensor imaging, electron microscopic, and immunofluorescence of Tuj-1 also revealed that ischemia-induced white matter lesion was alleviated by ART treatment. After ischemia/reperfusion, the proportion of Brdu + endogenous NSPCs in the ipsilateral subventricular zone and peri-infarct cortex was increased by ART treatment. Furthermore, the neuro-restorative effects of ART were abolished by the overexpression of FOXO3a. These findings suggested that ART could rescue ischemia/reperfusion damage and alleviate white matter injury, subsequently contributing to post-stroke functional recovery by promoting neurogenesis and proliferation of endogenous NSPCs via the FOX03a/p27(Kip1) pathway.