Effects of Treadmill Exercise on Motor and Cognitive Function Recovery of MCAO Mice Through the Caveolin-1/VEGF Signaling Pathway in Ischemic Penumbra
Effects of Treadmill Exercise on Motor and Cognitive Function Recovery of MCAO Mice Through the Caveolin-1/VEGF Signaling Pathway in Ischemic Penumbra
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DOI：
10.1007/s11064-019-02728-1
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发表时间：
2019-04-01
影响因子：
4.4
通讯作者：
Chen, Xiang
中科院分区：
文献类型：
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作者：
Chen, Zhenzhen;Hu, Quan;Chen, Xiang
运动被认为是促进卒中后运动和认知功能恢复的一种有效的康复策略，尽管运动诱导的脑缺血损伤修复的复杂效应尚未完全阐明。适度运动促进血管生成和神经再生，改善突触可塑性，有利于脑缺血损伤后功能的恢复。我们以前的研究已经证实了小窝蛋白-1/血管内皮生长因子途径在大脑中动脉阻塞大鼠的血管生成和神经发生中的作用。脑源性神经营养因子作为一种重要的神经营养因子，在缺血性损伤中具有多方面的作用。在本研究中，我们试图通过与脑源性神经营养因子相关的小窝蛋白-1/血管内皮生长因子通路来确定跑步机运动介导的运动和认知功能恢复的另一种机制。结果发现，运动组小鼠大脑中动脉闭塞后小窝蛋白-1、血管内皮生长因子、脑源性神经营养因子、突触素I和细胞色素P4受体1的表达显著上调，BrdU/CD34、BDNF、BrdU/Neun、BrdU/突触素I和细胞色素P4受体1的阳性细胞数增加，支持神经功能缺失和脑梗塞体积的减少，以及突触形态和空间学习能力的改善。然而，小窝蛋白-1抑制剂大豆苷元导致神经功能缺失和脑梗塞体积增加。选择性的VEGFR2抑制剂PD173074可显著增加脑缺血半暗带的脑梗塞体积和神经功能损伤，减少BDNF的表达。这些发现表明，运动改善血管生成、神经再生和突触可塑性，部分是通过小窝蛋白-1/血管内皮生长因子途径改善卒中后的运动和认知障碍，该通路与辅助调节因子BDNF有关。
Exercise has been regarded as an effective rehabilitation strategy to facilitate motor and cognitive functional recovery after stroke, even though the complex effects associated with exercise-induced repair of cerebral ischemic injury are not fully elucidated. The enhancement of angiogenesis and neurogenesis, and the improvement of synaptic plasticity following moderate exercise are conducive to functional recovery after ischemic damage. Our previous studies have confirmed the angiogenesis and neurogenesis through the caveolin-1/VEGF pathway in MCAO rats. As an essential neurotrophic factor, BDNF has multiple effects on ischemic injury. In this study, we attempted to determine an additional mechanism of treadmill exercise-mediated motor and cognitive functional recovery through the caveolin-1/VEGF pathway associated with BDNF in the ischemic penumbra of MCAO mice. We found that mice exposed to treadmill exercise after the MCAO operation showed a significant up-regulation in expression of caveolin-1, VEGF, BDNF, synapsin I and CYFIP1 proteins, numbers of cells positive for BrdU/CD34, BDNF, BrdU/NeuN, BrdU/Synapsin I and CYFIP1 expression were increased, which support the reduction in neurological deficit and infarction volume, as well as improved synaptic morphology and spatial learning abilities, compared with the non-exercise mice. However, the caveolin-1 inhibitor, daidzein, resulted in increase in neurological deficit and infarction volume. The selective VEGFR2 inhibitor, PD173074, significantly induced larger infarction volume and neurological injury, and decreased the expression of BDNF in the ischemic penumbra. These findings indicate that exercise improves angiogenesis, neurogenesis and synaptic plasticity to ameliorate motor and cognitive impairment after stroke partially through the caveolin-1/VEGF pathway, which is associated with the coregulator factor, BDNF.