Effects of detraining on preconditioning exercise-induced neuroprotective potential after ischemic stroke in rats
Effects of detraining on preconditioning exercise-induced neuroprotective potential after ischemic stroke in rats
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DOI：
10.1007/s00429-021-02317-5
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发表时间：
2021-06-10
影响因子：
3.1
通讯作者：
Maruyama, Ikuro
中科院分区：
文献类型：
--
作者：
Otsuka, Shotaro;Sakakima, Harutoshi;Maruyama, Ikuro
脑卒中前的预适应运动可发挥神经保护作用，这是一种内源性策略，可导致脑细胞表达多种内源性因子并抑制其凋亡。然而，目前还不清楚这些好处在运动停止后持续多久。本研究旨在探讨停训对脑卒中后运动预适应神经保护电位的影响。大鼠每周5天进行有氧运动训练，持续3周，并在运动停止后3周检查其神经保护作用。在运动停止后3天、1周、2周和3周，通过左侧大脑中动脉闭塞60分钟诱发中风。采用免疫组化和蛋白质印迹法检测脑体积、神经功能缺损、感觉运动功能、脑源性神经营养因子（BDNF）、缺氧诱导因子-1 α（HIF-1 α）、胶质细胞酸性蛋白（GFAP）和P2 X7受体的表达水平以及凋亡活性。预适应运动显著减少脑梗死体积，改善脑卒中后的感觉运动功能，其有益作用一直观察到运动停止后2周。在运动停止后3天，缺血脑中BDNF的表达水平显著上调;然而，HIF-1 α、GFAP和P2 X7受体的表达水平显著增加，直到运动停止后2周;因此，显著的抗凋亡作用在停训3周时丧失。我们的研究结果表明，预处理运动诱导的神经保护潜力可能会失去运动停止后不久。通过内源性保护因子如BDNF和HIF-1 α的神经保护作用可能在停训期间以时间依赖性方式提供不同的神经保护机制。
Preconditioning exercise prior to stroke exerts neuroprotection, which is an endogenous strategy that leads the brain cells to express several intrinsic factors and inhibits their apoptosis. However, it is unclear how long these benefits last after exercise cessation. The aim of this study was to investigate the effects of detraining on preconditioning exercise-induced neuroprotective potential after stroke. Rats were trained using a treadmill for aerobic exercise 5 days each week for 3 weeks, and their neuroprotective effects were examined until 3 weeks after exercise cessation. Stroke was induced by 60 min of left middle cerebral artery occlusion at 3 days, 1, 2, and 3 weeks after exercise cessation. Infarct volume, neurological deficits, sensorimotor function, expression levels of brain-derived neurotrophic factor (BDNF), hypoxia-induced factor-1 alpha (HIF-1 alpha), glial fibrillary acidic protein (GFAP), and P2X7 receptors, and apoptosis activity were examined using immunohistochemical and western blot analyses. Preconditioning exercise significantly reduced infarct volume and ameliorated sensorimotor function after stroke, and its beneficial effects were observed until 2 weeks after exercise cessation. The expression level of BDNF in the ischemic brain was significantly upregulated at 3 days after exercise cessation; however, the expression levels of HIF-1 alpha, GFAP, and P2X7 receptor were significantly increased until 2 weeks after exercise cessation; thereby, significant anti-apoptotic effects were lost at 3 weeks of detraining. Our findings suggest that preconditioning exercise-induced neuroprotective potential may be lost shortly after exercise cessation. Neuroprotection through intrinsic protective factors, such as BDNF and HIF-1 alpha, may provide different neuroprotective mechanisms in a time-dependent manner during detraining.