Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China; Department of Neurorehabilitation, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China.
Life Sci. 2021 Aug 1;278:119526. doi: 10.1016/j.lfs.2021.119526. Epub 2021 Apr 21.
White matter damage is the main pathological feature of chronic cerebral hypoperfusion (CCH) and glial activation is crucial in this process. Physical exercise has protective effects on CCH, but the mechanism is unclear. Therefore, this study focuses on investigating the influence of physical exercise on activated astrocytes polarization and its role in CCH.
Rats were given wheel running 48 h after 2VO (2 vessel occlusion) surgery. The cognitive function was evaluated by Morris water maze and novel object recognition test. Inflammatory cytokines expressions were detected by ELISA. Astrocytes polarization was analyzed by immunofluorescence. Myelin debris clearance and remyelination were detected by immunofluorescence and transmission electron microscopy.
Astrocytes were activated and mainly switched to A1 phenotype in rats 2 and 3 months after 2VO. Myelin debris deposition and limited remyelination can be observed at the corresponding time. Whereas physical exercise can improve the cognitive function of 2VO rats, downregulate the expression of inflammatory factors IL-1α, C1q and TNF, upregulate the release of TGFβ, and promote activated astrocytes transformation from A1 to A2 phenotype. In addition, it can also enhance myelin debris removal and remyelination.
These findings suggest that the benefits of physical exercise on white matter repair and cognition improvement may be related to its regulation of astrocytes polarization, which contributes to myelin debris clearance and effective remyelination in CCH.
脑白质损伤是慢性脑低灌注（CCH）的主要病理特征，胶质细胞激活在这一过程中至关重要。运动锻炼对 CCH 具有保护作用，但机制尚不清楚。因此，本研究重点探讨运动锻炼对激活星形胶质细胞极化的影响及其在 CCH 中的作用。
2VO（双血管闭塞）手术后 48 小时，大鼠进行转轮运动。通过 Morris 水迷宫和新物体识别测试评估认知功能。通过 ELISA 检测炎性细胞因子表达。通过免疫荧光分析星形胶质细胞极化。通过免疫荧光和透射电镜检测髓鞘碎片清除和髓鞘再生。
2VO 后 2 和 3 个月，大鼠星形胶质细胞被激活，并主要向 A1 表型转化。在相应时间点可观察到髓鞘碎片沉积和有限的髓鞘再生。而运动锻炼可以改善 2VO 大鼠的认知功能，下调炎性因子 IL-1α、C1q 和 TNF 的表达，上调 TGFβ的释放，并促进激活的星形胶质细胞从 A1 表型向 A2 表型转化。此外，它还可以增强髓鞘碎片的清除和髓鞘再生。
这些发现表明，运动锻炼对脑白质修复和认知改善的益处可能与其对星形胶质细胞极化的调节有关，这有助于 CCH 中髓鞘碎片的清除和有效的髓鞘再生。
