中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (6): 2397-2406.doi: 10.4103/NRR.NRR-D-24-00861

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

运动训练促进增强缺血性脑卒中后白质修复

  

  • 出版日期:2026-06-15 发布日期:2026-04-18

Physical exercise promotes white matter repair after ischemic stroke

Yating Mu#, Xiaofeng Yang#, Yifeng Feng, Liying Zhang, Jinghui Xu, Mingyue Li, Rui Wu, Shiying Li, Xiaofei He*, Zejie Zuo*, Xiquan Hu*   

  1. Department of Rehabilitation Medicine, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China
  • Online:2026-06-15 Published:2026-04-18
  • Contact: Xiquan Hu, PhD, huxiquan@mail.sysu.edu.cn; Zejie Zuo, PhD, zuozj3@mail.sysu.edu.cn; Xiaofei He, PhD, hexf33@mail.sysu.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 82172546 (to XH), 82172547 (to ZZ); the Natural Science Foundation of Guangdong Province, Nos. 2023A1515012695 (to XH), 2024A1515010419 (to ZZ); and the Science and Technology Plan Project of Guangzhou, Nos. 202201020413 (to ZZ), 2023A04J1099 (to ZZ).

PDF

1

摘要：

白质损伤是影响脑卒中康复的关键因素。据报道，运动训练可促进白质修复。免疫细胞，尤其是调节性T细胞，有助于增强白质的完整性，但对其机制尚知之甚少。为此，实验首先建立短暂性大脑中动脉闭塞小鼠模型，可见运动训练可增加大脑中调节性T细胞，促进神经恢复和髓鞘碎片清除，抑制神经炎症，加速白质修复。而当调节性T细胞被清除后，这种神经保护作用显著减弱。进一步研究发现，当调节性T细胞被耗竭时，运动训练诱导的高水平骨桥蛋白受到抑制。此外，调节性T细胞条件培养基还可减轻氧糖剥夺复氧诱导的小胶质细胞炎症，增强其吞噬作用，且这可被骨桥蛋白抗体所阻断。重要的是，尽管调节性T细胞再融合可模拟运动训练的保护作用，但阻断骨桥蛋白可部分抵消运动训练和调节性T细胞的作用。随后的测序结果显示，运动训练后CXCL12 mRNA表达明显上调，且这可在蛋白质水平上得到验证。最后，实验还显示，以脑卒中脑裂解物刺激调节性T细胞可增加CXCR4的表达，表明CXCL12-CXCR4轴在招募调节性T细胞中的潜在作用。上述结果表明，运动训练可通过调节性T细胞促进缺血性脑卒中后白质修复。


https://orcid.org/0000-0002-5554-6903 (Xiquan Hu); https://orcid.org/0000-0002-4035-8731 (Zejie Zuo); 

https://orcid.org/0000-0003-2983-0289 (Xiaofei He)

关键词: 运动训练, 缺血性脑卒中, 白质损伤, 调节性T细胞, 小胶质细胞, 神经炎症, 吞噬作用, 骨桥蛋白, CXCL12, 短暂性大脑中动脉闭塞

Abstract: White matter injury is a key factor impacting stroke recovery. Physical exercise can promote white matter repair. Immune cells, especially regulatory T (Treg) cells, contribute to strengthening white matter integrity, yet little is known about the underlying mechanism. To examine this, we established a transient middle cerebral artery occlusion male mouse model. We found that physical exercise elevated brain Treg cells, thereby enhancing neurological recovery, reducing neuroinflammation, promoting myelin debris clearance, and accelerating white matter repair. Depletion of Treg cells caused a decrease in these positive effects of physical exercise. Mechanistically, the rise in osteopontin triggered by physical exercise is dampened when Treg cells are depleted. In addition, Treg-conditioned medium reduced oxygen–glucose deprivation/re-oxygenation-induced microglial inflammation and enhanced phagocytosis, which could be blocked by osteopontin antibodies. Importantly, although Treg infusion could mimic the protective effects of physical exercise, osteopontin blockade partially countered the effects of physical exercise and Treg cells. Finally, our sequencing data revealed a marked upregulation of C–X–C motif chemokine ligand 12 (CXCL12) mRNA expression subsequent to physical exercise, which was confirmed at the protein level. Stimulation of Treg cells with stroke brain lysates increased C–X–C motif chemokine receptor 4 (CXCR4) expression, indicating a potential role for the CXCL12–CXCR4 axis in recruiting Treg cells. These findings suggest that physical exercise promotes white matter repair after ischemic stroke by Treg cells. 

Key words: CXCL12, ischemic stroke, microglia, neuroinflammation, osteopontin, phagocytosis, physical exercise, transient middle cerebral artery occlusion, Treg cells, white matter injury