Neurogenesis promoted by the CD200/CD200R signaling pathway following treadmill exercise enhances post-stroke functional recovery in rats
Neurogenesis promoted by the CD200/CD200R signaling pathway following treadmill exercise enhances post-stroke functional recovery in rats
复制标题
跑步机运动后 CD200/CD200R 信号通路促进的神经发生可增强大鼠中风后功能恢复
DOI：
10.1016/j.bbi.2019.09.005
复制
发表时间：
2019-11-01
影响因子：
15.1
通讯作者：
Liao, Hong
中科院分区：
文献类型：
--
作者：
Sun, Hao;Li, Ao;Liao, Hong
中风是全世界长期残疾的主要原因；幸存者通常表现出感觉运动和认知缺陷。通过增强神经发生、血管生成、神经营养因子表达和突触发生，治疗性运动是卒中患者康复中最常见的治疗策略。神经发生在感觉运动和认知功能恢复中起重要作用，可通过运动促进；然而，这一现象背后的机制尚不清楚。在这项研究中，我们探讨了跑步机运动对大鼠短暂性大脑中动脉闭塞（tMCAO）模型的感觉运动和认知功能恢复的影响，以及促进神经发生的潜在分子机制。我们发现，跑步机运动促进了tMCAO后感觉运动和认知功能的恢复，并且tMCAO后同侧脑室下和颗粒下区神经干/祖细胞的增殖、分化和迁移增强。同时，在跑步机上运动诱导的新生神经元具有与已有神经元相似的功能。跑步机运动显著增加同侧海马和皮质中CD200和CD200受体（CD200R）水平。进一步的研究表明，在慢病毒（LV）诱导的脑卒中后CD200R表达抑制后，跑步机运动诱导的神经发生和功能恢复明显受到抑制，而il - β和tnf - α表达上调。与跑步机运动的效果一致，CD200Fc（一种CD200R激动剂）显著促进脑卒中后神经发生和功能恢复。此外，CD200Fc可进一步增强脑卒中后跑步机运动所致的功能恢复。我们的研究结果表明，跑步机运动通过激活CD200/CD200R信号通路和改善中风后的炎症环境，在促进神经发生和功能恢复方面具有有益作用。因此，CD200/CD200R信号通路是脑卒中后功能恢复的潜在治疗靶点。
Stroke is a leading cause of long-term disability worldwide; survivors often show sensorimotor and cognitive deficits. Therapeutic exercise is the most common treatment strategy for rehabilitating patients with stroke via augmentation of neurogenesis, angiogenesis, neurotrophic factors expression, and synaptogenesis. Neurogenesis plays important roles in sensorimotor and cognitive functional recovery, and can be promoted by exercise; however, the mechanism underlying this phenomenon remains unclear. In this study, we explored the effects of treadmill exercise on sensorimotor and cognitive functional recovery, as well as the potential molecular mechanisms underlying the promotion of neurogenesis in a rat model of transient middle cerebral artery occlusion (tMCAO). We found that treadmill exercise facilitated sensorimotor and cognitive functional recovery after tMCAO, and that neural stem/progenitor cell proliferation, differentiation, and migration were enhanced in the ipsilateral subventricular and subgranular zones after tMCAO. Meanwhile, the newborn neurons induced by treadmill exercise after tMCAO had the similar function with pre-existing neurons. Treadmill exercise significantly increased CD200 and CD200 receptor (CD200R) levels in the ipsilateral hippocampus and cortex. Further study revealed that treadmill exercise-induced neurogenesis and functional recovery were clearly inhibited, while Il-beta and Tnf-alpha expression were upregulated, following lentivirus (LV)-induced suppression of post-stroke CD200R expression. Consistent with the effect of treadmill exercise, CD200Fc (a CD200R agonist) markedly promoted neurogenesis and functional recovery after stroke. In addition, CD200Fc could further enhance the functional recovery induced by treadmill exercise after stroke. Our results demonstrate the beneficial role of treadmill exercise in promoting neurogenesis and functional recovery via activating the CD200/CD200R signaling pathway and improving the inflammatory environment after stroke. Thus, the CD200/CD200R signaling pathway is a potential therapeutic target for functional recovery after stroke.