Spontaneous functional recovery occurs during the acute phase after stroke onset, but this intrinsic recovery remains limited. Therefore, exploring the mechanism underlying spontaneous recovery and identifying potential strategies to promote functional rehabilitation after stroke are very important. The CD200/CD200R signaling pathway plays an important role in neurological recovery by modulating synaptic plasticity during multiple brain disorders. However, the effect and mechanism of action of the CD200/CD200R pathway in spontaneous functional recovery after stroke are unclear. In this study, we used a transient middle cerebral artery occlusion (MCAO) model in rats to investigate the function of CD200/CD200R signaling in spontaneous functional recovery after stroke. We performed a battery of behavioral tests (Longa test, adhesive removal test, limb-use asymmetry test, and the modified grip-traction test) to evaluate sensorimotor function after intracerebroventricular (i.c.v.) injection with CD200 fusion protein (CD200Fc) or CD200R blocking antibody (CD200R Ab) post-stroke. Density and morphology of dendritic spines were analyzed by Golgi staining. Microglia activation was evaluated by immunofluorescence staining. Western blot was used to detect the levels of protein and the levels of mRNA were measured by qPCR. Our study demonstrated that sensorimotor function, synaptic proteins, and structures were gradually recovered and CD200R was transiently upregulated in ipsilateral cortex after stroke. Synapse-related proteins and dendritic spines were preserved, accompanied by sensorimotor functional recovery, after stereotaxic CD200Fc injection post-stroke. In addition, CD200Fc restrained microglia activation and pro-inflammatory factor release (such as Il-1, Tnf-α, and Il-6) after MCAO. On the contrary, CD200R Ab aggravated sensory function recovery in adhesive removal test and further promoted microglia activation and pro-inflammatory factor release (such as Il-1) after MCAO. The immune-modulatory effect of CD200/CD200R signaling might be exerted partly by its inhibition of the MAPK pathway. This study provides evidence that the CD200/CD200R signaling pathway contributes to spontaneous functional recovery by enhancing synaptic plasticity via inhibition of microglia activation and inflammatory factor release.

中文翻译：

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CD200 / CD200R信号通路通过增强中风后突触可塑性来促进自发功能恢复。

自发的功能恢复发生在中风发作后的急性期，但是这种固有的恢复仍然受到限制。因此，探索自发恢复的机制并确定促进中风后功能康复的潜在策略非常重要。CD200 / CD200R信号通路通过调节多种脑部疾病中的突触可塑性在神经系统恢复中发挥重要作用。但是，尚不清楚CD200 / CD200R途径在中风后自发功能恢复中的作用和作用机理。在这项研究中，我们在大鼠中使用了瞬态大脑中动脉闭塞（MCAO）模型来研究CD200 / CD200R信号传导在中风后自发功能恢复中的功能。我们进行了一系列行为测试（龙加测试，脱胶测试，肢体不对称测试和改良的抓地力测试）以评估脑卒中后脑室内（icv）注射CD200融合蛋白（CD200Fc）或CD200R阻断抗体（CD200R Ab）的感觉运动功能。通过高尔基染色分析树突棘的密度和形态。通过免疫荧光染色评估小胶质细胞的活化。用蛋白质印迹法检测蛋白质水平，并通过qPCR测量mRNA水平。我们的研究表明，卒中后同侧皮质的感觉运动功能，突触蛋白和结构逐渐恢复，CD200R瞬时上调。脑卒中后进行立体定向CD200Fc注射后，突触相关蛋白和树突棘得以保留，并伴有感觉运动功能恢复。此外，CD200Fc抑制了MCAO后小胶质细胞的活化和促炎因子的释放（例如Il-1，Tnf-α和Il-6）。相反，在MCAO后，CD200R Ab加剧了粘着剂去除测试中的感觉功能恢复，并进一步促进了小胶质细胞的活化和促炎因子的释放（例如Il-1）。CD200 / CD200R信号传导的免疫调节作用可能部分是通过抑制MAPK途径发挥的。这项研究提供了CD200 / CD200R信号通路通过抑制小胶质细胞活化和炎性因子释放来增强突触可塑性，从而促进自发功能恢复的证据。在MCAO后，CD200R Ab加剧了粘着剂去除测试中的感觉功能恢复，并进一步促进了小胶质细胞的活化和促炎因子的释放（例如Il-1）。CD200 / CD200R信号传导的免疫调节作用可能部分是通过抑制MAPK途径发挥的。这项研究提供了CD200 / CD200R信号通路通过抑制小胶质细胞活化和炎性因子释放来增强突触可塑性，从而促进自发功能恢复的证据。在MCAO后，CD200R Ab加剧了粘着剂去除测试中的感觉功能恢复，并进一步促进了小胶质细胞的活化和促炎因子的释放（例如Il-1）。CD200 / CD200R信号传导的免疫调节作用可能部分是通过抑制MAPK途径发挥的。这项研究提供了CD200 / CD200R信号通路通过抑制小胶质细胞活化和炎性因子释放来增强突触可塑性，从而促进自发功能恢复的证据。