Background Agrin is a proteoglycan that aggregates nicotinic acetylcholine receptors (AChRs) on neuromuscular junctions and takes part in synaptogenesis in the development of the central nervous system. However, its effects on neural repair and synaptogenesis after stroke are still unclear. Objective This study aimed to investigate the effects of agrin on neural repair and synaptogenesis after stroke and the effects of exercise on this process in vivo and in vitro. Methods Exercise with gradually increased intensity was initiated at 1 day after middle cerebral artery occlusion (MCAO) for a maximum of 14 days. Neurological deficit scores and foot fault tests were used to assess the behavioral recovery. Western blotting, immunofluorescence, and electron microscopic images were used to detect the expression of agrin, synaptogenesis-related proteins, and synaptic density in vivo. In vitro, the ischemic neuron model was established via oxygen-glucose deprivation (OGD). The lentivirus overexpressed agrin and CREB inhibitor were used to investigate the mechanism by which agrin promoted synaptogenesis. Results Exercise promoted behavioral recovery and this beneficial role was linked to the upregulated expression of agrin and increased synaptic density. Overexpressed agrin promoted synaptogenesis in OGD neuron, CREB inhibitor downregulated the expression of agrin and hampered synaptogenesis in cultured neurons. Conclusions These results indicated that exercise poststroke improved the recovery of behavioral function after stroke. Synaptogenesis was an important and beneficial factor, and agrin played a critical role in this process and could be a potential therapeutic target for the treatment of stroke and other nervous system diseases.

中文翻译：

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在实验性中风大鼠模型中运动诱导的集聚蛋白参与突触发生

背景 Agrin 是一种蛋白多糖，可在神经肌肉接头上聚集烟碱型乙酰胆碱受体 (AChR)，并参与中枢神经系统发育过程中的突触发生。然而，其对中风后神经修复和突触发生的影响仍不清楚。目的本研究旨在探讨集聚蛋白对脑卒中后神经修复和突触形成的影响以及运动对这一过程的体内外影响。方法在大脑中动脉闭塞（MCAO）后1天开始逐渐增加强度的运动，最多14天。神经功能缺损评分和足部缺陷测试用于评估行为恢复。Western印迹、免疫荧光和电子显微镜图像用于检测集聚蛋白、突触相关蛋白、和体内突触密度。在体外，缺血性神经元模型是通过氧糖剥夺（OGD）建立的。慢病毒过表达的集聚蛋白和 CREB ​​抑制剂被用来研究集聚蛋白促进突触发生的机制。结果锻炼促进行为恢复，这种有益作用与集聚蛋白表达上调和突触密度增加有关。过表达的集聚蛋白促进了 OGD 神经元的突触发生，CREB ​​抑制剂下调了集聚蛋白的表达并阻碍了培养神经元的突触发生。结论 这些结果表明，中风后运动可以改善中风后行为功能的恢复。突触发生是一个重要且有益的因素，