Xu Ming-Shu, Yin Lei-Miao, Cheng Ai-Fang, Zhang Ying-Jie, Zhang Di, Tao Miao-Miao, Deng Yun-Yi, Ge Lin-Bao, Shan Chun-Lei
Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Shanghai Research Institute of Acupuncture and Meridian, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Front Cell Dev Biol. 2021 Mar 11;9:634347. doi: 10.3389/fcell.2021.634347. eCollection 2021.
Cerebral ischemia is one of the leading causes of death. Reperfusion is a critical stage after thrombolysis or thrombectomy, accompanied by oxidative stress, excitotoxicity, neuroinflammation, and defects in synapse structure. The process is closely related to the dephosphorylation of actin-binding proteins (e.g., cofilin-1) by specific phosphatases. Although studies of the molecular mechanisms of the actin cytoskeleton have been ongoing for decades, limited studies have directly investigated reperfusion-induced reorganization of actin-binding protein, and little is known about the gene expression of actin-binding proteins. The exact mechanism is still uncertain. The motor cortex is very important to save nerve function; therefore, we chose the penumbra to study the relationship between cerebral ischemia-reperfusion and actin-binding protein. After transient middle cerebral artery occlusion (MCAO) and reperfusion, we confirmed reperfusion and motor function deficit by cerebral blood flow and gait analysis. PCR was used to screen the high expression mRNAs in penumbra of the motor cortex. The high expression of cofilin in this region was confirmed by immunohistochemistry (IHC) and Western blot (WB). The change in cofilin-1 expression appears at the same time as gait imbalance, especially maximum variation and left front swing. It is suggested that cofilin-1 may partially affect motor cortex function. This result provides a potential mechanism for understanding cerebral ischemia-reperfusion.
脑缺血是主要死因之一。再灌注是溶栓或取栓后的关键阶段，伴有氧化应激、兴奋性毒性、神经炎症以及突触结构缺陷。该过程与特定磷酸酶使肌动蛋白结合蛋白（如丝切蛋白-1）去磷酸化密切相关。尽管对肌动蛋白细胞骨架分子机制的研究已持续数十年，但直接研究再灌注诱导的肌动蛋白结合蛋白重组的研究有限，对肌动蛋白结合蛋白的基因表达了解甚少。确切机制仍不确定。运动皮层对于挽救神经功能非常重要；因此，我们选择半暗带研究脑缺血再灌注与肌动蛋白结合蛋白之间的关系。短暂大脑中动脉闭塞（MCAO）及再灌注后，我们通过脑血流和步态分析确认了再灌注及运动功能缺损。采用PCR筛选运动皮层半暗带中高表达的mRNA。通过免疫组织化学（IHC）和蛋白质免疫印迹法（WB）证实该区域丝切蛋白高表达。丝切蛋白-1表达的变化与步态失衡同时出现，尤其是最大变化和左前摆动。提示丝切蛋白-1可能部分影响运动皮层功能。该结果为理解脑缺血再灌注提供了潜在机制。
