Yang Zhao, Zhong Lina, Zhong Shanchuan, Xian Ronghua, Yuan Bangqing
Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, China.
Department of Neurosurgery, The 476th Hospital of PLA, Fuzhou, Fujian 350025, China.
Exp Mol Pathol. 2015 Apr;98(2):219-24. doi: 10.1016/j.yexmp.2015.02.003. Epub 2015 Feb 7.
Much evidence demonstrated that autophagy played an important role in neural inflammation response after ischemia stroke. However, the specific effect of microglia autophagy in cerebral ischemia is still unknown. In the current study, we constructed focal cerebral ischemia model by permanent middle cerebral artery occlusion (pMCAO) in mice. We detected microglia autophagy and inflammation response in vivo, and observed infarct brain areas, edema formation, and neurological deficits of mice. We found that pMCAO induced microglia autophagy and inflammatory response. The suppression of autophagy using either pharmacologic inhibitor (3-MA) not only decreased the microglia autophagy and inflammatory response, but also significantly decreased infarct size, edema formation and neurological deficits in vivo. Taken together, these results suggested that cerebral ischemia induced microglia autophagy contributed to ischemic neural inflammation and injury. In addition, our findings also provided novel therapeutic strategy for ischemic stroke.
大量证据表明，自噬在缺血性中风后的神经炎症反应中起重要作用。然而，小胶质细胞自噬在脑缺血中的具体作用仍不清楚。在本研究中，我们通过永久性大脑中动脉闭塞（pMCAO）在小鼠中构建局灶性脑缺血模型。我们在体内检测小胶质细胞自噬和炎症反应，并观察小鼠的梗死脑区、水肿形成和神经功能缺损。我们发现pMCAO诱导小胶质细胞自噬和炎症反应。使用药理学抑制剂（3-MA）抑制自噬不仅降低了小胶质细胞自噬和炎症反应，而且在体内显著减小了梗死面积、水肿形成和神经功能缺损。综上所述，这些结果表明脑缺血诱导的小胶质细胞自噬促进了缺血性神经炎症和损伤。此外，我们的研究结果还为缺血性中风提供了新的治疗策略。
