上睑下垂
创伤性脑损伤
炎症体
小胶质细胞
神经保护
免疫印迹
血脑屏障
半胱氨酸蛋白酶1
下调和上调
医学
神经炎症
神经科学
缺氧(环境)
炎症
化学
免疫学
药理学
生物
中枢神经系统
精神科
生物化学
氧气
有机化学
基因
作者
Yuan Dong,Shuangxian Guan,Zhen Wang,HongLiang Ni,Dongliang Ding,Wenbo Xu,Guomin Li
标识
DOI:10.1016/j.jchemneu.2021.101994
摘要
Hypoxia inducible factor 1 alpha (HIF-1α) is involved in regulating the biological functions of neuronal death after traumatic brain injury (TBI), and attaches importance in the inflammatory response, but its potential mechanism is still unknown. Our study aimed to explore the regulatory mechanism between HIF-1α and NLRP3 inflammasome after TBI. Male mice underwent controlled cortical impact (CCI) or sham-operated procedures. Brain water content and blood-brain barrier permeability were measured at the indicated time after TBI. The behavioral performance, ELISA, immunofluorescence, and western blot analysis were used to determine whether HIF-1α specifically targeted TBI-induced pyroptosis. We discovered that TBI-induced brain injury caused by external mechanical forces is characterized by edema and blood-brain barrier disorder, and the release of IL-1β, IL-18, and LDH and upregulation of HIF-1α expression, reaching the peak on the third day post-TBI. In addition, HIF-1α accumulated NLRP3 inflammasome-mediated pyroptosis and activation of microglia. The protein expressions of NLRP3, GSDMD, GSDMD-N, pro-caspase 1, and cleaved caspase 1 were markedly increased in the injured cortex, which were restored to normal levels by the interference of HIF-1α. The inactivation of HIF-1α conferred neuroprotection and alleviated brain injury after TBI. HIF-1α was implicated in TBI-induced brain injury, aggravated NLRP3 inflammasome -mediated pyroptosis, and the activation of microglia, which provided a potential target for treating TBI.
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