1. Academic Validation
  2. HIF-1α aggravated traumatic brain injury by NLRP3 inflammasome-mediated pyroptosis and activation of microglia

HIF-1α aggravated traumatic brain injury by NLRP3 inflammasome-mediated pyroptosis and activation of microglia

  • J Chem Neuroanat. 2021 Oct;116:101994. doi: 10.1016/j.jchemneu.2021.101994.
Dong Yuan 1 ShuangXian Guan 1 Zhen Wang 1 HongLiang Ni 1 DongLiang Ding 1 WenBo Xu 1 GuoMin Li 2
Affiliations

Affiliations

  • 1 Emergency Department, Jintan Hospital Affiliated to Jiangsu University, Changzhou, 213200, Jiangsu, China.
  • 2 Emergency Department, Jintan Hospital Affiliated to Jiangsu University, Changzhou, 213200, Jiangsu, China. Electronic address: xyicu@163.com.
Abstract

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.

Keywords

HIF-1α; Microglia; NLRP3 inflammasome; Pyroptosis; Traumatic brain injury.

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