创伤性脑损伤
粒体自噬
神经保护
免疫印迹
神经炎症
活力测定
医学
药理学
化学
免疫学
自噬
精神科
炎症
细胞凋亡
生物化学
基因
作者
Fan Wu,Tao Liang,Yang Liu,Yongxing Sun,Baoguo Wang
标识
DOI:10.1016/j.expneurol.2024.114876
摘要
Hydrogen (H2) has emerged as a potential therapeutic intervention for traumatic brain injury (TBI). However, the precise mechanism underlying H2's neuroprotective effects in TBI remain incompletely understood. TBI mouse model was induced using the controlled cortical impact (CCI) method, and a cell model was established by exposing astrocytes to lipopolysaccharide (LPS). Cell viability was detected by CCK-8 kits. Cell apoptosis was measured by flow cytometry. ELISA was used to detect cytokine quantification. Protein and gene expression was detected by western blot and RT-PCR analysis. Co-immunoprecipitation (CO-IP) were employed for protein-protein interactions. Morris water maze test and rotarod test were applied for TBI mice. H2 treatment effectively inhibited the LPS-induced cell injury and cell apoptosis in astrocytes. NEDD4 expression was increased following HRS treatment coupled with enhanced mitophagy in LPS-treated astrocytes. Overexpression of NEDD4 and down-regulation of connexin 43 (CX43) mirrored the protective effects of H2 treatment in LPS-exposed astrocytes. NEDD4 interacts CX43 to regulates the ubiquitinated degradation of CX43. While overexpression of CX43 reversed the protective effects of H2 treatment in LPS-exposed astrocytes. In addition, H2 treatment significantly alleviated brain injury in TBI mouse model. H2 promoted NEDD4-CX43 mediated mitophagy to protect brain injury induced by TBI, highlighting a novel pathway underlying the therapeutic effects of H2 in TBI.
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