Fenofibrate alleviates the brain edema after traumatic brain injury by enhancing endothelial OXPHOS
Year: 2026
Type: article
Abstract: Traumatic brain injury (TBI) frequently leads to brain edema, a life-threatening complication and a major cause of mortality and disability. Here, we report that fenofibrate (FFB), an agonist of the nuclear receptor peroxisome proliferator-activated receptor-α (PPARα), alleviates post-traumatic brain edema by enhancing blood-brain barrier (BBB) integrity in a mouse model of severe TBI. Mechanistic studies in cultured endothelial cells and endothelial-specific PPARα conditional knockout mice revealed that FFB activates PPARα, enhances mitochondrial oxidative phosphorylation (OXPHOS), and thereby reduces oxidative stress and endothelial cell apoptosis. These findings identify PPARα-dependent enhancement of energy metabolism in the brain endothelium as a promising therapeutic strategy for TBI-induced edema.
Source: Redox Biology
Authors: Qiyuan Feng, Yingwei Gao, Xiaokun Gu, Xinxin Zhao, Xinwen Liu, Zixuan Ma, Wenlan Qi, Zhenghui He, Yuhan Han, Jian Zhang, Wenye Wang, Zhifan Li, Daiwen Zhang, Jialin Huang, Yong Lin, Jiyuan Hui, Bayasgalan Onondari, Galbadrakh Erdenetsetseg, Qing Mao, Jiyao Jiang, Yan Zhou, Weiji Weng, Yan Zhang, Junfeng Feng
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,310
OpenAlex ID: W7162560871