Fenofibrate alleviates the brain edema after traumatic brain injury by enhancing endothelial OXPHOS

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.

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Publication Details

Journal
Redox Biology
Published
2026-05-27
DOI
https://doi.org/10.1016/j.redox.2026.104240
Primary Topic
Traumatic Brain Injury and Neurovascular Disturbances
Type
article
Field-Weighted Citation Impact
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article

Fenofibrate alleviates the brain edema after traumatic brain injury by enhancing endothelial OXPHOS

Weiji Weng, Galbadrakh Erdenetsetseg, Junfeng Feng, Wenye Wang et al.
Redox Biology
Traumatic Brain Injury and Neurovascular Disturbances
article

Fenofibrate alleviates the brain edema after traumatic brain injury by enhancing endothelial OXPHOS

Weiji Weng, Galbadrakh Erdenetsetseg, Junfeng Feng, Wenye Wang, Yuhan Han, Yingwei Gao, Zhifan Li, Wenlan Qi, Jialin Huang, Jiyuan Hui, Zixuan Ma, Zhenghui He, Daiwen Zhang, Qing Mao, Yan Zhang, Yong Lin, Yan Zhou, Qiyuan Feng, Jiyao Jiang, Xinxin Zhao, Xiaokun Gu, Jian Zhang, Bayasgalan Onondari, Xinwen Liu
article en

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.

Redox BiologyVol. 94
Nanchang University (CN), Shanghai Jiao Tong University (CN), Renji Hospital (CN), Mongolian National University (MN), Jiangxi Provincial Academy of Medical Sciences (CN), First Affiliated Hospital of Jiangxi Medical College (CN), Shanghai Fire Research Institute (CN), Second Affiliated Hospital of Nanchang University (CN), National University of Mongolia (MN)
Openalex Percentile: Top 6%
Traumatic Brain Injury and Neurovascular Disturbances
DOIOpen Access PDFOpenAlex
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