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Review | Open Access

Broadening horizons: ferroptosis as a new target for traumatic brain injury

Ziqing Wei1,2,3,†, Haihan Yu1,†, Huijuan Zhao4, Mingze Wei5, Han Xing6,7, Jinyan Pei8, Yang Yang9 ( ), Kaidi Ren6,7 ( )
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, No. 1, Jianshe East Road, Erqi District, Zhengzhou, China
Henan Key Laboratory of Cerebrovascular Diseases, The First Affiliated Hospital of Zhengzhou University, No. 1, Jianshe East Road, Erqi District, Zhengzhou, China
Clinical Systems Biology Laboratories, The First Affiliated Hospital of Zhengzhou University, No. 1, Longhu Middle Ring Road, Jinshui District, Zhengzhou, China
Henan International Joint Laboratory of Thrombosis and Hemostasis, College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, No. 1, Longhu Middle Ring Road, Jinshui District, Luoyang, China
The Second Clinical Medical College, Harbin Medical University, No. 263, Kaiyuan Avenue, Luolong District, Harbin, China
Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, No. 246, Xuefu Road, Nangang District, Zhengzhou 450052, China
Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, No. 1, Jianshe East Road, Erqi District, Zhengzhou 450052, China
Quality Management Department, Henan No.3 Provincial People’s Hospital, No. 198, Funiu Road, Zhongyuan District, Henan province, Zhengzhou 450052, China
Clinical Systems Biology Research Laboratories, Translational Medicine Center, the First Affiliated Hospital of Zhengzhou University, No. 198, Funiu Road, Zhongyuan District, Zhengzhou 450052, China

†These authors contributed equally to this work.

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Highlights

• We concluded the role of ferroptosis in TBI, focusing on iron metabolism and lipid metabolism disorder, and the regulatory axis of System Xc-/GSH/GPX4 in TBI.

• We indicated the involvement of ferroptosis in the chronic TBI stage.

• We discussed the potential therapeutic interventions targeting ferroptosis after TBI.

Abstract

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide, with ~50 million people experiencing TBI each year. Ferroptosis, a form of regulated cell death triggered by iron ion-catalyzed and reactive oxygen species-induced lipid peroxidation, has been identified as a potential contributor to traumatic central nervous system conditions, suggesting its involvement in the pathogenesis of TBI. Alterations in iron metabolism play a crucial role in secondary injury following TBI. This study aimed to explore the role of ferroptosis in TBI, focusing on iron metabolism disorders, lipid metabolism disorders and the regulatory axis of system Xc−/glutathione/glutathione peroxidase 4 in TBI. Additionally, we examined the involvement of ferroptosis in the chronic TBI stage. Based on these findings, we discuss potential therapeutic interventions targeting ferroptosis after TBI. In conclusion, this review provides novel insights into the pathology of TBI and proposes potential therapeutic targets.

References

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Burns & Trauma
Article number: tkad051

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Cite this article:
Wei Z, Yu H, Zhao H, et al. Broadening horizons: ferroptosis as a new target for traumatic brain injury. Burns & Trauma, 2024, 12: tkad051. https://doi.org/10.1093/burnst/tkad051

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Received: 11 July 2023
Revised: 24 August 2023
Accepted: 15 October 2023
Published: 10 October 2026
© The Author(s) 2024. Published by Oxford University Press.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.