Broadening Horizons: Ferroptosis As a New Target for Traumatic Brain Injury

Overview

Journal Burns Trauma

Publisher Oxford University Press

Date 2024 Jan 22

PMID 38250705

Authors

Ziqing Wei

Haihan Yu

Huijuan Zhao

Mingze Wei

Han Xing

Jinyan Pei

Yang Yang

Kaidi Ren

Affiliations

Soon will be listed here.

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.

Citing Articles

Mitigating Remote Organ-Induced Brain Injury in Renal Ischemia-Reperfusion: The Role of Oleuropein in Inhibiting Oxidative Stress, Inflammation, Ferroptosis, and Apoptosis in Male Rats.

Ghaffarinasab M, Kaeidi A, Hassanshahi J J Neuroimmune Pharmacol. 2025; 20(1):24.

PMID: 40056289 DOI: 10.1007/s11481-025-10184-8.

Trehalose Inhibits ferroptosis Through Activating SIRT3/SOD2 Signaling Axis and Alleviates Brain Injury After Traumatic Brain Injury.

Mu Z, Sun Z, Wu S, Yang J, Wang P, Zhao X Neurochem Res. 2025; 50(1):78.

PMID: 39798057 DOI: 10.1007/s11064-024-04330-6.

Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects.

Ru Q, Li Y, Chen L, Wu Y, Min J, Wang F Signal Transduct Target Ther. 2024; 9(1):271.

PMID: 39396974 PMC: 11486532. DOI: 10.1038/s41392-024-01969-z.

References

Yang W, Stockwell B . Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells. Chem Biol. 2008; 15(3):234-45. PMC: 2683762. DOI: 10.1016/j.chembiol.2008.02.010. View

Atif H, Hicks S . A Review of MicroRNA Biomarkers in Traumatic Brain Injury. J Exp Neurosci. 2019; 13:1179069519832286. PMC: 6410383. DOI: 10.1177/1179069519832286. View

Kuang F, Liu J, Li C, Kang R, Tang D . Cathepsin B is a mediator of organelle-specific initiation of ferroptosis. Biochem Biophys Res Commun. 2020; 533(4):1464-1469. DOI: 10.1016/j.bbrc.2020.10.035. View

Cadenas S . ROS and redox signaling in myocardial ischemia-reperfusion injury and cardioprotection. Free Radic Biol Med. 2018; 117:76-89. DOI: 10.1016/j.freeradbiomed.2018.01.024. View

Mueller S, Trabesinger A, Boesiger P, Wieser H . Brain glutathione levels in patients with epilepsy measured by in vivo (1)H-MRS. Neurology. 2001; 57(8):1422-7. DOI: 10.1212/wnl.57.8.1422. View

Rungta R, Choi H, Tyson J, Malik A, Dissing-Olesen L, Lin P . The cellular mechanisms of neuronal swelling underlying cytotoxic edema. Cell. 2015; 161(3):610-621. DOI: 10.1016/j.cell.2015.03.029. View

Miotto G, Rossetto M, Di Paolo M, Orian L, Venerando R, Roveri A . Insight into the mechanism of ferroptosis inhibition by ferrostatin-1. Redox Biol. 2019; 28:101328. PMC: 6812032. DOI: 10.1016/j.redox.2019.101328. View

Alim I, Caulfield J, Chen Y, Swarup V, Geschwind D, Ivanova E . Selenium Drives a Transcriptional Adaptive Program to Block Ferroptosis and Treat Stroke. Cell. 2019; 177(5):1262-1279.e25. DOI: 10.1016/j.cell.2019.03.032. View

Papadopoulos M, Binder D, Verkman A . Enhanced macromolecular diffusion in brain extracellular space in mouse models of vasogenic edema measured by cortical surface photobleaching. FASEB J. 2004; 19(3):425-7. DOI: 10.1096/fj.04-2834fje. View

10.

Zhang Y, Swanda R, Nie L, Liu X, Wang C, Lee H . mTORC1 couples cyst(e)ine availability with GPX4 protein synthesis and ferroptosis regulation. Nat Commun. 2021; 12(1):1589. PMC: 7952727. DOI: 10.1038/s41467-021-21841-w. View

11.

Lee J, Kim W, Bae K, Lee S, Lee E . Lipid Metabolism and Ferroptosis. Biology (Basel). 2021; 10(3). PMC: 8000263. DOI: 10.3390/biology10030184. View

12.

Johnson W, Griswold D . Traumatic brain injury: a global challenge. Lancet Neurol. 2017; 16(12):949-950. DOI: 10.1016/S1474-4422(17)30362-9. View

13.

Mi Y, Gao X, Xu H, Cui Y, Zhang Y, Gou X . The Emerging Roles of Ferroptosis in Huntington's Disease. Neuromolecular Med. 2019; 21(2):110-119. DOI: 10.1007/s12017-018-8518-6. View

14.

Rabinowitz A, Levin H . Cognitive sequelae of traumatic brain injury. Psychiatr Clin North Am. 2014; 37(1):1-11. PMC: 3927143. DOI: 10.1016/j.psc.2013.11.004. View

15.

Yan B, Ai Y, Sun Q, Ma Y, Cao Y, Wang J . Membrane Damage during Ferroptosis Is Caused by Oxidation of Phospholipids Catalyzed by the Oxidoreductases POR and CYB5R1. Mol Cell. 2020; 81(2):355-369.e10. DOI: 10.1016/j.molcel.2020.11.024. View

16.

Movahedpour A, Vakili O, Khalifeh M, Mousavi P, Mahmoodzadeh A, Taheri-Anganeh M . Mammalian target of rapamycin (mTOR) signaling pathway and traumatic brain injury: A novel insight into targeted therapy. Cell Biochem Funct. 2022; 40(3):232-247. DOI: 10.1002/cbf.3692. View

17.

Wang Y, Wei Z, Pan K, Li J, Chen Q . The function and mechanism of ferroptosis in cancer. Apoptosis. 2020; 25(11-12):786-798. DOI: 10.1007/s10495-020-01638-w. View

18.

Blixt J, Svensson M, Gunnarson E, Wanecek M . Aquaporins and blood-brain barrier permeability in early edema development after traumatic brain injury. Brain Res. 2015; 1611:18-28. DOI: 10.1016/j.brainres.2015.03.004. View

19.

Shah S, Kimberly W . Today's Approach to Treating Brain Swelling in the Neuro Intensive Care Unit. Semin Neurol. 2016; 36(6):502-507. PMC: 5319198. DOI: 10.1055/s-0036-1592109. View

20.

Wang W, Bian H, Li F, Li X, Zhang D, Sun S . HBeAg induces the expression of macrophage miR-155 to accelerate liver injury via promoting production of inflammatory cytokines. Cell Mol Life Sci. 2018; 75(14):2627-2641. PMC: 11105519. DOI: 10.1007/s00018-018-2753-8. View