Research progress on ferroptosis in cerebral hemorrhage - 20/03/25

Niping Mao ^a,^b,^c,^d,^{^{1
⁎Co-first author}}, Min Zhang ^a,^b,^c,^d,^{^{1
⁎Co-first author}}, Ming Shen ^a,^b,^c,^d, Junhui Yuan ^e,^⁎,^{^{2
Dr. Junhui Yuan is the first corresponding author and Dr. Zhenlang Lin is the second corresponding author.}} , Zhenlang Lin ^a,^b,^c,^d,^⁎,^{^{2
Dr. Junhui Yuan is the first corresponding author and Dr. Zhenlang Lin is the second corresponding author.},}^{^{3
0000-0001-7319-6049}}
^a Department of Neonatology, the Second School of Medicine, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
^b Key Laboratory of Perinatal Medicine of Wenzhou, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
^c Key Laboratory of Structural Malformations in Children of Zhejiang Province, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
^d Zhejiang Provincial Clinical Research Center for Pediatric Disease, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
^e Department of Neonatology, Wenling maternal and child health care hospital, Wenling, Zhejiang, China

^⁎Corresponding author.^⁎⁎Corresponding author at: Department of Neonatology, the Second School of Medicine, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.Department of Neonatology, the Second School of Medicine, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhouZhejiangChina

Abstract

The pathophysiology of intracerebral hemorrhage (ICH) is complex and can cause variable degrees of cell death. Recently, ferroptosis, an emerging cell death mechanism, has garnered significant attention in cerebral hemorrhage disorder. This study aimed to examine iron mortality after cerebral hemorrhage and current targets for potential therapeutic interventions. We specifically focused on iron metabolism abnormalities, lipid peroxidation, and related neuroinflammation and introduced molecular mechanisms, including transcription factors, to gain a better understanding of the underlying mechanisms of ferroptosis and investigate possible therapeutic options for ICH.

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Graphical Abstract

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Highlights

•	Ferroptosis occurs during secondary brain injury after intracerebral hemorrhage.
•	Ferroptosis, a new cell death, occurs in oligodendrocytes, microglia, and neurons.
•	Iron-dependent lipid peroxidation promotes oxidative-antioxidant system imbalance.
•	Transcription factors represented by p53 are essential in ferroptosis regulation.
•	Polarization to M1 microglia produces neuroinflammation and exacerbates brain damage.

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Abbreviations : AA, AdA, Ang II, ARE, BBB, CAMP, CISD1, CO, CREB, DMT1, DPP4, EAAT3, EP, Fer-1, FTL/FTH1, GSH, HCP1, HO-1, HMG1, Hp, Hpx, IL, ICH, IREs, IREB2, IRPs, LCN 2, LIP, LOXs, LPCAT3, LRP1, MDA, MDM, MLKL, NAD, NCOA4, NF-κB, NLRP3, NOX1, Nrf2, PAR, PARP-1, PEB1, PGE2, PKA, PPARs, PUFAs, RIP, ROS, SAT1, SLC7A11, SLC25A28, SOCS, S1P, STAT, Tf, TFR1, TNF