AUTHOR=Long Zhangling , Zhu Ying , Zhao Heng , Liao Shuang , Liu Cuiying 

TITLE=Ferroptosis in ischemic stroke: mechanisms, pathological implications, and therapeutic strategies

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 19 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2025.1623485

DOI=10.3389/fnins.2025.1623485

ISSN=1662-453X

ABSTRACT=Ferroptosis, an iron-dependent form of cell death driven by lipid peroxidation, has emerged as a pivotal mechanism in the complex pathophysiology of ischemic stroke, a leading cause of global death and disability. This review synthesizes current understanding of the core ferroptosis pathways, including iron dysregulation, glutathione depletion, and GPX4 inactivation and distinguishes it from other cell death modalities. We critically explore its role as a pathogenic amplifier in stroke, synergizing with neuroinflammation and mitochondrial dysfunction to expand neuronal injury. The review systematically assesses therapeutic strategies, from iron chelators and lipid peroxidation inhibitors (e.g., ferrostatin-1) to emerging gene therapies and nanomedicine-based approaches, based on robust preclinical evidence. However, translating these findings faces challenges, including a narrow therapeutic window, patient heterogeneity, and the need to balance efficacy with safety concerning systemic iron and lipid metabolism. To overcome these translational challenges, future research must prioritize the discovery of clinical biomarkers (e.g., FABP5) and the development of targeted delivery systems to advance ferroptosis-directed therapies for stroke.