Ferroptosis in Neurovascular Unit of Ischemic Stroke: Multidimensional Regulatory Mechanisms and Targeted Interventions

Ischemic stroke ranks among the leading global causes of death and disability, driven by intricate mechanisms such as neuronal injury, inflammation, and oxidative stress. Emerging as a pivotal player in ischemic stroke progression is ferroptosis—an iron-dependent form of regulated cell death. Its hallmarks—iron metabolic dysregulation and lipid peroxidation—trigger cell membrane disruption and irreversible neuronal damage. Beyond that, ferroptosis intensifies inflammation and compromises the blood–brain barrier (BBB), substantially increasing the impact of ischemic injury. Research indicates that modulating ferroptosis-related molecular pathways could significantly mitigate the pathological progression of ischemic stroke. Based on a systematic search of PubMed, Web of Science, Embase, and Cochrane Library databases (as of April 30, 2025), this review focuses on the progress of research on the mechanisms and treatments of ferroptosis in ischemic stroke over the past five years, aiming to investigate the underlying mechanisms, pathological roles, cross-disease associations, and targeted therapeutic strategies, to lay a theoretical foundation for the development of advanced therapies, and to outline the challenges and future directions of the field.