Ferroptosis Targeting Offers a Therapeutic Strategy for Subarachnoid Hemorrhage

Aneurysmal Subarachnoid Hemorrhage (SAH) is a devastating cerebrovascular event with high morbidity and mortality rates, and early brain injury following SAH (EBI-SAH) within 72 h leads to a poor prognosis. Despite advances in our understanding of the pathogenesis of EBI-SAH, effective therapeutic strategies remain elusive. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation and failure of antioxidant defense, has emerged as a key contributor to neuronal damage in EBI-SAH. This review aims to synthesize knowledge regarding the core molecular mechanisms of ferroptosis, focusing on its role in EBI-SAH initiation and regulation, and comprehensively evaluate diverse pharmacological agents that inhibit ferroptosis to mitigate EBISAH. Natural products (e.g., dihydroquercetin and ginsenoside Rd), synthetic ferroptosis inhibitors (e.g., ferrostatin-1 and deferoxamine), nanomedicines, and small molecules (e.g., melatonin and semaglutide) exert neuroprotective effects by targeting ferroptosis pathways, including the glutathione (GSH)-glutathione peroxidase 4 (GPX4) axis, Nrf2 signaling, iron chelation, and lipid peroxidation suppression. The findings of this study underscore the therapeutic potential of ferroptosis inhibition as a novel strategy to ameliorate EBI-SAH and provide a foundation for future translational research.