Precision medicine targeting ferroptosis in cerebrovascular diseases

Ferroptosis has emerged as a critical contributor to secondary brain injury in cerebrovascular diseases (CVDs). However, the clinical translation of antiferroptotic therapies remains stalled because current strategies often treat CVDs as a uniform entity, neglecting profound pathophysiological heterogeneity. In this review, we propose a pathology-guided framework mapping distinct ferroptotic cascades across CVDs. We delineate how ischemic stroke hinges on endogenous iron retention and the collapse of nuclear factor erythroid 2-related factor 2 antioxidant defenses, whereas hemorrhagic stroke is triggered by acute exogenous heme influx. Furthermore, chronic hypoperfusion in vascular dementia lowers the threshold for oligodendrocyte ferroptosis. By deconstructing these subtype-specific mechanisms-from iron overload modes to lipid vulnerability-we emphasize a paradigm shift for CVD: advancing precision medicine requires mechanism-stratified, context-dependent interventions rather than uniform ferroptosis inhibition.