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2008 doi: 10.1084/jem.20071412

1 Introduction Stroke remains the second-leading cause of death and disability worldwide, with ischemic stroke accounting for approximately 80% of cases ( First described in 2012, ferroptosis is characterized by mitochondrial cristae shrinkage, glutathione peroxidase 4 (GPX4) inactivation, and lethal lipid peroxide accumulation through iron-dependent Fenton reactions ( Emerging evidence identifies ferroptosis as a maladaptive response in stroke, with its unchecked activation exacerbating infarct volume expansion and worsening functional outcomes ( 2 Mechanisms of ferroptosis Ferroptosis is a distinct form of regulated cell death characterized by the accumulation of lipid peroxides to lethal levels ( The hallmark of ferroptosis lies in the peroxidation of polyunsaturated fatty acids within cellular membranes, driven by an imbalance between ROS and the cells antioxidant defense systems (Figure 1)