Ferroptosis and Its Crosstalk with Other Cell Death Modes in Ischemic Stroke

Ischemic stroke is the most common cerebrovascular disease. The core pathological mechanism underlying its neurological deficits is the massive neuronal death triggered by cerebral ischemia, hypoxia, and reperfusion injury following a sudden interruption of cerebral blood flow. Ferroptosis is a form of cell death characterized by iron overload, amino acid metabolism disorder, and lipid peroxidation, primarily occurring during organ ischemia-reperfusion. In recent years, with the clinical advancement of intravenous thrombolysis and endovascular thrombectomy, the incidence of ferroptosis in neurons after ischemic stroke has increased significantly. Importantly, substantial evidence indicates that ferroptosis not only directly damages neurons but also acts synergistically with other modes of cell death, further exacerbating brain tissue injury. Therefore, this review summarizes the mechanisms of ferroptosis following ischemic stroke, its role in neurological impairment, and explores the synergistic interactions between ferroptosis and other cell death pathways, which will provide an important theoretical foundation for the development of neuroprotective pharmacological therapies and innovative treatment strategies for ischemic stroke.