Ferroptosis in Ischemic Stroke: Animal Models and Mechanisms

Stroke is a major cause of death and disability globally, most of which are ischemic strokes caused by arterial occlusion. At present, the main treatment methods are rapid reperfusion through intravenous thrombolysis and intravascular thrombectomy. Although both can reduce disability, the reperfusion can still cause neuronal injury. The exact mechanism of neuronal damage after cerebral ischemia is yet to be unveiled. The latest research indicated that ferroptosis may be one main form of neuronal death after ischemic stroke, which can be targeted to prevent neuronal loss. This review introduces three essential hallmarks of ferroptosis: the availability of redox-active iron, oxidation of polyunsaturated fatty acid (PUFA)-containing phospholipids, and the loss of lipid peroxide repair capacity, and reviews the mechanism of ferroptosis involved in neuronal injury after ischemic stroke. It also summarizes the alterations in ferroptosis in different types of ischemic stroke animal models and introduces newly discovered interventions targeting the ferroptosis pathway. Finally, the opportunities, difficulties, and future directions of ferroptosis targeting in ischemic stroke were discussed.