In recent years, the morbidity, mortality and disability of stroke have been increasing in most countries, with ischemic stroke accounting for 62.4% of all incident strokes (Collaborators, 2021). Ischemic stroke is a disease in which the stenosis or occlusion of brain feeding artery leads to insufficient blood supply to the brain, resulting in the necrosis of brain tissue. Long-term cerebral ischemia can cause irreversible neuronal damage and neurological dysfunction, severely affecting the quality of life of patients and placing a heavy burden on families and society. At present, reperfusion therapy with drugs or surgery is still the main effective treatment. The key to this neuroprotective therapy is to save the ischemic penumbra around the necrotic core where blood supply is less reduced. It is hoped that brain injury at ischemic penumbra may be saved by early reperfusion therapy. However, if brain tissue remains ischemic for an extended period of time, the necrotic core region will expand, leading to irreversible neuronal damage at the periphery. Limited time window, together with the low recanalization rate and large number of thrombolytic contraindications (Tuo et al., 2022b), limits the clinical benefits of reperfusion therapy.

Recent studies have shown that ferroptosis is associated with the occurrence and development of cancer, neurodegeneration, ischemia reperfusion injury and other diseases (Jiang et al., 2021). Therefore, a thorough understanding of the role of ferroptosis in ischemic stroke could help to provide new intervention targets for ischemic stroke. Ferroptosis, firstly proposed by Dixon et al. in 2012, is a new type of regulated cell death characterized by iron accumulation and lipid peroxidation (Dixon et al., 2012). In terms of cell morphology, ferroptosis is mainly manifested as follows: plasma membrane blistering and rupture, smaller mitochondria, increased membrane density, mitochondrial cristae reduction, and mitochondrial outer membrane rupture, with a normal sized nucleus and no chromatin condensation (Sepand et al., 2021).

This review will summarize the molecular mechanisms of ferroptosis and the pathways to resist ferroptosis (Fig. 1) and then review the mechanisms of ferroptosis in ischemic stroke (Fig. 2) ,and then present the latest findings on targeted ferroptosis therapy for ischemic stroke (Table 1, Table 2, Table 3).