Targeting ferroptosis by electroacupuncture offers a therapeutic regimen for brain injury after ischemic stroke

Abstract

Ischemic stroke (IS), the most prevalent form of stroke, remains a significant healthcare challenge and imposes a considerable burden on affected individuals. Ferroptosis, a form of regulated cell death (RCD) characterized by iron overload -induced lipid peroxidation, was identified as a contributor to induce cell death following brain injury after ischemic stroke. Targeting ferroptosis is a novel therapy regimen for IS. And seeking novel therapy is unmet need for IS. Electroacupuncture (EA) has been revealed to have neuroprotective effect against IS and recommended to treat IS by World Health Organization (WHO) for years, but the specific mechanism underlying EA-mediated neuroprotection is still elusive. Emerging evidences have shown that EA alleviates brain injury after ischemic stroke by inhibiting ferroptosis; however, the mechanism by which EA suppresses ferroptosis against IS has not been sufficiently clarified. In this review, we first summarizes the core molecular mechanism of ferroptosis, with an focus on interpret how ferroptosis leads to the genesis of brain injury after ischemic stroke and the novel regulation of ferroptosis during the brain injury after ischemic stroke. We then highlights our emphasize on the emerging evidences that have revealed EA inhibit ferroptosis and review their pharmacological mechanisms against brain injury after ischemic stroke. This review highlights EA as a novel therapeutic regimen for ischemic stroke by suppressing ferroptosis, synthesizing mechanistic insights into iron-dependent lipid peroxidation pathways, evaluating emerging experimental evidence of EA's neuroprotection, and proposing targeted clinical strategies to mitigate post-stroke brain injury.