Investigation of Ferroptosis Mechanisms in Ischemic Stroke Treated with Electroacupuncture: Focusing on the NCOA4-FTH1 Signaling Pathway

Ischemic stroke remains a primary cause of mortality and morbidity, with ferroptosis emerging as a critical mechanism underlying neuronal damage post-ischemic injury. This study aims to elucidate the mechanisms of ferroptosis in ischemic stroke and assess the therapeutic potential of electroacupuncture, with emphasis on the NCOA4-FTH1 signaling pathway. After establishing a mouse model of middle cerebral artery occlusion (MCAO), we employed a combination of behavioral assessments and molecular techniques, including transmission electron microscopy, immunofluorescence, and Western blotting, to investigate the impact of electroacupuncture on ferroptosis markers. In addition, we constructed in vivo models of NCOA4 gene silencing and overexpression using adeno-associated virus (AAV) to verify whether electroacupuncture modulates the mechanism of ischemic stroke ferroptosis via the NCOA4-FTH1 signaling pathway. Our findings indicated that electroacupuncture could significantly downregulate NCOA4 expression while upregulating FTH1 and GPX4 levels in affected brain regions of MCAO mice. This resulted in reduced MDA levels, decreased iron ion concentration, a smaller brain infarct area, and improved motor function (p < 0.05). After constructing in vivo models of AAV-mediated NCOA4 gene silencing and overexpression, we demonstrated that electroacupuncture could attenuate iron deposition and inhibit ferroptosis in neurons by suppressing NCOA4 and upregulating FTH1, thereby ameliorating neurological deficits in the ischemic stroke model. These results suggest that electroacupuncture modulates ferroptosis through the NCOA4-FTH1 pathway, offering a novel therapeutic approach for neuroprotection following ischemic stroke.