Cerebroprotective Effect of Acupuncture on Ischemic Stroke by Inhibiting Ferroptosis via the SLC7A11/GPX4 Pathway

Objective Clinical studies have shown that acupuncture can promote functional recovery after ischemic stroke. This study aimed to evaluate the neuroprotective effects of manual acupuncture in a rat model of ischemic stroke and to investigate whether these effects are associated with ferroptosis and changes in the SLC7A11/GPX4 axis. Methods A middle cerebral artery occlusion (MCAO) model was established in rats. The neuroprotective effects of manual acupuncture were evaluated using the modified Neurological Severity Score (mNSS) and 2,3,5-triphenyltetrazolium chloride (TTC) staining. Mitochondrial ultrastructure was examined by transmission electron microscopy. Iron deposition was assessed by Prussian blue staining, and glutathione peroxidase 4 (GPX4) expression was analyzed by immunofluorescence. Biochemical assays were used to measure ferroptosis-related biomarkers, including iron, glutathione (GSH), and malondialdehyde (MDA). Western blot analysis was performed to assess the expression of solute carrier family 7 member 11 (SLC7A11) and GPX4. Results Ferroptosis-related changes were observed in ischemic brain regions of MCAO rats. Manual acupuncture significantly improved neurological outcomes, reduced cerebral infarct volume, and modulated ferroptosis-related markers (↓MDA, ↓iron deposition; ↑GSH, ↑GPX4/SLC7A11). These effects were enhanced by co-treatment with the ferroptosis inhibitor desferrioxamine (DFO) and attenuated by co-treatment with the ferroptosis inducer imidazole ketone erastin (IKE), supporting the involvement of ferroptosis-related mechanisms in acupuncture-mediated neuroprotection. Conclusion This study suggests that manual acupuncture exerts neuroprotective effects in MCAO rats and is associated with reduced ferroptosis-related injury, with increased SLC7A11 and GPX4 expression.