Electroacupuncture Attenuates Cerebral Ischemia/Reperfusion Injury and Enhances Neurological Recovery via Modulating Ferroptosis-Associated Proteins

Abstract

Objective: This study aimed to investigate the effects of electroacupuncture (EA) on cerebral ischemia-reperfusion injury (CIRI), neurological function, and regulatory effects on the expression of ferroptosis-associated proteins in rats. Methods: Thirty-six 3-month-old male Sprague Dawley rats were randomly assigned to sham, CIRI model (model), and CIRI + EA (EA) groups (n = 12 / group). The CIRI model was induced by left middle cerebral artery occlusion. The EA group received daily EA stimulation at GV26/GV20 (3/15 Hz, 1 mA, 20 min) for 5 days, while the sham group underwent sham treatment. Neurological function (Longa score), serum cytokine levels (ELISA), infarct volume (TTC staining), histopathology (H&E and Nissl staining), and protein/mRNA expression (RT-qPCR/Western blot) were evaluated across the groups. Results: ELISA revealed that EA therapy significantly attenuated serum levels of TNF-α and IL-6 in CIRI rats. Compared with the model group, the EA intervention substantially improved limb motor function and decreased Longa scores in the EA group. TTC, H&E staining, and Nissl staining demonstrated that EA therapy significantly attenuated the cerebral infarction volume percentage and mitigated cortical neuronal damage in CIRI rats. Following EA treatment, the EA group exhibited significantly upregulated GPX4 mRNA and protein expressions in the cerebral cortex compared to the model group, while ACSL4 and TFRC expression levels were significantly downregulated. Conclusion: EA treatment effectively alleviates cerebral tissue damage, attenuates inflammatory responses, and improves neurological function in CIRI model rats. The neuroprotective mechanism may be mediated by regulating oxidative stress, enhancing cellular antioxidant capacity, and modulating ferroptosis-associated proteins (ACSL4, GPX4, and TFRC) in the cerebral cortex.