Electroacupuncture Attenuates Cerebral Ischemia–Reperfusion Injury via Vagus Nerve–α7 Nicotinic Acetylcholine Receptor–Dependent Microglial Polarization

BACKGROUND: Neuroinflammation is a central pathological process in cerebral ischemia/reperfusion injury. Electroacupuncture has demonstrated neuroprotective potential in ischemic stroke; however, whether electroacupuncture engages a defined central cholinergic anti-inflammatory reflex to regulate microglial phenotype remains unknown. METHODS: A rat model of middle cerebral artery occlusion/reperfusion was employed. Low-intensity electroacupuncture was applied to the acupoints Large Iintestine 10 and Stomach 36 immediately after reperfusion. Neurological deficits and structural damage were assessed using neurological behavioral scores, 2,3,5-triphenyltetrazolium chloride staining, and hematoxylin and eosin staining. Western blot, immunofluorescence, quantitative real-time polymerase chain reaction, and ELISA were used to evaluate α7nAChR (α7 nicotinic acetylcholine receptor) expression, microglial phenotypic markers, and TLR4/NF-κB (toll-like receptor 4/nuclear factor kappa B) pathway activity. Functional validation was performed using the α7nAChR antagonist α-BGT (α-bungarotoxin) and subdiaphragmatic vagotomy. RESULTS: Electroacupuncture intervention significantly improved neurological function scores, reduced infarct volumes in middle cerebral artery occlusion/reperfusion rats. Electroacupuncture upregulated α7nAChR expression in the ischemic penumbra, primarily localized to microglia, and this effect was abolished by vagotomy. Eelectroacupuncture suppressed the TLR4/MyD88 (myeloid differentiation primary response 88)/NF-κB signaling pathway in an α7nAChR-dependent manner and shifted microglial polarization from a proinflammatory phenotype toward an anti-inflammatory phenotype. These effects were reversed by α-BGT and subdiaphragmatic vagotomy. CONCLUSIONS: This study elucidates that low-intensity electroacupuncture alleviates neuroinflammation following cerebral ischemia/reperfusion injury by activating the vagus nerve-α7nAChR axis, which negatively regulates the TLR4/NF-κB pathway and drives microglial polarization toward an anti-inflammatory phenotype. These findings identify the vagus nerve-α7nAChR axis as a critical neuroimmune pathway underlying electroacupuncture-mediated neuroprotection and suggest that targeted neuromodulation of this axis may represent a promising adjunctive strategy for ischemic stroke therapy.