Electroacupuncture attenuates cerebral ischemia-reperfusion injury.

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

Jing-Yuan Niu, Xin Luo, Xian-Dong Li, Jian Zhang, Qiong Wu, Yi-Feng Pei, Jia-Qi Wang, Qian-Kun Zhao, Yue Wang, Gong Zhang, Hui-Sheng Chen

J Am Heart Assoc

Jul 6, 2026

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Abstract

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 evaluateα7nAChR (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 theα7nAChR antagonistα-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 upregulatedα7nAChR 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 anα7nAChR-dependent manner and shifted microglial polarization from a proinflammatory phenotype toward an anti-inflammatory phenotype. These effects were reversed byα-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.