Work

Electroacupuncture Alleviates Brain Injury Through Vagus Nerve Activation and Gut Microbiota in a Rat Model of Ischemic Stroke

Year: 2025

Type: article

Abstract: Background Emerging evidence implicates gut microbiota dysbiosis in exacerbating stroke pathogenesis via the gut‐brain axis, suggesting novel therapeutic targets. While electroacupuncture (EA) demonstrates anti‐inflammatory effects through vagus nerve activation, its neuroprotective mechanisms via vagus nerve–microbiota crosstalk remain unexplored. Methods Rats with middle cerebral artery occlusion received daily ST36 (Acupoint Zusanli) EA for 1 to 7 days postischemia. Subdiaphragmatic vagotomy and fecal microbiota transplant were implemented to validate pathway specificity. Multimodal assessments included longitudinal neurological scoring, infarct volume, systemic/neuroinflammatory profiling (enzyme‐linked immunosorbent assay, immunohistochemistry), intestinal fucosylation dynamics (quantitative polymerase chain reaction, lectin staining), and 16S ribosomal RNA sequencing of gut microbiota. Results EA significantly improved neurological outcomes and reduced infarct volumes at 3 to 7 days after middle cerebral artery occlusion (versus controls), which was abolished by vagotomy. Mechanistically, EA restored gut barrier integrity through vagus‐dependent upregulation of fucosyltransferase 2 (Fut2)‐driven epithelial α1,2‐fucosylation, enhancing mucin 2+ goblet cell density and tight junction protein expression (ZO‐1/occludin/claudin‐1). Concurrent microbiota shifts included Lactobacillales/Bacteroidales enrichment (linear discriminant analysis >4.0) and pathobiont suppression, which was reversed by vagotomy. Crucially, fecal microbiota transplant from EA‐treated donors replicated neuroprotection in germ‐free recipients, achieving 33% infarct reduction and 30% survival improvement ( P =0.012), whereas fecal microbiota transplant from vagotomized donors showed no therapeutic benefits. Conclusions EA at ST36 produced neuroprotection through activating vagal efferent pathways to orchestrate intestinal mucosal repair via Fut2‐mediated fucosylation, which reshape microbial ecosystems and attenuate neuroinflammation. These findings establish a previously unrecognized vagus nerve‐gut‐brain axis mechanism for stroke recovery, positioning microbiota‐directed neuromodulation by EA as a translatable therapeutic strategy.

Source: Journal of the American Heart Association

DOI: 10.1161/jaha.125.045929