Electroacupuncture pretreatment alleviates cerebral Ischemia-Reperfusion-Induced intestinal barrier injury and neuroinflammation via inhibition of the TLR4/NLRP3 inflammasome pathway in rats

Sep 12, 2025Brain research

Electroacupuncture before stroke reduces intestinal damage and brain inflammation by blocking a key immune pathway in rats

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Abstract

Electroacupuncture pretreatment significantly reduced intestinal mucosal edema and inflammatory infiltration following cerebral ischemia-reperfusion injury.

Electroacupuncture pretreatment improved neurological deficits after cerebral ischemia-reperfusion injury.
It suppressed the TLR4/NF-κB/NLRP3 inflammasome pathway, leading to decreased levels of pro-inflammatory cytokines.
EA pretreatment increased anti-inflammatory factors and the antioxidant protein TRX1.
Plasma levels of lipopolysaccharide, diamine oxidase, and D-lactate were lowered, indicating restored intestinal barrier function.
Gut microbiota analysis showed that EA pretreatment inhibited pathogenic bacteria and rebalanced the Firmicutes/Bacteroidetes ratio.

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This study investigates the protective effects and mechanisms of electroacupuncture (EA) pretreatment on intestinal barrier dysfunction following cerebral ischemia-reperfusion injury (CIRI), with a focus on the TLR4/NLRP3 inflammasome pathway. A middle cerebral artery occlusion (MCAO) rat model was established, with groups divided into Sham, ischemia-reperfusion (I/R), and EA pretreatment (I/R + EA). Neurological function and intestinal pathology were dynamically assessed at 2, 24, and 72 h post-reperfusion. Results demonstrated that EA pretreatment significantly attenuated CIRI-induced intestinal mucosal edema, inflammatory infiltration, and fibrosis, while improving neurological deficits. Mechanistically, EA pretreatment suppressed the TLR4/NF-κB/NLRP3 inflammasome axis, reducing pro-inflammatory cytokines (IL-1β, IL-18) and enhancing anti-inflammatory factors (TGF-β1, IL-4) and the antioxidant protein TRX1. Concurrently, it lowered plasma levels of lipopolysaccharide (LPS), diamine oxidase (DAO), and D-lactate, restoring intestinal epithelial tight junctions. 16S rDNA sequencing revealed that EA pretreatment reversed CIRI-induced gut microbiota dysbiosis, inhibiting pathogenic Escherichia-Shigella proliferation and rebalancing the Firmicutes/Bacteroidetes ratio. This study firstly identifies that EA pretreatment establishes a "neuro-immune-microbial" protective network through spatiotemporal modulation of the TLR4/NLRP3 pathway and microbiota interactions, providing a novel theoretical foundation for the "brain-gut co-protection" strategy in ischemic stroke therapy.

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Electroacupuncture pretreatment alleviates cerebral Ischemia-Reperfusion-Induced intestinal barrier injury and neuroinflammation via inhibition of the TLR4/NLRP3 inflammasome pathway in rats

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