Electroacupuncture at Neiguan (PC6) and Shuigou (GV26) regulates microglial polarization and neuroinflammation through the cGAS-STING signaling pathway in ischemic stroke.

The "Xingnao Kaiqiao" method is an acupuncture approach primarily applied at the PC6 and GV26 acupoints for ischemic stroke (IS). Whether Electroacupuncture (EA) at these acupoints influences the cGAS-STING signaling pathway, affects microglial polarization, and reduces neuroinflammation in IS was the aim of this study. Adult male Sprague-Dawley rats were randomly assigned to five groups: sham, middle cerebral artery occlusion (MCAO), MCAO + EA, MCAO + RU.521, and MCAO + EA + cGAMP. Neurological function scoring, 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, Nissl staining, Masson staining, flow cytometry, enzyme-linked immunosorbent assay (ELISA), RT-qPCR, and Western blotting were conducted for comprehensive evaluation. The MCAO group showed significant neurological impairments, widespread brain damage, and showed elevated pro-inflammatory cytokine levels relative to sham controls. These pathological alterations were substantially reversed by EA treatment. EA administered at the PC6 and GV26 acupoints suppresses excessive activation of the cGAS-STING signaling cascade, thereby decreasing the production of pro-inflammatory mediators while enhancing anti-inflammatory responses. This modulation further facilitates the shift of microglia (MG) from a pro-inflammatory M1 state toward a reparative M2 phenotype. These changes collectively alleviate neuroinflammation and mitigate brain injury.