Abstract
OBJECTIVE: To observe the effect of acupuncture on astrocyte activation following cerebral ischemia-reperfusion injury (CIRI) viathe p38 mitogen-activated protein kinase (p38 MAPK)/mitogen- and stress-activated protein kinase 1 (MSK1) signaling pathway. METHODS: Transcriptome and single-cell sequencing were used to analyse gene expression in middle cerebral artery occlusion (MCAO)-induced rats. Acupuncture was applied at Baihui (GV20) and Dazhui (GV14) for 7 d. The infarct volume was assessed via2,3,5-triphenyltetrazolium chloride staining and T2-weighted imaging. Serum interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha levels were measured viaenzyme-linked immunosorbent assay. The expression of glial fibrillary acidic protein (GFAP), complement component 3 (C3), and S100 calcium-binding protein A10 (S100A10), as well as components of the p38 MAPK/MSK1 pathway, was examined by Western blotting and immunohistochemistry. RESULTS: CIRI activated p38 MAPK signaling, increased the expression of A1 markers (GFAP and C3), and proinflammatory cytokines, and decreased the expression of the A2 marker S100A10. Acupuncture inhibited p38 phosphorylation, upregulated MSK1, reduced C3 and inflammatory cytokines, increased S100A10 expression, decreased infarct volume, and improved neurological function. CONCLUSION: Acupuncture protects against ischemic stroke by targeting the p38 MAPK/MSK1 pathway. It inhibits p38 MAPK phosphorylation and activates MSK1, thereby promoting a shift in astrocyte polarization from the pro-inflammatory A1 to the reparative A2 type, as reflected by decreased C3 and increased S100A10 expression. This shift reduces pro-inflammatory cytokines, alleviates cerebral inflammation, and promotes neural repair, ultimately diminishing infarct volume, restoring neurons, and improving behavior. These findings elucidate the mechanism of acupuncture and support its clinical use.