Acupuncture Attenuates Neuroinflammation Following Acute Cerebral Infarction by Downregulating SPP1 to Ameliorate Immunological Niches.

BACKGROUND: Neuroinflammation following acute cerebral infarction (ACI) critically contributes to disease pathophysiology, with microglia serving as key initial responders. While acupuncture has demonstrated anti-inflammatory and microglia-modulating potential, its molecular mechanisms in reshaping immunological niches remain unclear. METHODS: Serum from ACI patients and healthy controls was analyzed using four-dimensional data-independent acquisition-based proteomics to identify differentially expressed proteins (DEPs). The candidate DEPs were validated using enzyme-linked immunosorbent assay (ELISA), and correlation analyses were performed. We further explored the morphological and molecular biological alterations associated with brain injury and microglial polarization via triphenyltetrazolium chloride (TTC), Nissl, immunofluorescence staining, ELISA, western blot assays, and real-time quantitative PCR in a rat model of ACI subjected to permanent occlusion of the middle cerebral artery (MCAO) with the treatment of acupuncture. RESULTS: Acupuncture downregulated elevated SPP1 levels in both MCAO rats and ACI patients. Concomitantly, it substantially improved neurological function, reduced infarction volume, and alleviated neuronal damage in MCAO rats. Additionally, acupuncture promotes polarization of microglia from the M1 to the M2 phenotype, reducing pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) and increasing anti-inflammatory cytokine (Arg-1, IL-10, and TGF-β1). Furthermore, acupuncture may modulate the CD200/CD200R pathway by reducing SPP1 expression. CONCLUSIONS: Acupuncture alleviates brain injury by inhibiting neuroinflammation after MCAO, an effect that might be mediated through the downregulation of SPP1 and the subsequent modulation of CD200/CD200R signaling, potentially restoring immune homeostasis in the ischemic brain.