Acupuncture alleviates brain injury by inhibiting neuroinflammation after acute cerebral infarction, 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.
Key Findings
Results
SPP1 (Secreted Phosphoprotein 1) was identified as a differentially expressed protein elevated in ACI patients compared to healthy controls.
Serum from ACI patients and healthy controls was analyzed using four-dimensional data-independent acquisition (4D-DIA)-based proteomics to identify differentially expressed proteins (DEPs).
SPP1 was validated as a candidate DEP using enzyme-linked immunosorbent assay (ELISA).
Correlation analyses were performed to assess the relationship between SPP1 levels and clinical parameters.
Results
Acupuncture downregulated elevated SPP1 levels in both MCAO rats and ACI patients.
SPP1 expression was elevated following acute cerebral infarction in both the clinical and animal model settings.
Acupuncture treatment reduced SPP1 levels in a rat model of ACI subjected to permanent occlusion of the middle cerebral artery (MCAO).
The reduction in SPP1 was observed concurrently with improvements in neurological outcomes.
Results
Acupuncture substantially improved neurological function, reduced infarction volume, and alleviated neuronal damage in MCAO rats.
Neurological outcomes were assessed in a rat model using permanent middle cerebral artery occlusion (MCAO).
Infarction volume was measured using triphenyltetrazolium chloride (TTC) staining.
Neuronal damage was assessed via Nissl staining and immunofluorescence staining.
Acupuncture treatment showed substantial improvements across all morphological and functional measures compared to untreated MCAO controls.
Results
Acupuncture promoted polarization of microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype.
Microglial polarization was assessed via immunofluorescence staining, western blot assays, and real-time quantitative PCR.
Pro-inflammatory cytokines IL-6, IL-1β, and TNF-α were reduced following acupuncture treatment.
Anti-inflammatory markers Arg-1, IL-10, and TGF-β1 were increased following acupuncture treatment.
Microglia serve as key initial responders in neuroinflammation following ACI, making their polarization state a critical determinant of disease outcome.
Results
Acupuncture may modulate the CD200/CD200R signaling pathway through reduction of SPP1 expression.
The CD200/CD200R pathway is implicated in regulating microglial activation and immune homeostasis in the brain.
Acupuncture-induced downregulation of SPP1 was associated with modulation of CD200/CD200R pathway activity.
This pathway modulation is proposed as a mechanism by which acupuncture may restore immune homeostasis in the ischemic brain.
Western blot assays and real-time quantitative PCR were among the methods used to assess molecular biological alterations.
What This Means
This research suggests that acupuncture can reduce harmful brain inflammation after a stroke (acute cerebral infarction) by targeting a specific protein called SPP1 (Secreted Phosphoprotein 1). The researchers found that SPP1 levels were abnormally high in the blood of stroke patients and in rats with experimentally induced strokes. When acupuncture was applied to the rats, SPP1 levels dropped, and the animals showed less brain damage, smaller areas of dead tissue, and better neurological function. The study used a combination of advanced protein analysis techniques and laboratory assays to trace these effects from human patients down to the molecular level in animals.
A key finding was that acupuncture appeared to shift the behavior of microglia — the brain's resident immune cells — from an aggressive, inflammation-promoting state (called M1) to a protective, inflammation-resolving state (called M2). This shift was reflected in lower levels of pro-inflammatory molecules like IL-6, IL-1β, and TNF-α, and higher levels of anti-inflammatory molecules like IL-10 and TGF-β1. The researchers also found evidence that acupuncture may work in part by activating a molecular communication system called the CD200/CD200R pathway, which normally helps keep the brain's immune response in check.
This research suggests that acupuncture may have a specific, identifiable molecular mechanism for reducing post-stroke brain inflammation, rather than acting in a vague or non-specific way. By identifying SPP1 and the CD200/CD200R pathway as potential targets, the study opens possible avenues for understanding how acupuncture interacts with the brain's immune system after injury. However, these findings are based on animal models and proteomic analyses of patient serum, and further clinical research would be needed to confirm whether these mechanisms operate the same way in human stroke treatment.
Cao J, Liu X, Wang L, Zhou Y, Zhang L, Chen X, et al.. (2026). Acupuncture Attenuates Neuroinflammation Following Acute Cerebral Infarction by Downregulating SPP1 to Ameliorate Immunological Niches.. Brain and behavior. https://doi.org/10.1002/brb3.71699