Abstract
Background: Vascular dementia (VD), primarily caused by cerebral hypoperfusion, is a major dementia subtype. Our previous studies demonstrated that acupuncture improves clinical outcomes in VD patients and modulates their peripheral immune responses. Nevertheless, the mechanistic interplay between acupuncture-mediated peripheral immunomodulation and cognitive enhancement remains to be elucidated. Methods: The cognitive abilities of rats were assessed using the Morris water maze (MWM), novel place recognition (NPR), and novel object recognition (NOR) tests. Neuronal injury and apoptosis in the hippocampal CA1 and CA3 regions were evaluated by hematoxylin and eosin (HE) staining and TUNEL assay. Immunofluorescence staining was performed to detect microglial activation markers (Iba-1 and CD68). Cytokine levels-including interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), IL-2, IL-17A, IL-4, IL-10, transforming growth factor-β (TGF-β), and IL-35-in hippocampal tissues and peripheral blood were quantified by enzyme-linked immunosorbent assay (ELISA). Western blotting was employed to analyze the expression of cleaved-caspase 3, caspase-3, Bcl-2, and Bax in rat hippocampal tissues. Flow cytometry was used to analyze the proportion, proliferation, and apoptosis of CD3⁺ T cells, CD4⁺ T cells, and CD8⁺ T cells in peripheral blood. Results: Acupuncture ameliorated cognitive impairment in VD rats, reduced hippocampal neuronal damage and apoptosis, downregulated pro-apoptotic proteins (cleaved-caspase 3 and Bax), and upregulated anti-apoptotic Bcl-2. Furthermore, it suppressed microglial activation markers (Iba-1 and CD68), decreased pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-2, IL-17A), and elevated anti-inflammatory cytokines (IL-4, IL-10, TGF-β, IL-35) in the brain. Simultaneously, acupuncture modulated peripheral inflammatory cytokine profiles, increased CD3⁺ T cell and CD4⁺ T cell proportions, and reduced T-cell apoptosis in peripheral blood of VD rats. Conclusions: Acupuncture improved cognitive impairment in VD rats and suppressed neuroinflammation and neuronal apoptosis; these benefits may be mediated, at least partially, through modulation of peripheral immunity.