# Acupuncture reduces neuroinflammation and apoptosis, regulates peripheral immunity, and modulates T-cell subset distribution in vascular dementia rats

**Authors:** Xinliang Wang, Xiaoxi Liu, Wenyu Zhang, Sai Qi, Jinyan Li, Ruiyu Li, Jingxin Guo, Yifan Zhang, Xuyang Feng, Xuezhu Zhang

PMC · DOI: 10.1186/s13020-025-01243-6 · 2025-11-26

## TL;DR

Acupuncture helps reduce brain inflammation and cell death in rats with vascular dementia, possibly by adjusting immune responses.

## Contribution

This study reveals acupuncture's effects on neuroinflammation, apoptosis, and peripheral immunity in vascular dementia rats.

## Key findings

- Acupuncture reduced hippocampal neuronal damage and apoptosis in VD rats.
- It suppressed microglial activation and pro-inflammatory cytokines in the brain.
- Acupuncture modulated peripheral T-cell subsets and inflammatory cytokine profiles.

## Abstract

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.

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.

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.

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.

The online version contains supplementary material available at 10.1186/s13020-025-01243-6.

## Linked entities

- **Proteins:** AIF1 (allograft inflammatory factor 1), CD68 (CD68 molecule), IL1B (interleukin 1 beta), IL6 (interleukin 6), TNF (tumor necrosis factor), IL2 (interleukin 2), IL17A (interleukin 17A), IL4 (interleukin 4), IL10 (interleukin 10), TGFB1 (transforming growth factor beta 1), Casp3 (caspase 3), BCL2 (BCL2 apoptosis regulator), BAX (BCL2 associated X, apoptosis regulator)
- **Diseases:** vascular dementia (MONDO:0004648)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Il1b (interleukin 1 beta) [NCBI Gene 24494] {aka IL-1F2}, Aif1 (allograft inflammatory factor 1) [NCBI Gene 29427] {aka BART-1, Bart1, iba1, mrf-1}, Casp3 (caspase 3) [NCBI Gene 25402] {aka CPP32-beta, Lice, Yama}, Bax (BCL2 associated X, apoptosis regulator) [NCBI Gene 24887], Cd4 (Cd4 molecule) [NCBI Gene 24932] {aka W3/25, p55}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Bcl2 (BCL2, apoptosis regulator) [NCBI Gene 24224] {aka Bcl-2}, Il17a (interleukin 17A) [NCBI Gene 301289] {aka CTLA-8, IL-17, IL-17A, Il17}, Cd68 (Cd68 molecule) [NCBI Gene 287435], Il2 (interleukin 2) [NCBI Gene 116562], Il10 (interleukin 10) [NCBI Gene 25325] {aka IL10X, If2a}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 59086] {aka Tgfb}, Il4 (interleukin 4) [NCBI Gene 287287] {aka Il4e12}, Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}
- **Diseases:** VD (MESH:D015140), neuroinflammation (MESH:D000090862), inflammatory cytokines (MESH:D000080424), Neuronal injury (MESH:D009410), cognitive impairment (MESH:D003072), cerebral hypoperfusion (MESH:D002547), inflammatory (MESH:D007249), dementia (MESH:D003704)
- **Chemicals:** HE (-)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606]

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12648782/full.md

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Source: https://tomesphere.com/paper/PMC12648782