SYSTEMATIC REVIEW article
Front. Neurol.
Sec. Experimental Therapeutics
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1648117
Acupuncture Improve Blood-Brain Barrier Integrity and Multi-Target Mechanisms: A Preclinical Meta-Analysis
Provisionally accepted
- 1针灸康复临床医学院 广州中医药大学, 广州市, China
- 2广州中医药大学, 广州市, China
- 3广州医科大学附属中医医院, 广州市, China
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Objective: The objective of this study is to assess the impact of acupuncture. regarding blood-brain barrier (BBB) permeability and provide a data foundation for clinical practice. Methods: A database search was carried out in PubMed, Embase, Cochrane Library, and Web of Science to collect controlled animal experiments that investigated the impact of acupuncture on BBB permeability. BBB permeability was primarily assessed by indicators such as Evans Blue (EB) extravasation. The SYRCLE risk-of-bias tool was utilized to assess the quality of the comprised studies, and statistical software was employed for data evaluation. For continuous outcomes, a random-effects model was used to calculate pooled standardized mean differences (SMD) with 95% confidence intervals (CI), and heterogeneity was quantified using the I² statistic. Results: Thirty-two papers were incorporated. Outcomes from the meta-analysis showed that acupuncture significantly reduced the EB leakage in brain tissue (SMD = -0.65, 95% CI [-0.94, -0.37], p < 0.001), indicating its effectiveness in improving BBB permeability. Additionally, acupuncture upregulated the levels of occludin, claudin-5, and ZO-1, inhibited the activity of matrix metalloproteinase-9 (MMP-9), reduced the amounts of glial activation markers (Iba-1, GFAP) and inflammatory mediators (IL-1β, IL-6, TNF-α), and regulated the levels of aquaporin-4 (AQP4). Conclusion: acupuncture may improve BBB integrity by means of multiple mechanisms, including the enhancement of tight junction protein production in endothelial cells, inhibiting MMP-9 mediated extracellular matrix (ECM) degradation, modulating glial cell activation and inflammatory responses, and downregulating AQP4-dependent edema.
Keywords: Acupuncture, blood-brain, Barrier, Permeability, Meta-analysis, Systematic review
Received: 18 Jun 2025; Accepted: 13 Oct 2025.
Copyright: © 2025 Zhang, Liang, Wang, Yin and Ming. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Kangwen Ming, mkw1976_medicine@cqu-edu.cn
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.