AUTHOR=Zhang Kexing , Liang Ying , Wang Yinxin , Yin Tong , Ming Kangwen 

TITLE=Acupuncture improves blood–brain barrier integrity through multi-targeted mechanisms: a preclinical meta-analysis

JOURNAL=Frontiers in Neurology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1648117

DOI=10.3389/fneur.2025.1648117

ISSN=1664-2295

ABSTRACT=ObjectiveThe 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.MethodsA 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.ResultsThirty-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).Conclusionacupuncture 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.Systematic review registrationhttps://inplasy.com/inplasy-2025-2-0102/, identifier: INPLASY202520102.