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Exercise and the blood-brain barrier: Mechanistic insights and therapeutic implications
Zhao-Xin Sun, Fang Xie, Yun Zhao, Xue Wang, Zhao-Wei Sun, Ling-Jia Qian, Hong Feng. Neurobiology of disease, 2025-10-30
Topic: Inflammation, microglia and astrocytes
The blood-brain barrier (BBB) is a critical structure for maintaining homeostasis in the central nervous system, and its dysfunction is widely implicated in the pathogenesis and progression of various neurological disorders. In recent years, exercise, as a low-cost and low-side-effect non-pharmacological intervention, has demonstrated significant potential in modulating the structure and function of the BBB. In this article, we comprehensively review the key mechanisms regulating BBB permeability under physiological and pathological conditions, with a focus on three core pathways: oxidative stress-inflammation-mediated disruption, vascular endothelial growth factor-mediated bidirectional repair, and Wnt/Sonic hedgehog/transcription factor-dependent homeostasis maintenance. Furthermore, we compare the effects of different exercise modalities, including aerobic exercise, high-intensity interval training, and resistance training, on the BBB and discuss their differential impacts across distinct brain regions, populations, and disease states. Additionally, this review integrates rodent and human evidence supporting the therapeutic potential of exercise interventions for patients with typical neurological disorders (e.g., Alzheimer's disease, multiple sclerosis, stroke, and depression) as well as non-disease risk conditions such as obesity and aging that profoundly affect BBB integrity, highlighting its multi-pathway and multi-target mechanisms in maintaining BBB dynamic homeostasis. Overall, the collected evidences support that moderate and regular exercise may protect BBB function through multidimensional mechanisms, offering novel insights and theoretical foundations for non-pharmacological therapies for neurological disorders.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Sun, Z.-X., Xie, F., Zhao, Y., Wang, X., Sun, Z.-W., Qian, L.-J., et al. (2025). Exercise and the blood-brain barrier: Mechanistic insights and therapeutic implications. Neurobiology of disease. https://doi.org/10.1016/j.nbd.2025.107166
Vancouver
Sun Z.-X, Xie F, Zhao Y, Wang X, Sun Z.-W, Qian L.-J, et al. Exercise and the blood-brain barrier: Mechanistic insights and therapeutic implications. Neurobiology of disease. 2025. doi:10.1016/j.nbd.2025.107166. PMID: 41173152.
BibTeX
@article{sun2025-41173152,
author = {Sun, Zhao-Xin and Xie, Fang and Zhao, Yun and Wang, Xue and Sun, Zhao-Wei and Qian, Ling-Jia and Feng, Hong},
title = {{Exercise and the blood-brain barrier: Mechanistic insights and therapeutic implications}},
journal = {Neurobiology of disease},
year = {2025},
doi = {10.1016/j.nbd.2025.107166},
pmid = {41173152},
url = {https://doi.org/10.1016/j.nbd.2025.107166}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- In recent years, exercise, as a low-cost and low-side-effect non-pharmacological intervention, has demonstrated significant potential in modulating the structure and function of the BBB.
- Overall, the collected evidences support that moderate and regular exercise may protect BBB function through multidimensional mechanisms, offering novel insights and theoretical foundations for non-pharmacological therapies for neurological disorders.
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Study details
- Evidence strengthLow
How this study scored 43/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 24 of the 56 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neurobiology of disease) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41173152) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 24 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 24 of the 56 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
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