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Targeting CD38 to alleviate brain endothelial cell dysfunction and cognitive impairment in vascular dementia
Mingjing Yu, Zhi Qi, Jiaxin Zhang, Ziyi Zhang, Jieli Chen, Tao Yan, Zhili Chen. Journal of Pharmacological Sciences, 2025-05-21
Topic: Brain proteins, microglia and lab models
Vascular dementia (VaD) is a leading cause of cognitive decline, closely associated with cerebrovascular endothelial cell (CEC) dysfunction, blood-brain barrier (BBB) disruption, and neuroinflammation. CD38, an enzyme implicated in neuroinflammation and cellular senescence, has emerged as a potential regulator of these pathological processes, yet its role in CEC dysfunction within the context of VaD remains unclear. In this study, we investigated the impact of CD38 on CEC dysfunction using a mouse model of VaD induced by bilateral common carotid artery stenosis (BCAS). Our results demonstrate that BCAS significantly reduces cerebral blood flow (CBF), increases BBB permeability, and induces cognitive deficits, all accompanied by elevated CD38 expression in CECs and heightened levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). Notably, treatment with the selective CD38 inhibitor 78c (10 mg/kg, twice daily for 1 month) effectively mitigated these effects, reducing white matter damage, improving CBF, enhancing the expression of CEC tight junction proteins, and decreasing neuroinflammation and BBB disruption. In vitro experiments further revealed that 78c attenuates TNF-α-induced CD38 expression and inflammatory responses in CECs, likely through the NOX4/eNOS aixs. These findings identify CD38 as a crucial mediator of CEC dysfunction in VaD, linking chronic cerebral hypoperfusion to neurovascular damage.
Key findings
- Vascular dementia (VaD) is a leading cause of cognitive decline, closely associated with cerebrovascular endothelial cell (CEC) dysfunction, blood-brain barrier (BBB) disruption, and neuroinflammation.
- Our results demonstrate that BCAS significantly reduces cerebral blood flow (CBF), increases BBB permeability, and induces cognitive deficits, all accompanied by elevated CD38 expression in CECs and heightened levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α).
- In vitro experiments further revealed that 78c attenuates TNF-α-induced CD38 expression and inflammatory responses in CECs, likely through the NOX4/eNOS aixs.
- These findings identify CD38 as a crucial mediator of CEC dysfunction in VaD, linking chronic cerebral hypoperfusion to neurovascular damage.
Why it matters
In a mouse model of vascular dementia, the CD38 inhibitor 78c reduced white matter damage, improved blood flow, and decreased neuroinflammation and blood-brain barrier disruption. This is animal and cell research on vascular dementia, so it does not yet show a treatment for Alzheimer's disease in people.
Study details
- Evidence strengthLow
How this study scored 36/100
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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Pharmacological Sciences) |
| Journal's citation record | 1 / 4 | Journal of Pharmacological Sciences: journal h-index 106 (OpenAlex, 2026-10-29) |
| 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 | 2 / 7 | Cited 6 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 1.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 6 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Zhili Chen: h-index 20 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Tianjin Medical University: institution h-index 402 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40543993) |
| Free to read | 2 / 2 | Free to read |
| Total | 36 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.jphs.2025.05.013
- PubMed: 40543993
- Original source →
- Free full text: Journal of Pharmacological Sciences →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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.
APA 7th
Yu, M., Qi, Z., Zhang, J., Zhang, Z., Chen, J., Yan, T., et al. (2025). Targeting CD38 to alleviate brain endothelial cell dysfunction and cognitive impairment in vascular dementia. Journal of Pharmacological Sciences. https://doi.org/10.1016/j.jphs.2025.05.013
Vancouver
Yu M, Qi Z, Zhang J, Zhang Z, Chen J, Yan T, et al. Targeting CD38 to alleviate brain endothelial cell dysfunction and cognitive impairment in vascular dementia. Journal of Pharmacological Sciences. 2025. doi:10.1016/j.jphs.2025.05.013. PMID: 40543993.
BibTeX
@article{yu2025-40543993,
author = {Yu, Mingjing and Qi, Zhi and Zhang, Jiaxin and Zhang, Ziyi and Chen, Jieli and Yan, Tao and Chen, Zhili},
title = {{Targeting CD38 to alleviate brain endothelial cell dysfunction and cognitive impairment in vascular dementia}},
journal = {Journal of Pharmacological Sciences},
year = {2025},
doi = {10.1016/j.jphs.2025.05.013},
pmid = {40543993},
url = {https://doi.org/10.1016/j.jphs.2025.05.013}
}
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