Evidence map›Paper›PMID 40702450›Full record

ArticleMolecular medicine (Cambridge, Mass.)2025

Tirzepatide mitigates Stroke-Induced Blood-Brain barrier disruption by modulating Claudin-1 and C/EBP-α pathways.

Duozi Wang, Jianhong Wang, Binghu Li, Shu Yang, Fuqiang Guo, Bo Zheng, Jian Wang

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular medicine (Cambridge, Mass.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07734792 (Effect of Tirzepatide on Functional Outcomes in Patients With Acute Ischemic Stroke Undergoing Endovascular Thrombectomy), which is not on this map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT07734792 phase2 / phase3not yet recruitingnot on this mapstarted 2026, after this paper: background citation

Effect of Tirzepatide on Functional Outcomes in Patients With Acute Ischemic Stroke Undergoing Endovascular Thrombectomy: A Multicenter, Randomized, Controlled, Blinded Outcome Assessment Trial

TypeinterventionalSponsoryifang zhuRan2026 to 2028Enrolled430ConditionsAcute Ischemic Stroke (AIS)ArmsTirzepatide, Standard Medical Care (SMC)
3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
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  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Duozi Wang *Department of Neurology, the Affiliated Hospital of University of Electronic Science and Technology, Sichuan Provincial People's Hospital, Chengdu, 610072, Sichuan, China.
Jianhong Wang *Department of Neurology, the Affiliated Hospital of University of Electronic Science and Technology, Sichuan Provincial People's Hospital, Chengdu, 610072, Sichuan, China.
Binghu LiDepartment of Neurology, the Affiliated Hospital of University of Electronic Science and Technology, Sichuan Provincial People's Hospital, Chengdu, 610072, Sichuan, China.
Shu YangDepartment of Neurology, the Affiliated Hospital of University of Electronic Science and Technology, Sichuan Provincial People's Hospital, Chengdu, 610072, Sichuan, China.
Fuqiang GuoDepartment of Neurology, the Affiliated Hospital of University of Electronic Science and Technology, Sichuan Provincial People's Hospital, Chengdu, 610072, Sichuan, China.
Bo ZhengDepartment of Neurology, the Affiliated Hospital of University of Electronic Science and Technology, Sichuan Provincial People's Hospital, Chengdu, 610072, Sichuan, China.
Jian Wang *Department of Neurology, Ya'an Peoples Hospital, No.9 Ankang Road, Ya'an, 625000, Sichuan, China. jianwang3260@126.com.

Funding

Central Government Guides Local Scientific and Technological Development Project Grant No. 2022ZYD0097Sichuan Medical Youth Innovation Research Project Grant No. Q21049Sichuan Provincial Health Commission Special Clinical Research Project Grant No. 23LCYJ034
6 · The paper itself

Abstract

backgroundStroke is a major cause of disability and mortality worldwide, with ischemic stroke (IS) being the most common form. The blood-brain barrier (BBB) plays a critical role in protecting the brain, and its dysfunction after stroke exacerbates neuronal damage. Therefore, restoring BBB integrity is a promising therapeutic strategy. Tirzepatide (TZP), a dual GLP-1 and GIP receptor agonist, has demonstrated neuroprotective effects, but its role in BBB restoration post-stroke remains unclear.

objectiveThis study aims to evaluate the potential of TZP in preventing BBB dysfunction and restoring its integrity in ischemic stroke models.

methodsUsing a middle cerebral artery occlusion (MCAO) mouse model of ischemic stroke, we assessed the effects of TZP on neurological deficits, BBB permeability, and the expression of tight junction (TJ) proteins, particularly Claudin-1. In vitro, human brain microvascular endothelial cells (HBMVECs) were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) to simulate ischemic conditions. The involvement of C/EBP-α, a key transcription factor regulating TJ proteins, was also investigated.

resultsTZP treatment significantly improved neurological scores and reduced BBB permeability in MCAO mice. It also restored Claudin-1 expression, which was downregulated in stroke conditions. In vitro, TZP reduced endothelial permeability and enhanced Claudin-1 expression in OGD/R-treated HBMVECs. Silencing C/EBP-α abolished the protective effects of TZP on both BBB integrity and Claudin-1 expression, indicating that C/EBP-α signaling is crucial for TZP's action.

conclusionTZP ameliorates BBB dysfunction and protects against ischemic stroke by activating C/EBP-α signaling and restoring Claudin-1-mediated tight junction integrity. These findings suggest that TZP holds promise as a therapeutic agent for stroke, offering a novel strategy for maintaining BBB function and reducing neuronal damage. Further studies are needed to explore the detailed mechanisms underlying TZP's neuroprotective effects and its clinical potential in stroke therapy.

Indexed as

Blood-Brain BarrierCCAAT-Enhancer-Binding ProteinsClaudin-1Neuroprotective AgentsSignal TransductionStrokeAnimalsDisease Models, AnimalEndothelial CellsHumansInfarction, Middle Cerebral ArteryMaleMiceMice, Inbred C57BLTirzepatideCCAAT-Enhancer-Binding ProteinsClaudin-1Neuroprotective AgentsTirzepatideBlood-brain barrier (BBB)C/EBP-αClaudin-1StrokeTirzepatide

Identifiers

PMID40702450
PMCPMC12285096

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.