Evidence map›Paper›PMID 35002615›Full record

ArticleFrontiers in molecular neuroscience2021

Exendin-4 Preserves Blood-Brain Barrier Integrity

Zhiyi Xie, Budbazar Enkhjargal, Matei Nathanael, Lingyun Wu, Qiquan Zhu, Tongyu Zhang, Jiping Tang, John H Zhang

Open access · goldAbstract read
In one paragraph

Article in Frontiers in molecular neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.2field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Review
  6. Review
  7. Systemic Inflammation after Aneurysmal Subarachnoid Hemorrhage.International journal of molecular sciences · 2023
    Review
  8. Immunological Profile of Vasospasm after Subarachnoid Hemorrhage.International journal of molecular sciences · 2023
    Review
  9. Article
  10. Article
  11. Article
  12. Article
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

8 authors at 1 institution in 2 countries.

Zhiyi XieDepartment of Neurosurgery, The Second Affiliated Hospital, Zhejiang University, Hangzhou, China.
Budbazar EnkhjargalDepartment of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, United States.
Matei NathanaelDepartment of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, United States.
Lingyun WuDepartment of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, United States.
Qiquan ZhuDepartment of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, United States.
Tongyu ZhangDepartment of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, United States.
Jiping TangDepartment of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, United States.
John H ZhangDepartment of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, United States.
Loma Linda University · US

Funding

Vascular Biology Core FacilityP01NS082184 · NINDS · LOMA LINDA UNIVERSITY · PI PEARCE, WILLIAM J. · 2014 to 2018
$6.1M
Neurovascular Protection for Early Brain Injury after SAHR01NS081740 · NINDS · LOMA LINDA UNIVERSITY · PI ZHANG, JOHN H · 2013 to 2017
$1.6M
NINDS NIH HHS P01 NS082184NINDS NIH HHS R01 NS081740
6 · The paper itself

Abstract

In this study, we investigated the role of Exendin-4 (Ex-4), a glucagon-like peptide 1 receptor (GLP-1R) agonist, in blood-brain barrier (BBB) disruption after subarachnoid hemorrhage (SAH) in rats. The endovascular perforation model of SAH was performed in Sprague-Dawley rats. Ex-4 was intraperitoneally injected 1 h after SAH induction. To elucidate the underlying molecular mechanism, small interfering ribonucleic acid (siRNA) for GLP-1R and Dorsomorphin, a specific inhibitor of adenosine monophosphate-activated protein kinase (AMPK), were intracerebroventricularly injected 48 h before induction of SAH correspondingly. Immunofluorescence results supported GLP-1R expressed on the endothelial cells of microvessels in the brain after SAH. Administration of Ex-4 significantly reduced brain water content and Evans blue extravasation in both hemispheres, which improved neurological scores at 24 h after SAH. In the mechanism study, Ex-4 treatment significantly increased the expression of GLP-1R, p-AMPK, IκB-α, Occludin, and Claudin-5, while the expression of p-nuclear factor-kappa B (NF-κB) p65, matrix metalloproteinase-9 (MMP-9), and albumin was significantly decreased. The effects of Ex-4 were reversed by the intervention of GLP-1R siRNA or Dorsomorphin, respectively. In conclusion, Ex-4 could preserve the BBB integrity through GLP-1R/AMPK-dependent NF-κB/MMP-9 inhibition after SAH, which should be further investigated as a potential therapeutic target in SAH.

Indexed as

AMPKblood-brain barrierExendin-4GLP-1rsubarachnoid hemorrhage

Identifiers

PMID35002615
PMCPMC8733623
OpenAlexW4200486948

What OpenQuestion holds

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Registered trials

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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.