Evidence map›Paper›PMID 33531049›Full record

ArticleJournal of neuroinflammation2021

TGR5 activation attenuates neuroinflammation via Pellino3 inhibition of caspase-8/NLRP3 after middle cerebral artery occlusion in rats.

Hui Liang, Nathanael Matei, Devin W McBride, Yang Xu, Zhenhua Zhou, Jiping Tang, Benyan Luo, John H Zhang

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

22 citing papers in PubMed, 39 citations in OpenAlex.

  1. Taurochenodeoxycholic acid alleviates MPPIBRO neuroscience reports · 2026
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  6. Emerging Roles of Bile Acids in Neuroinflammation.International journal of molecular sciences · 2025
    Review
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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 3 institutions in 2 countries.

Hui LiangDepartment of Neurology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Nathanael MateiDepartment of Physiology and Pharmacology and Department of Anesthesiology, Loma Linda University, 11041 Campus St, Risley Hall, Room 219, Loma Linda, CA, 92354, USA.
Devin W McBrideThe Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Yang XuDepartment of Physiology and Pharmacology and Department of Anesthesiology, Loma Linda University, 11041 Campus St, Risley Hall, Room 219, Loma Linda, CA, 92354, USA.
Zhenhua ZhouDepartment of Physiology and Pharmacology and Department of Anesthesiology, Loma Linda University, 11041 Campus St, Risley Hall, Room 219, Loma Linda, CA, 92354, USA.
Jiping TangDepartment of Physiology and Pharmacology and Department of Anesthesiology, Loma Linda University, 11041 Campus St, Risley Hall, Room 219, Loma Linda, CA, 92354, USA.
Benyan LuoDepartment of Neurology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. luobenyan@zju.edu.cn.
John H ZhangDepartment of Physiology and Pharmacology and Department of Anesthesiology, Loma Linda University, 11041 Campus St, Risley Hall, Room 219, Loma Linda, CA, 92354, USA.
Loma Linda University · USFirst Affiliated Hospital Zhejiang University · CNThe University of Texas Health Science Center at Houston · US

Funding

Vascular Biology Core FacilityP01NS082184 · NINDS · LOMA LINDA UNIVERSITY · PI ZHANG, JOHN H · 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

backgroundNucleotide-binding oligomerization domain-like receptor pyrin domain-containing protein 3 (NLRP3) plays an important role in mediating inflammatory responses during ischemic stroke. Bile acid receptor Takeda-G-protein-receptor-5 (TGR5) has been identified as an important component in regulating brain inflammatory responses. In this study, we investigated the mechanism of TGR5 in alleviating neuroinflammation after middle cerebral artery occlusion (MCAO).

methodsSprague-Dawley rats were subjected to MCAO and TGR5 agonist INT777 was administered intranasally 1 h after MCAO. Small interfering RNAs (siRNA) targeting TGR5 and Pellino3 were administered through intracerebroventricular injection 48 h before MCAO. Infarct volumes and neurologic scores were evaluated, and ELISA, flow cytometry, immunofluorescence staining, immunoblotting, and co-immunoprecipitation were used for the evaluations.

resultsEndogenous TGR5 and Pellino3 levels increased after MCAO. TGR5 activation by INT777 significantly decreased pro-inflammatory cytokine, cleaved caspase-8, and NLRP3 levels, thereby reducing brain infarctions; both short- and long-term neurobehavioral assessments showed improvements. Ischemic damage induced the interaction of TGR5 with Pellino3. Knockdown of either TGR5 or Pellino3 increased the accumulation of cleaved caspase-8 and NLRP3, aggravated cerebral impairments, and abolished the anti-inflammatory effects of INT777 after MCAO.

conclusionsTGR5 activation attenuated brain injury by inhibiting neuroinflammation after MCAO, which could be mediated by Pellino3 inhibition of caspase-8/NLRP3.

Indexed as

Administration, IntranasalAnimalsBrainCaspase 8Cholic AcidsInfarction, Middle Cerebral ArteryInflammation MediatorsInjections, IntraventricularMaleNLR Family, Pyrin Domain-Containing 3 ProteinRatsRats, Sprague-DawleyReceptors, G-Protein-CoupledRNA, Small InterferingUbiquitin-Protein Ligases6alpha-ethyl-23(S)-methylcholic acidCasp8 protein, ratCaspase 8Cholic AcidsGpbar1 protein, ratInflammation MediatorsNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, ratPELI3 protein, mouseReceptors, G-Protein-CoupledRNA, Small InterferingUbiquitin-Protein LigasesEarly brain injuryInflammationMiddle cerebral artery occlusionNeuroprotectionTGR5

Identifiers

PMID33531049
PMCPMC7856773
OpenAlexW3114024317

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.