Evidence map›Paper›PMID 34930895›Full record

ArticleCell death & disease2021

NLPR3 inflammasome inhibition alleviates hypoxic endothelial cell death in vitro and protects blood-brain barrier integrity in murine stroke.

Maximilian Bellut, Lena Papp, Michael Bieber, Peter Kraft, Guido Stoll, Michael K Schuhmann

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed
6.0field-weighted citation impact, top 2% 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

81 citing papers in PubMed, 123 citations in OpenAlex.

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21 more citing papers are in PubMed but not listed here.

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

6 authors at 2 institutions in 1 country.

Maximilian BellutDepartment of Neurology, University Hospital Wuerzburg, Josef-Schneider-Str. 11, 97080, Würzburg, Germany.ORCID 0000-0002-6462-9495
Lena PappDepartment of Neurology, University Hospital Wuerzburg, Josef-Schneider-Str. 11, 97080, Würzburg, Germany.ORCID 0000-0003-4350-3655
Michael BieberDepartment of Neurology, University Hospital Wuerzburg, Josef-Schneider-Str. 11, 97080, Würzburg, Germany.ORCID 0000-0002-5535-6480
Peter KraftDepartment of Neurology, University Hospital Wuerzburg, Josef-Schneider-Str. 11, 97080, Würzburg, Germany.
Guido StollDepartment of Neurology, University Hospital Wuerzburg, Josef-Schneider-Str. 11, 97080, Würzburg, Germany.
Michael K SchuhmannDepartment of Neurology, University Hospital Wuerzburg, Josef-Schneider-Str. 11, 97080, Würzburg, Germany. schuhmann_m@ukw.de.ORCID 0000-0002-4014-7010
Universitätsklinikum Würzburg · DEUniversitäts-Kinderklinik Würzburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In ischemic stroke (IS) impairment of the blood-brain barrier (BBB) has an important role in the secondary deterioration of neurological function. BBB disruption is associated with ischemia-induced inflammation, brain edema formation, and hemorrhagic infarct transformation, but the underlying mechanisms are incompletely understood. Dysfunction of endothelial cells (EC) may play a central role in this process. Although neuronal NLR-family pyrin domain-containing protein 3 (NLRP3) inflammasome upregulation is an established trigger of inflammation in IS, the contribution of its expression in EC is unclear. We here used brain EC, exposed them to oxygen and glucose deprivation (OGD) in vitro, and analyzed their survival depending on inflammasome inhibition with the NLRP3-specific drug MCC950. During OGD, EC death could significantly be reduced when targeting NLRP3, concomitant with diminished endothelial NLRP3 expression. Furthermore, MCC950 led to reduced levels of Caspase 1 (p20) and activated Gasdermin D as markers for pyroptosis. Moreover, inflammasome inhibition reduced the secretion of pro-inflammatory chemokines, cytokines, and matrix metalloproteinase-9 (MMP9) in EC. In a translational approach, IS was induced in C57Bl/6 mice by 60 mins transient middle cerebral artery occlusion and 23 hours of reperfusion. Stroke volume, functional outcome, the BBB integrity, and-in good agreement with the in vitro results-MMP9 secretion as well as EC survival improved significantly in MCC950-treated mice. In conclusion, our results establish the NLRP3 inflammasome as a critical pathogenic effector of stroke-induced BBB disruption by activating inflammatory signaling cascades and pyroptosis in brain EC.

Indexed as

AnimalsBlood-Brain BarrierBrain InfarctionCell HypoxiaCells, CulturedDisease Models, AnimalEndothelial CellsFuransGlucoseIndenesInflammasomesInjections, IntraperitonealIschemic StrokeMaleMiceMice, Inbred C57BLFuransGlucoseIndenesInflammasomesN-(1,2,3,5,6,7-hexahydro-S-indacen-4-ylcarbamoyl)-4-(2-hydroxy-2-propanyl)-2-furansulfonamideNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseProtective AgentsSulfonamides

Identifiers

PMID34930895
PMCPMC8688414
OpenAlexW4200178440

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.