Evidence map›Paper›PMID 23816751›Full record

ArticleNeurobiology of disease2013

P2X7R/cryopyrin inflammasome axis inhibition reduces neuroinflammation after SAH.

Sheng Chen, Qingyi Ma, Paul R Krafft, Qin Hu, William Rolland, Prativa Sherchan, Jianmin Zhang, Jiping Tang, John H Zhang

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

Article in Neurobiology of disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed
9.7field-weighted citation impact, top 1% 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

87 citing papers in PubMed, 136 citations in OpenAlex.

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27 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

9 authors at 2 institutions in 2 countries.

Sheng ChenDepartment of Neurosurgery, Zhejiang University, Hangzhou, Zhejiang, China.
Qingyi Ma
Paul R Krafft
Qin Hu
William Rolland
Prativa Sherchan
Jianmin Zhang
Jiping Tang
John H Zhang
Loma Linda University · USSecond Affiliated Hospital of Zhejiang University · CN

Funding

Neurovascular Protection for Subarachnoid HemorrhageR01NS053407 · NINDS · LOMA LINDA UNIVERSITY · PI ZHANG, JOHN H · 2006 to 2010
$1.8M
Neurovascular Protection for Early Brain Injury after SAHR01NS081740 · NINDS · LOMA LINDA UNIVERSITY · PI ZHANG, JOHN H · 2013 to 2017
$1.6M
NINDS NIH HHS NS053407NINDS NIH HHS R01 NS053407NINDS NIH HHS R01 NS081740
6 · The paper itself

Abstract

Neuroinflammation contributes to the pathogenesis of early brain injury (EBI) after subarachnoid hemorrhage (SAH). Cytotoxic events following SAH, such as extracellular accumulation of adenosine triphosphate (ATP), may activate the P2X purinoceptor 7 (P2X7R)/cryopyrin inflammasome axis, thus inducing the proinflammatory cytokine IL-1β/IL-18 secretion. We therefore hypothesized that inhibition of P2X7R/cryopyrin inflammasome axis would ameliorate neuroinflammation after SAH. In the present study, SAH was induced by the endovascular perforation in rats. Small interfering RNAs (siRNAs) of P2X7R or cryopyrin were administered intracerebroventricularly 24h before SAH. Brilliant blue G (BBG), a non-competitive antagonist of P2X7R, was administered intraperitoneally 30min following SAH. Post-assessments including SAH severity score, neurobehavioral test, brain water content, Western blot and immunofluorescence, were performed. Administration of P2X7R and cryopyrin siRNA as well as pharmacologic blockade of P2X7R by BBG ameliorated neurological deficits and brain edema at 24h following SAH. Inhibition of P2X7R/cryopyrin inflammasome axis suppressed caspase-1 activation, which subsequently decreased maturation of IL-1β/IL-18. To investigate the link between P2X7R and cryopyrin inflammasome in vivo, Benzoylbenzoyl-ATP (BzATP), a P2X7R agonist, was given to lipopolysaccharide (LPS) primed naive rats with scramble or cryopyrin siRNAs. In LPS-primed naive rats, BzATP induced caspase-1 activation and mature IL-1β release were neutralized by cryopyrin siRNA. Thus, the P2X7R/cryopyrin inflammasome axis may contribute to neuroinflammation via activation of caspase-1 and thereafter mature IL-1β/IL-18 production following SAH. Therapeutic interventions targeting P2X7R/cryopyrin pathway may be a novel approach to ameliorate EBI following SAH.

Indexed as

EncephalitisReceptors, Cytoplasmic and NuclearReceptors, Purinergic P2X7Signal TransductionSubarachnoid HemorrhageAdenosine TriphosphateAnimalsBrain EdemaCarrier ProteinsCytokinesDisease Models, AnimalDose-Response Relationship, DrugInjections, IntraventricularLipopolysaccharidesMaleNLR Family, Pyrin Domain-Containing 3 Protein3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphateAdenosine TriphosphateCarrier Proteinscoomassie Brilliant BlueCytokinesLipopolysaccharidesNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, ratPlatelet Aggregation InhibitorsReceptors, Cytoplasmic and NuclearReceptors, Purinergic P2X7RNA, Small InterferingRosaniline Dyesadenosine triphosphateanalysis of varianceANOVAapoptosis-associated speck-like protein containing a CAEDASCATPBBGBenzoylbenzoyl-ATPBrilliant blue GBzATPcentral nervous systemCNSCryopyrinearly brain injuryEarly brain injuryEBIEdemaIACUCIL-1βInflammationInstitutional Animal Care and Use Committeeinterleukin-1βlipopolysaccharideLPSMPOmyeloperoxidaseNF-κBNLRnuclear factor-kappa Bnucleotide-binding domain, leucine-rich repeat containingP2X7RP2X purinoceptor 7SAHSDsiRNAsmall interfering RNASprague–Dawleysubarachnoid hemorrhageSubarachnoid hemorrhageTLR4Toll-like receptor 4

Identifiers

PMID23816751
PMCPMC3771387
OpenAlexW2062780433

What OpenQuestion holds

Textmetadata
LicenceTDM
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.