Evidence map›Paper›PMID 28092085›Full record

ArticleMolecular neurobiology2018

Evidence that NF-κB and MAPK Signaling Promotes NLRP Inflammasome Activation in Neurons Following Ischemic Stroke.

David Yang-Wei Fann, Yun-An Lim, Yi-Lin Cheng, Ker-Zhing Lok, Prasad Chunduri, Sang-Ha Baik, Grant R Drummond, S Thameem Dheen, Christopher G Sobey, Dong-Gyu Jo and 2 more

Abstract read
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In one paragraph

Article in Molecular neurobiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 189 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
189citing papers in PubMed, 1 pooled it
11.8field-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

189 citing papers in PubMed, 1 synthesis or guideline pooled it, 315 citations in OpenAlex.

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129 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

12 authors at 4 institutions in 3 countries.

David Yang-Wei FannDepartment of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, MD9, Singapore, Singapore.
Yun-An LimDepartment of Pharmacology, National University of Singapore, Singapore, Singapore.
Yi-Lin ChengDepartment of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, MD9, Singapore, Singapore.
Ker-Zhing LokDepartment of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, MD9, Singapore, Singapore.
Prasad ChunduriSchool of Biomedical Sciences, The University of Queensland, St Lucia, QLD, 4072, Australia.
Sang-Ha BaikSchool of Pharmacy, Sungkyunkwan University, Suwon, South Korea.
Grant R DrummondDepartment of Pharmacology, Monash University, Clayton, VIC, Australia.
S Thameem DheenDepartment of Anatomy, The Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Christopher G SobeyDepartment of Pharmacology, Monash University, Clayton, VIC, Australia.
Dong-Gyu JoSchool of Pharmacy, Sungkyunkwan University, Suwon, South Korea.
Christopher Li-Hsian ChenDepartment of Pharmacology, National University of Singapore, Singapore, Singapore.
Thiruma V ArumugamDepartment of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, MD9, Singapore, Singapore. phstva@nus.edu.sg.
National University of Singapore · SGSungkyunkwan University · KRMonash University · AUUniversity of Queensland · AU

Funding

Ministry of Education - Singapore R-185-000-255-112Ministry of Education - Singapore R-185-000-285-112National Medical Research Council NMRC-CBRG-0102/2016National Medical Research Council NMRC/CG/013/2013
6 · The paper itself

Abstract

Multi-protein complexes, termed "inflammasomes," are known to contribute to neuronal cell death and brain injury following ischemic stroke. Ischemic stroke increases the expression and activation of nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) Pyrin domain containing 1 and 3 (NLRP1 and NLRP3) inflammasome proteins and both interleukin (IL)-1β and IL-18 in neurons. In this study, we provide evidence that activation of either the NF-κB and MAPK signaling pathways was partly responsible for inducing the expression and activation of NLRP1 and NLRP3 inflammasome proteins and that these effects can be attenuated using pharmacological inhibitors of these two pathways in neurons and brain tissue under in vitro and in vivo ischemic conditions, respectively. Moreover, these findings provided supporting evidence that treatment with intravenous immunoglobulin (IVIg) preparation can reduce activation of the NF-κB and MAPK signaling pathways resulting in decreased expression and activation of NLRP1 and NLRP3 inflammasomes, as well as increasing expression of anti-apoptotic proteins, Bcl-2 and Bcl-xL, in primary cortical neurons and/or cerebral tissue under in vitro and in vivo ischemic conditions. In summary, these results provide compelling evidence that both the NF-κB and MAPK signaling pathways play a pivotal role in regulating the expression and activation of NLRP1 and NLRP3 inflammasomes in primary cortical neurons and brain tissue under ischemic conditions. In addition, treatment with IVIg preparation decreased the activation of the NF-κB and MAPK signaling pathways, and thus attenuated the expression and activation of NLRP1 and NLRP3 inflammasomes in primary cortical neurons under ischemic conditions. Hence, these findings suggest that therapeutic interventions that target inflammasome activation in neurons may provide new opportunities in the future treatment of ischemic stroke.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsAnthracenesApoptosis Regulatory ProteinsBrainBrain IschemiaButadienesExtracellular Signal-Regulated MAP KinasesImidazolesInflammasomesMiceNeuronsNF-kappa BNitrilesNLR Family, Pyrin Domain-Containing 3 ProteinPyridines3-(4-methylphenylsulfonyl)-2-propenenitrileAdaptor Proteins, Signal TransducingAnthracenesApoptosis Regulatory ProteinsButadienesExtracellular Signal-Regulated MAP KinasesImidazolesInflammasomesNALP1 protein, mouseNF-kappa BNitrilesNLR Family, Pyrin Domain-Containing 3 ProteinpyrazolanthronePyridinesSB 203580SulfonesU 0126InflammasomeMitogen-activated protein kinasesNeuronal cell deathNLRPNuclear factor kappa BStroke

Identifiers

PMID28092085
OpenAlexW2577038661

What OpenQuestion holds

Textmetadata
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.