Evidence map›Paper›PMID 35922848›Full record

ArticleJournal of neuroinflammation2022

Aprepitant attenuates NLRC4-dependent neuronal pyroptosis via NK1R/PKCδ pathway in a mouse model of intracerebral hemorrhage.

Peng Jin, Dongqing Qi, Yuhui Cui, Cameron Lenahan, John H Zhang, Xiaogen Tao, Shuixiang Deng, Jiping Tang

Open access · goldAbstract read
In one paragraph

Article in Journal of neuroinflammation, 2022. 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
3.6field-weighted citation impact, top 6% 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, 31 citations in OpenAlex.

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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 2 institutions in 2 countries.

Peng Jin *Department of Intensive Care Unit, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China.
Dongqing Qi *Department of Rehabilitation Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China.
Yuhui CuiDepartment of Physiology and Pharmacology, Loma Linda University, Risley Hall, Room 219, 11041 Campus Street, Loma Linda, CA, 92354, USA.
Cameron LenahanBurrell College of Osteopathic Medicine, Las Cruces, NM, 88001, USA.
John H ZhangDepartment of Physiology and Pharmacology, Loma Linda University, Risley Hall, Room 219, 11041 Campus Street, Loma Linda, CA, 92354, USA.
Xiaogen TaoDepartment of Intensive Care Unit, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China. txg0724@163.com.
Shuixiang DengDepartment of Physiology and Pharmacology, Loma Linda University, Risley Hall, Room 219, 11041 Campus Street, Loma Linda, CA, 92354, USA. shuixiang2@126.com.
Jiping TangDepartment of Physiology and Pharmacology, Loma Linda University, Risley Hall, Room 219, 11041 Campus Street, Loma Linda, CA, 92354, USA. jtang@11u.edu.
Loma Linda University · USUniversity of Science and Technology of China · CN

Funding

Shuixiang Deng 21ZR1410700
6 · The paper itself

Abstract

backgroundPyroptosis is a programmed cell death mediated by inflammasomes. Previous studies have reported that inhibition of neurokinin receptor 1 (NK1R) exerted neuroprotection in several neurological diseases. Herein, we have investigated the role of NK1R receptor inhibition using Aprepitant to attenuate NLRC4-dependent neuronal pyroptosis after intracerebral hemorrhage (ICH), as well as the underlying mechanism.

methodsA total of 182 CD-1 mice were used. ICH was induced by injection of autologous blood into the right basal ganglia. Aprepitant, a selective antagonist of NK1R, was injected intraperitoneally at 1 h after ICH. To explore the underlying mechanism, NK1R agonist, GR73632, and protein kinase C delta (PKCδ) agonist, phorbol 12-myristate 13-acetate (PMA), were injected intracerebroventricularly at 1 h after ICH induction, and small interfering ribonucleic acid (siRNA) for NLRC4 was administered via intracerebroventricular injection at 48 h before ICH induction, respectively. Neurobehavioral tests, western blot, and immunofluorescence staining were performed.

resultsThe expression of endogenous NK1R and NLRC 4 were gradually increased after ICH. NK1R was expressed on neurons. Aprepitant significantly improved the short- and long-term neurobehavioral deficits after ICH, which was accompanied with decreased neuronal pyroptosis, as well as decreased expression of NLRC4, Cleaved-caspase-1, GSDMD (gasdermin D), IL-1β, and IL-18. Activation of NK1R or PKCδ abolished these neuroprotective effects of Aprepitant after ICH. Similarly, knocking down NLRC4 using siRNA produced similar neuroprotective effects.

conclusionAprepitant suppressed NLRC4-dependent neuronal pyroptosis and improved neurological function, possibly mediated by inhibition of NK1R/PKCδ signaling pathways after ICH. The NK1R may be a promising therapeutic target for the treatment of ICH.

Indexed as

Neuroprotective AgentsPyroptosisAnimalsAprepitantCerebral HemorrhageDisease Models, AnimalMiceNeuronsRNA, Small InterferingAprepitantNeuroprotective AgentsRNA, Small InterferingAprepitantInflammasomeIntracerebral hemorrhageNeurokinin receptor 1Pyroptosis

Identifiers

PMID35922848
PMCPMC9351153
OpenAlexW4289550021

What Socratic 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 Socratic graph.