Evidence map›Paper›PMID 28963039›Full record

ArticleNeuropharmacology2018

Ketamine induces hippocampal apoptosis through a mechanism associated with the caspase-1 dependent pyroptosis.

Zhi Ye, Qing Li, Qulian Guo, Yunchuan Xiong, Dong Guo, Hong Yang, Yan Shu

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

Article in Neuropharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
3.1field-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

33 citing papers in PubMed, 57 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

7 authors at 2 institutions in 2 countries.

Zhi YeDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD, USA; Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, 410078, China.
Qing LiDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD, USA; Institute of Clinical Pharmacology, Central South University, Hunan 410078, China.
Qulian GuoDepartment of Anesthesiology, Xiangya Hospital, Central South University, Changsha, 410078, China.
Yunchuan XiongDepartment of Anesthesiology, Xiangya Hospital, Central South University, Changsha, 410078, China.
Dong GuoDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD, USA.
Hong YangDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD, USA.
Yan ShuDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD, USA. Electronic address: yshu@rx.umaryland.edu.
University of Maryland, Baltimore · USCentral South University · CN

Funding

Xenobiotic Transporter Regulation and IRIP FunctionR01GM099742 · NIGMS · UNIVERSITY OF MARYLAND BALTIMORE · PI SHU, YAN · 2012 to 2016
$1.6M
NIGMS NIH HHS R01 GM099742
6 · The paper itself

Abstract

Ketamine, a pediatric anesthetic, is widely used in clinical practice. There was growing evidence showing that ketamine can promote neuronal death in developing brains of both humans and animals. In this study, we used in vivo neonatal and juvenile mouse models to induce ketamine-related neurotoxicity in the hippocampus. Active caspase-3 and -9 proteins, which are responsible for the release of cytochrome C, and the mitochondrial translocation of p53, which is associated with mitochondrial apoptosis, were found to be significantly up-regulated in the ketamine-induced hippocampal neurotoxicity. Furthermore, we demonstrated that the levels of pyroptosis-related proteins, including caspase-1 and -11, NOD-like receptor family, pyrin domain containing 3 (NLRP3), and IL-1β and IL-18, significantly increased after multiple doses of ketamine administration. We speculated that ketamine triggered the formation of NLRP3 and caspase-1 complex and its translocation to the mitochondria. In consistent with this, ketamine treatment was found to induce pyroptosis in mouse primary hippocampal neurons, which was characterized by increased pore formation and elevated lactate dehydrogenase release in mitochondria. Silencing caspase-1 with lentivirus-mediated short hairpin RNA (shRNA) significantly decreased the levels of not only pyroptosis-related proteins but also mitochondrial apoptosis-associated proteins in mouse primary hippocampal neurons. We conclude that caspase-1-dependent pyroptosis is an important event which may be an essential pathway involved in the mitochondria-associated apoptosis in ketamine-induced hippocampal neurotoxicity.

Indexed as

Analysis of VarianceAnimalsAnimals, NewbornApoptosisCaspase 1Dose-Response Relationship, DrugEmbryo, MammalianExcitatory Amino Acid AntagonistsHippocampusImmunoprecipitationInterleukin-1betaKetamineL-Lactate DehydrogenaseMiceMice, Inbred C57BLMitochondriaCaspase 1Excitatory Amino Acid AntagonistsInterleukin-1betaKetamineL-Lactate DehydrogenaseNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseReceptors, Cell SurfaceApoptosisCaspase-1HippocampusKetamineNeurotoxicityPyroptosis

Identifiers

PMID28963039
PMCPMC5714696
OpenAlexW2758628359

What OpenQuestion holds

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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.