Evidence map›Paper›PMID 39444090›Full record

ArticleBrain and behavior2024

The Activation of PKM2 Induces Pyroptosis in Hippocampal Neurons via the NLRP3/Caspase-1/GSDMD Pathway in Neonatal Rats With Hypoxic-Ischemic Brain Injury.

Sha Sha, Ni Jin, Ruiyu Zhou, Yanghao Ruan, Ying Ouyang

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Article in Brain and behavior, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

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7citing papers in PubMed
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3 · Its place in the literature

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7 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Sha ShaSun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.ORCID https://orcid.org/0009-0001-4078-3084
Ni JinSun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Ruiyu ZhouThe Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.ORCID https://orcid.org/0000-0003-3505-4829
Yanghao RuanThe Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China.
Ying OuyangSun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.

Funding

Kashgar Guangjian Group Co. Ltd.Minsheng Science and Technology Program of Guangzhou MunicipalityNatural Science Foundation of Guangdong Province 2021A1515010323Natural Science Foundation of Guangdong Province 2023A1515011904
6 · The paper itself

Abstract

introductionThe presence of hypoxic-ischemic brain damage (HIBD) in neonates triggers a strong neuroinflammatory reaction. Pyroptosis, a programmed cell death mechanism associated with inflammation, plays a crucial role in HIBD. Pyruvate kinase M2 (PKM2) plays a significant role in connecting metabolic processes and inflammatory responses, but whether it affects hippocampus pyroptosis in HIBD is unclear. The aim of this study is to elucidate the role of PKM2 in HIBD and to propose a novel therapeutic approach for neonatal ischemic-hypoxic encephalopathy.

methodsIn this study, we employed neonatal 7-day-old Sprague Dawley rats to establish a model of HIBD using the Rice-Vannucci surgical technique and a hypoxia device. To inhibit the elevation of PKM2, we utilized the PKM2 inhibitor shikonin. The rats were categorized into four groups: Sham, Shikonin, HIBD, and Shikonin + HIBD. Behavioral tests, hematoxylin eosin staining, immunofluorescence staining, ELISA (IL-1β, IL-18), and LDH were conducted in each group to evaluate neurological function, hippocampal damage, the occurrence of neuronal pyroptosis, and the neuroinflammation. Western blot was used to assess the expression levels of PKM2, NLRP3, Caspase-1, Cleaved Caspase-1, GSDMD, GSDMDN, and IL-1β.

resultsThe expression of PKM2 elevated in hippocampal tissues of the HIBD model and the localization of PKM2 in the hippocampus was activated in neurons instead of microglia during the HIBD. Meanwhile, the inhibition of PKM2 improved the behavioral test scores and the body weight of rats, the neuronal damage in the CA1 region of hippocampal tissue was also attenuated. In addition, inhibiting PKM2 alleviated neuronal pyroptosis by decreasing the expression of PKM2, NLRP3, Caspase-1, Cleaved Caspase-1, GSDMD, GSDMDN. Furthermore, serum levels of LDH and inflammatory factors IL-1β and IL-18 decrease with PKM2 inhibition.

conclusionsBased on these findings, we can conclude that PKM2 plays a crucial role in regulating hippocampal neuronal pyroptosis of HIBD rats via NLRP3/Caspase-1/GSDMD pathway. Therefore, inhibiting PKM2 could be a promising therapeutic strategy for the treatment of neonatal ischemic-hypoxic encephalopathy.

Indexed as

Animals, NewbornCaspase 1HippocampusHypoxia-Ischemia, BrainNeuronsNLR Family, Pyrin Domain-Containing 3 ProteinPyroptosisPyruvate KinaseRats, Sprague-DawleyAnimalsDisease Models, AnimalGasderminsIntracellular Signaling Peptides and ProteinsNaphthoquinonesPhosphate-Binding ProteinsRatsCaspase 1GasderminsGsdmd protein, ratIntracellular Signaling Peptides and ProteinsNaphthoquinonesNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, ratPhosphate-Binding ProteinsPkm protein, ratPyruvate Kinaseshikoninhypoxic‐ischemic brain damageNLRP3/Caspase‐1/GSDMDPKM2pyroptosis

Identifiers

PMID39444090
PMCPMC11499207

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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.