Evidence map›Paper›PMID 42504682›Full record

ArticleCNS neuroscience & therapeutics2026

Histone H3K18 Lactylation Contributes to Perioperative Neurocognitive Disorder Through Immune Checkpoint Lymphocyte Activation Gene 3 Mediated Microglial Pyroptosis.

Chenglong Li, Xi Gou, Yingying Zhao, Lina Zhang, Shuai Liu, Shenhui Deng, Qi Li, Sihua Qi

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Article in CNS neuroscience & therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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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

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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

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No citing paper in PubMed yet.

4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Chenglong LiDepartment of Anesthesiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Xi GouDepartment of Anesthesiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Yingying ZhaoDepartment of Anesthesiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Lina ZhangDepartment of Anesthesiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Shuai LiuDepartment of Anesthesiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Shenhui DengDepartment of Anesthesiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Qi LiDepartment of Anesthesiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Sihua QiDepartment of Anesthesiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.ORCID https://orcid.org/0000-0002-1481-7498

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsThis study investigates whether histone H3K18 lactylation (H3K18la) contributes to perioperative neurocognitive disorders (PND) by upregulating immune checkpoint Lymphocyte activation gene 3 (Lag3) and microglial pyroptosis, thereby aggravating neuroinflammation in the hippocampus.

methodsLactate levels and H3K18la expression were measured in mouse hippocampus after surgery. H3K18la downstream targets were identified by CUT&Tag and RNA-seq. After Lag3 silencing in BV2 cells, downstream pathways were screened and validated by RNA-seq and in vitro assays. Glycolysis inhibitors and Lag3 antibody were used to assess cognitive function and pyroptosis-related protein expression in postoperative mice.

resultsSurgery significantly elevated hippocampal lactate and H3K18la levels in mice. Inhibiting glycolysis led to a reduction in H3K18la and mitigated cognitive impairments in the PND model mice. CUT&Tag and RNA-seq revealed that H3K18la transcriptionally activates Lag3 by enriching at its promoter, and Lag3 blockade improved postoperative cognition. Furthermore, Lag3 upregulation triggered microglial pyroptosis via NOD-like receptor protein 3 (NLRP3) signaling, thereby aggravating neuroinflammation and promoting PND.

conclusionsSurgical trauma-induced increase of H3K18la in microglia promotes PND by upregulating Lag3 and triggering NLRP3-dependent microglial pyroptosis, highlighting the H3K18la-Lag3-NLRP3 axis as a therapeutic target for PND.

Indexed as

Antigens, CDHistonesMicrogliaNeurocognitive DisordersPyroptosisAnimalsHippocampusLymphocyte Activation Gene 3 ProteinMaleMiceMice, Inbred C57BLNLR Family, Pyrin Domain-Containing 3 ProteinAntigens, CDHistonesLymphocyte Activation Gene 3 ProteinNLR Family, Pyrin Domain-Containing 3 ProteinH3K18 lactylationLag3microgliaperioperative neurocognitive disorderpyroptosis

Identifiers

PMID42504682
PMCPMC13403156

What Socratic holds

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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 Socratic graph.