Evidence map›Paper›PMID 42684584›Full record

ArticleNeurochemical research2026

SIRT1 Activation Ameliorates Neuroinflammation and Cognitive Impairment in a Murine SAE Model and is Associated with the Nrf2/GPX4 Pathway.

Yue Zhang, Qingzhen Liu, Haishu Zhao, Zhi Liu, Mengna Liu, Yao Ning, Qing Ji, Lidong Zhang

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Article in Neurochemical research, 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

What it found

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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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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.

Yue Zhang *Department of Jinling Clinical Medical College, Nanjing Medical University, Nanjing, 210002, China.
Qingzhen Liu *Department of Anesthesiology, Affiliated Hospital of Medical School, Jinling Hospital, Nanjing University, Nanjing, 210002, Jiangsu Province, China.
Haishu ZhaoDepartment of Anesthesiology, Affiliated Hospital of Medical School, Jinling Hospital, Nanjing University, Nanjing, 210002, Jiangsu Province, China.
Zhi LiuDepartment of Anesthesiology, Affiliated Hospital of Medical School, Jinling Hospital, Nanjing University, Nanjing, 210002, Jiangsu Province, China.
Mengna LiuDepartment of Jinling Clinical Medical College, Nanjing Medical University, Nanjing, 210002, China.
Yao NingDepartment of Anesthesiology, Affiliated Hospital of Medical School, Jinling Hospital, Nanjing University, Nanjing, 210002, Jiangsu Province, China.
Qing JiDepartment of Anesthesiology, Affiliated Hospital of Medical School, Jinling Hospital, Nanjing University, Nanjing, 210002, Jiangsu Province, China. qing_ji@nju.edu.cn.
Lidong ZhangDepartment of Jinling Clinical Medical College, Nanjing Medical University, Nanjing, 210002, China. ldzhang1968@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Sepsis-associated encephalopathy (SAE) is a devastating condition with high mortality and cognitive sequelae, yet no effective treatments. This study investigates the neuroprotective potential of selective Sirtuin 1 (SIRT1) activation using the synthetic agonist SRT1720 in a male C57BL/6 J murine model of SAE. Transcriptomic profiling of the hippocampus revealed a specific disruption in glutathione and arachidonic acid metabolism pathways, indicating a metabolic priming for ferroptosis. We demonstrate that SIRT1 activation improves survival and ameliorates cognitive deficits by concurrently attenuating hippocampal ferroptosis and neuroinflammation. We observed that this protection was associated with the upregulated protein expression of Nrf2 and GPX4, key regulators of ferroptosis. Mechanistically, SIRT1 activation suppressed hippocampal ferroptosis, marked by reduced lipid peroxidation (ROS and MDA). Concurrently, it attenuated neuroinflammation by suppressing microglial activation and NLRP3 inflammasome activity, thereby decreasing the maturation of proinflammatory cytokines. These findings suggest SIRT1 activation coordinately counteracts both ferroptotic and inflammatory damage in SAE, presenting a compelling therapeutic strategy.

Indexed as

Cognitive DysfunctionNeuroinflammatory DiseasesNF-E2-Related Factor 2Phospholipid Hydroperoxide Glutathione PeroxidaseSepsis-Associated EncephalopathySirtuin 1AnimalsDisease Models, AnimalFerroptosisHeterocyclic Compounds, 4 or More RingsHippocampusMaleMiceMice, Inbred C57BLSignal Transductionglutathione peroxidase 4, mouseHeterocyclic Compounds, 4 or More RingsNfe2l2 protein, mouseNF-E2-Related Factor 2Phospholipid Hydroperoxide Glutathione PeroxidaseSirt1 protein, mouseSirtuin 1SRT1720FerroptosisNeuroinflammationSepsis-associated encephalopathySIRT1

Identifiers

PMID42684584

What Socratic holds

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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 Socratic graph.