Evidence map›Paper›PMID 39179968›Full record

ArticleMolecular medicine (Cambridge, Mass.)2024

Caspase-11 signaling promotes damage to hippocampal CA3 to enhance cognitive dysfunction in infection.

Ni Liang, Yi Li, Chuang Yuan, Xiaoli Zhong, Yanliang Yang, Fang Liang, Kai Zhao, Fangfang Yuan, Jian Shi, Erhua Wang and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular medicine (Cambridge, Mass.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
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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

14 authors.

Ni Liang *Department of Critical Care Medicine and Hematology, The 3Rd Xiangya Hospital, Central South University, Changsha, 410000, People's Republic of China.
Yi Li *Department of Critical Care Medicine and Hematology, The 3Rd Xiangya Hospital, Central South University, Changsha, 410000, People's Republic of China.
Chuang YuanXiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410000, People's Republic of China.
Xiaoli ZhongICU Center, The Second Xiangya Hospital, Central South University, Changsha, 410000, People's Republic of China.
Yanliang YangDepartment of Physiology, School of Basic Medical Science, Central South University, Changsha, 410000, People's Republic of China.
Fang LiangDepartment of Critical Care Medicine and Hematology, The 3Rd Xiangya Hospital, Central South University, Changsha, 410000, People's Republic of China.
Kai ZhaoDepartment of Critical Care Medicine and Hematology, The 3Rd Xiangya Hospital, Central South University, Changsha, 410000, People's Republic of China.
Fangfang YuanDepartment of Critical Care Medicine and Hematology, The 3Rd Xiangya Hospital, Central South University, Changsha, 410000, People's Republic of China.
Jian ShiDepartment of Critical Care Medicine and Hematology, The 3Rd Xiangya Hospital, Central South University, Changsha, 410000, People's Republic of China.
Erhua WangDepartment of Critical Care Medicine and Hematology, The 3Rd Xiangya Hospital, Central South University, Changsha, 410000, People's Republic of China.
Yanjun ZhongICU Center, The Second Xiangya Hospital, Central South University, Changsha, 410000, People's Republic of China.
Guixiang TianDepartment of Ultrasound, The Second Xiangya Hospital of Central South University, Changsha, 410000, People's Republic of China.
Ben LuDepartment of Critical Care Medicine and Hematology, The 3Rd Xiangya Hospital, Central South University, Changsha, 410000, People's Republic of China.
Yiting TangDepartment of Physiology, School of Basic Medical Science, Central South University, Changsha, 410000, People's Republic of China. yitingtang@csu.edu.cn.ORCID 0000-0002-6878-4775

Funding

Huxiang Youth Talent Support Program 2022RC1208Key Scientific Project of Hunan Province 2022SK2056National Natural Science Foundation of China 81971893National Natural Science Foundation of China 82002397National Natural Science Foundation of China 82072153National Natural Science Foundation of China 82272218National Science Foundation of Hunan Province in China 2020JJ4852National Science Foundation of Hunan Province in China 2021JJ40896Postgraduate Research and Innovation Project of Central South University 2021zzts1087Science Fund for Distinguished Young Scholars of Hunan Province 2022JJ10088Science Fund for Distinguished Young Scholars of Hunan Province 2023JJ10093
6 · The paper itself

Abstract

backgroundCognitive dysfunction caused by infection frequently emerges as a complication in sepsis survivor patients. However, a comprehensive understanding of its pathogenesis remains elusive.

methodsIn our in vivo experiments, an animal model of endotoxemia was employed, utilizing the Novel Object Recognition Test and Morris Water Maze Test to assess cognitive function. Various techniques, including immunofluorescent staining, Western blotting, blood‒brain barrier permeability assessment, Limulus Amebocyte Lysate (LAL) assay, and Proximity-ligation assay, were employed to identify brain pathological injury and neuroinflammation. To discern the role of Caspase-11 (Casp11) in hematopoietic or non-hematopoietic cells in endotoxemia-induced cognitive decline, bone marrow chimeras were generated through bone marrow transplantation (BMT) using wild-type (WT) and Casp11-deficient mice. In vitro studies involved treating BV2 cells with E. coli-derived outer membrane vesicles to mimic in vivo conditions.

resultsOur findings indicate that the deficiency of Casp11-GSDMD signaling pathways reverses infection-induced cognitive dysfunction. Moreover, cognitive dysfunction can be ameliorated by blocking the IL-1 effect. Mechanistically, the absence of Casp11 signaling significantly mitigated blood‒brain barrier leakage, microglial activation, and synaptic damage in the hippocampal CA3 region, ultimately leading to improved cognitive function.

conclusionThis study unveils the crucial contribution of Casp11 and GSDMD to cognitive impairments and spatial memory loss in a murine sepsis model. Targeting Casp11 signaling emerges as a promising strategy for preventing or treating cognitive dysfunction in patients with severe infections.

Indexed as

CaspasesCaspases, InitiatorCognitive DysfunctionDisease Models, AnimalSignal TransductionAnimalsBlood-Brain BarrierEndotoxemiaGasderminsHippocampusIntracellular Signaling Peptides and ProteinsMaleMiceMice, Inbred C57BLMice, KnockoutPhosphate-Binding ProteinsCasp4 protein, mouseCaspasesCaspases, InitiatorGasderminsGsdmd protein, mouseIntracellular Signaling Peptides and ProteinsPhosphate-Binding ProteinsBlood‒brain barrierCA3Casp11Cognitive dysfunctionEndotoxemiaGSDMDMicrogliaNeuroinflammation

Identifiers

PMID39179968
PMCPMC11342519

What OpenQuestion holds

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LicenceCC BY
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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 OpenQuestion graph.