Evidence map›Paper›PMID 41307757›Full record

ArticleNeuromolecular medicine2025

Comparative Hippocampal Transcriptomics Reveals Model-Specific Pathways and Convergent Inflammation in Sepsis-Associated Encephalopathy.

Xueling Zhang, Mengshi Yang, Yaxuan Zhang, Limin Tao, Xiyu Chen, Fei Liu, Bin Zhang, Guangzhi Shi

Abstract readComparative Study
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Article in Neuromolecular medicine, 2025. 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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5 · Who and what money

Authors and funding

8 authors.

Xueling ZhangDepartment of Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Mengshi YangDepartment of Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Yaxuan ZhangDepartment of Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Limin TaoDepartment of Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Xiyu ChenDepartment of Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Fei LiuDepartment of Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Bin ZhangDepartment of Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. victorbin922@163.com.
Guangzhi ShiDepartment of Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. shiguangzhi@bjtth.org.

Funding

Beijing Science and Technology Planning Project Z201100005520039
6 · The paper itself

Abstract

Sepsis-associated encephalopathy (SAE) is a serious sepsis complication with high mortality. Animal models, including cecal ligation and puncture (CLP), lipopolysaccharide (LPS) injection, and peritoneal contamination and infection (PCI), are known to trigger distinct inflammatory responses with differential hippocampal impact. This study aimed to comprehensively compare the hippocampal transcriptomic profiles and validate key findings through independent experimentation. Transcriptomic datasets GSE253309 (CLP), GSE226120 (LPS), and GSE167610 (PCI) were retrieved from the GEO database. Bioinformatics analyses were employed to identify DEGs and enriched pathways. WGCNA pinpointed characteristic modules, and PPI networks were constructed and analyzed. Critically, an independent CLP-induced SAE mouse model was established, and hippocampal RNA sequencing was performed for confirmation. DEG analysis revealed 381, 533, and 85 significant DEGs in the CLP, LPS, and PCI datasets, respectively. CLP and LPS models shared a robust signature of neuroinflammation, significantly enriching GO terms related to immune response and inflammatory response, and KEGG pathways such as TNF, NF-κB, IL-17. In stark contrast, the PCI model was predominantly associated with cell migration, aldarate metabolism, and enriched in metabolic pathways, including bile secretion, ascorbate and aldarate metabolism. Cross-dataset analysis identified 29 common DEGs, from which a PPI network of 16 hub genes was constructed. Importantly, independent validation confirmed a strong concordance (r = 0.576) between the CLP-seq discovery cohort and the experimental CLP-seq data. Lcn2, S100a8, S100a9, Lrg1 and the TNF/IL-17 signaling pathways were robustly verified. CLP and LPS models demonstrate convergent hippocampal transcriptomic profiles distinct from PCI. Lcn2, S100a8, S100a9, Lrg1 and the TNF and IL-17 signaling pathways are highly reliable core features in SAE.

Indexed as

HippocampusNeuroinflammatory DiseasesSepsis-Associated EncephalopathyTranscriptomeAnimalsCecumComputational BiologyDatabases, GeneticDisease Models, AnimalGene Expression ProfilingGene Regulatory NetworksHumansInflammationLigationLipopolysaccharidesMaleLipopolysaccharidesCecal ligation and punctureLipopolysaccharidePeritoneal contamination and infectionSepsis-associated encephalopathySignal pathwaysTranscriptome

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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.