Long‐term hippocampal alterations and cognitive impairment in a murine model of surgical sepsis

FEBS Open Bio

卷:16

Research Article

Dong Seong Cho¹  Rebecca Schmitt^2,3  Aneesha Dasgupta^2,3  Alexandra Ducharme¹  Jason Doles^2,3 

[1] Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA

[2] Department of Anatomy, Cell Biology, and Physiology, Indiana University School of Medicine, Indianapolis, USA

[3] Indiana Center for Musculoskeletal Health, Indianapolis, USA

关键词: brain;    cecal ligation and puncture (CLP);    memory;    sepsis‐associated brain dysfunction (SABD);    single‐cell RNA sequencing;   

DOI  :  10.1002/2211-5463.70240

 received in 2025-07-03, accepted in 2026-03-16,  发布年份 2026

来源: Wiley

【 摘 要 】

Cognitive impairment in sepsis survivors is a growing clinical challenge as the number of sepsis cases rise and acute mortality rates fall. It is estimated that up to 70% of sepsis patients experience cognitive dysfunction and many report persistent dysfunction post‐sepsis. Cognitive impairment is a broad term that refers to sepsis‐associated brain dysfunction or encephalopathy (SABD or SAE, respectively). While many contributors, such as inflammation, blood–brain barrier dysfunction, and extended microglial activation are implicated in SABD/SAE development, much is still unknown regarding the underlying mechanistic causes of persistent cognitive defects in sepsis survivors. Here, we employed cecal ligation and puncture (CLP) to model surgical sepsis in mice, after which mice were subjected to multiple memory function assays for up to 2 months post‐sepsis. Furthermore, single‐cell RNA sequencing and validation studies were performed with murine hippocampi to query alterations in the brain microenvironment. Our study shows that CLP mice exhibited decreased spontaneous alternation at 4 weeks and decreases in both short‐ and long‐term recognition (at 6 weeks and 2 weeks, respectively) accompanied by substantially altered cell type makeup of the hippocampus, including hippocampal neuron and pericyte loss. Finally, transcriptional alterations in the macrophage populations implicate aberrant activation in CLP survivors. In conclusion, post‐sepsis mice exhibit reduced memory capacity and altered hippocampal cell composition and transcriptional profiles. This study and associated data set will be valuable for further investigation of the underlying pathophysiology of SABD/SAE and elucidation of potential therapeutic candidates.

【 授权许可】

CC BY   
© 2026 The Author(s). FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

【 图 表 】

Video 1. Mouse retina dissection