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It is estimated that up to 70% of sepsis patients experience cognitive dysfunction and many report persistent dysfunction post\u2010sepsis. Cognitive impairment is a broad term that refers to sepsis\u2010associated brain dysfunction or encephalopathy (SABD or SAE, respectively). While many contributors, such as inflammation, blood\u2013brain 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\u2010sepsis. Furthermore, single\u2010cell 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\u2009weeks and decreases in both short\u2010 and long\u2010term recognition (at 6\u2009weeks and 2\u2009weeks, 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\u2010sepsis 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.<\/jats:p>","DOI":"10.1002\/2211-5463.70240","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T04:17:14Z","timestamp":1776399434000},"page":"1657-1668","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Long\u2010term hippocampal alterations and cognitive impairment in a murine model of surgical sepsis"],"prefix":"10.1002","volume":"16","author":[{"given":"Dong Seong","family":"Cho","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Mayo Clinic  Rochester Minnesota 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