Single-nucleus transcriptomics reveals sepsis-related neurovascular dysfunction in the human hippocampus.

ABSTRACT:

Introduction

Sepsis is increasingly recognized as a major precipitant of long-term cognitive impairment, yet the cellular mechanisms underlying hippocampal vulnerability remain elusive.

Methods

We performed single-nucleus RNA sequencing of human hippocampal tissues from sepsis and control patients to profile neurovascular cell populations and their transcriptional changes.

Results

We identified profound neurovascular alterations involving 21 distinct cell populations. Astrocytes and microglia exhibited marked polarization: Astrocyte 2 showed simultaneous upregulation of neurotoxic A1 and neuroprotective A2 gene signatures in sepsis, whereas Astrocyte 1 displayed reduced A1 activity and a relatively quiescent profile. Microglia 2 demonstrated a prominent M1-like inflam

SUBMITTER: Liu L 

PROVIDER: S-EPMC12477015 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature