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Inflammation associated microglial expansion disrupts hippocampal glial network communication, driving postoperative neurocognitive impairment

ABSTRACT: Postoperative neurocognitive impairment (PNCI) significantly affects the recovery and long-term outcomes of elderly patients, with central nervous system (CNS) inflammation serving as the key pathogenic driver of its development. As the resident immune cells of the CNS, microglia play a crucial role in regulating perioperative inflammation and maintaining homeostasis. However, the contribution, phenotypic heterogeneity, and communication network of perioperative microglia in the development of PNCI remain insufficiently characterized. In this study, 18-month-old mice underwent surgery and developed PNCI. Single-cell RNA sequencing was performed, which identified eight microglial subpopulations and six astrocytic subpopulations in hippocampus. Postoperatively, the percentage of microglial subpopulations underwent dramatic changes, with inflammation associated microglia (IAM) increasing more than 14-fold and transition state microglia (TSM) increasing more than 33-fold. These alterations were accompanied by a marked enhancement of intercellular communications among glial cells, particularly driven by the activation of TNF signaling pathway in IAM. This pathway, along with its associated regulatory network, critically modulated the function of astrocytes and endothelial cells, thereby playing a pivotal role in CNS inflammation and the subsequent development of PNCI. Notably, administration of TNF inhibitor etanercept attenuated IAM activation and glial network communication in the hippocampus, which was associated with improved cognitive performance in PNCI mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE289098 | GEO | 2025/11/02

REPOSITORIES: GEO

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Inflammation associated microglial expansion disrupts hippocampal glial network communication, driving postoperative neurocognitive impairment

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