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

作者：Yuxiang Zheng, Wenjie Xu, Zizheng Suo, Yinyin Qu, Lina Lin, Enze Zhang, Dengyang Han, Meikui Wu, Hongyi Li, Hui Zheng, Ting Xiao, Cheng Ni · 发表于：Journal of Neuroinflammation · 年份：2025 · DOI：10.1186/s12974-025-03566-5 · 被引用次数：5 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Intensive Care Unit Cognitive Disorders、Neurological Disease Mechanisms and Treatments

BACKGROUND: 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. METHODS: 18-month-old mice underwent surgery and developed PNCI. The hippocampi of mice in both control and surgery groups were dissected 24 h postoperatively for single-cell RNA sequencing. Immunofluorescence coupled with fluorescence in situ hybridization was used to verify the number of subpopulations and the expression levels of target RNA transcripts in the hippocampus. Cognitive function tests were conducted to evaluate the effects of the TNF inhibitor etanercept in PNCI model. RESULTS: Eight microglial subpopulations and six astrocytic subpopulations were identified in the 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, particu...