Perioperative neurocognitive disorders (PNDs) are common in the elderly, with hippocampal neuroinflammation playing a key role in their pathogenesis. To characterize the cellular landscape of neuroinflammation, we performed single-cell RNA sequencing (scRNA-seq) of hippocampal cells from aged rats on day 3 after systemic lipopolysaccharide (LPS) injection. We identified distinct transcriptomic alterations in microglia, infiltrating immune cells, and notably cerebrovascular endothelial cells (ECs). ECs exhibited prominent oxidative stress-related changes, including the upregulation of DNA-damage-inducible transcript 4 (REDD1). In vitro REDD1 knockdown alleviated oxidative stress and promoted ECs survival. Our findings offer a high-resolution map of the neuroinflammatory microenvironment in the aged hippocampus and underscore the role of ECs dysfunction, blood-brain barrier (BBB) disruption, and immune infiltration in PNDs-related pathology.
基金：
Beijing Municipal Health Commission of China [Jing2019-2]; Post-subsidy funds for National Clinical Research Center, Ministry of Science and Technology (China) of China [303-01-001-0272-03]
第一作者机构：[1]Capital Med Univ, Xuanwu Hosp, Dept Anesthesiol, 45 Changchun St, Beijing 100053, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Capital Med Univ, Xuanwu Hosp, Dept Anesthesiol, 45 Changchun St, Beijing 100053, Peoples R China[3]Natl Clin Res Ctr Geriatr Dis, Beijing, Peoples R China[4]Capital Med Univ, Beijing Inst Brain Disorders, Ctr Sleep & Consciousness Disorders, Collaborat Innovat Ctr Brain Disorders, Beijing, Peoples R China
推荐引用方式(GB/T 7714)：
Liu Fangyan,Fu Huiqun,Li Zhongjia,et al.Single-cell transcriptomics of neuroinflammation and cerebrovascular endothelial cells in the aged rat hippocampus[J].ISCIENCE.2025,28(9):doi:10.1016/j.isci.2025.113332.
APA：
Liu, Fangyan,Fu, Huiqun,Li, Zhongjia,Wu, Yan&Wang, Tianlong.(2025).Single-cell transcriptomics of neuroinflammation and cerebrovascular endothelial cells in the aged rat hippocampus.ISCIENCE,28,(9)
MLA：
Liu, Fangyan,et al."Single-cell transcriptomics of neuroinflammation and cerebrovascular endothelial cells in the aged rat hippocampus".ISCIENCE 28..9(2025)
