老年大鼠海马体神经炎症和脑血管内皮细胞的单细胞转录组学

Single-cell transcriptomics of neuroinflammation and cerebrovascular endothelial cells in the aged rat hippocampus.

作者信息

Liu Fangyan, Fu Huiqun, Li Zhongjia, Wu Yan, Wang Tianlong

机构信息

Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, 45 Changchun Street, Xicheng District, Beijing 100053, China.

Beijing Key Laboratory of Neural Regeneration and Repair, Department of Anatomy, School of Basic Medical Sciences, Beijing Institute of Brain Disorders, Capital Medical University, Beijing 100069, China.

出版信息

iScience. 2025 Aug 11;28(9):113332. doi: 10.1016/j.isci.2025.113332. eCollection 2025 Sep 19.

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). 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.

围手术期神经认知障碍（PNDs）在老年人中很常见，海马神经炎症在其发病机制中起关键作用。为了描绘神经炎症的细胞图谱，我们对全身注射脂多糖（LPS）后第3天的老年大鼠海马细胞进行了单细胞RNA测序（scRNA-seq）。我们在小胶质细胞、浸润性免疫细胞，尤其是脑血管内皮细胞（ECs）中发现了明显的转录组改变。内皮细胞表现出显著的氧化应激相关变化，包括DNA损伤诱导转录本4（REDD1）的上调。REDD1基因敲低可减轻氧化应激并促进内皮细胞存活。我们的研究结果提供了一张老年海马神经炎症微环境的高分辨率图谱，并强调了内皮细胞功能障碍、血脑屏障（BBB）破坏和免疫浸润在PNDs相关病理学中的作用。