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

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.