Single-cell transcriptomic profiling reveals endothelial oxidative stress and REDD1 upregulation in aged rat hippocampi, highlighting vascular dysfunction in neurocognitive disorders.
Summary 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.
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Liu et al. (2025) studied this question.
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