ArticleMolecular psychiatry2025
Targeting complement C3/C3aR pathway restores rejuvenation factor PF4 and mitigates neurocognitive impairments in age-related perioperative neurocognitive disorders.
Article in Molecular psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Regulatory T cells in perioperative neurocognitive disorders: a systematic review with structured narrative synthesis from molecular mechanisms to clinical translation.Frontiers in molecular neuroscience · 2026Pooled it
- Microglia and neuroinflammation: function, heterogeneity, and crosstalk.Cellular & molecular immunology · 2026Review
- Association between age and postoperative delirium after hip or knee replacement: a secondary analysis of a publicly available dataset.BMC anesthesiology · 2026Article
- Microglial galectin-3 disrupts parvalbumin interneurons and hippocampal synchrony, driving cognitive deficits.Journal of neuroinflammation · 2026Article
- From Bench to Bedside: New Frontiers in Understanding and Treating Postoperative Delirium.Journal of clinical medicine · 2025Review
- PF4 at the Crossroads of Immunity and Neurodegeneration: A New Window Into Brain Aging.CNS neuroscience & therapeutics · 2025Article
- Review
Corrections and comments
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Authors and funding
22 authors.
Funding
Abstract
Perioperative neurocognitive disorders (PND), including postoperative delirium (POD), delayed neurocognitive recovery (dNCR) and postoperative neurocognitive disorder (PNCD), affect up to 10% of surgical patients older than 60 years, and currently there are no effective therapies to prevent PND. The gut microbiota is linked to PND through the gut-brain axis, promoting neuroinflammation via activation and proliferation of microglia and astrocytes in the central nervous system (CNS). In this study, we show that perioperative use of ceftriaxone, a long-acting β-lactam antibiotic, can prevent the development of PND in elderly surgical patients. This effect is associated with reduced serum complement C3 levels and increased levels of platelet factor 4 (PF4). Using an aged mouse model of PND, we found that C3/C3aR axis mediated the interaction of astroglia and microglia during the early stages of neuroinflammation. Genetic ablation or pharmacological blockade of C3/C3aR signaling pathway suppressed neuroinflammation and attenuated cognitive declines in PND. The C3/C3aR axis is essential for surgery-induced platelet count and circulating PF4 declines, and mice supplemented with recombinant PF4 exhibited reduced neuroinflammation and improved cognitive function. Together, our findings revealed the new roles of the C3/C3aR signaling pathway in platelet dysfunction and neuroinflammation in age-related PND, and these results highlight new potential therapeutic strategies for PND.
Indexed as
Identifiers
40659841What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.