ArticleScience advances2023
Microglia mediate neurocognitive deficits by eliminating C1q-tagged synapses in sepsis-associated encephalopathy.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 2 of them syntheses that pooled it.
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The trial behind it
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Who cites it
91 citing papers in PubMed, 2 syntheses or guidelines pooled it, 117 citations in OpenAlex.
- Inflammation and delirium in critically Ill patients: a review.Frontiers in aging neuroscience · 2026Pooled it
- The core role of central nervous system in sepsis-related organ damage.Frontiers in immunology · 2025Pooled it
- Chrysanthemum Morifolium-Derived Nanovesicles Reduce Lactate-Associated Histone Lactylation and Modulate Microglia-Mediated Neuroinflammation in Sepsis-Associated Encephalopathy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Ophthalmic and psychiatric health: the overlooked connection between ocular diseases and mental disorders.Eye (London, England) · 2026Review
- Sevoflurane-induced disruption of critical period Arc signaling drives aberrant microglial synaptic pruning and cognitive deficits.Acta pharmacologica Sinica · 2026Article
- Microglial states revisited: from homeostasis to disease.Nature reviews. Neuroscience · 2026Review
- Early amyloid pathology in mice synergistically worsens post-sepsis behavioral impairment and microglial synaptic phagocytosis.Brain, behavior, & immunity - health · 2026Article
- MAFG as a Redox-Sensitive Node Linking Peripheral Immune Reprogramming to Cognitive Risk in the Sepsis-to-Alzheimer's Disease Continuum: Single-Cell Dissection and Adoptive-Transfer Validation.CNS neuroscience & therapeutics · 2026Article
- Loss of C3 and CD14 reduces region-specific neuroinflammation in a murine polytrauma model.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- A2 astrocyte polarization mediates ketogenic diet protection of blood-central nervous system barriers in experimental autoimmune encephalomyelitis.Neural regeneration research · 2026Article
- Serum C1q as a Novel Predictive Biomarker for Postoperative Delirium After Acute Type A Aortic Dissection.Immunity, inflammation and disease · 2026Article
- The mitophagy-inflammasome axis: a shared pathological hub in Alzheimer's and Parkinson's diseases.Translational neurodegeneration · 2026Review
- Glial-neuronal crosstalk via GABA signaling: mechanistic insights into neuropsychiatric and neurological pathophysiology.Molecular psychiatry · 2026Review
- miR-125b Attenuates Sepsis-Induced Hippocampal Mitochondrial Fission and Cognitive Impairment via the ROS/p53 Pathway.Molecular neurobiology · 2026Article
- Microglia-driven neuroinflammatory signaling in neurodegeneration: mechanisms and therapeutic opportunities.Molecular biology reports · 2026Review
- Research Advances in the Pathogenesis of Sepsis-Associated Encephalopathy.International journal of molecular sciences · 2026Review
- Microglial galectin-3 disrupts parvalbumin interneurons and hippocampal synchrony, driving cognitive deficits.Journal of neuroinflammation · 2026Article
- Clopidogrel, an ADP-P2Y12 Receptor Antagonist, Is Associated With Lower Opioid Consumption and a Reduced Incidence of Delirium in Cancer Patients Receiving Chemotherapy: A Nationwide Retrospective Cohort Study in Japan.Neuropsychopharmacology reports · 2026Article
- Encephalopathy: Cause, Pathogenesis, and Treatment.MedComm · 2026Review
- Microglial state transitions dominate the brain immune response in the subacute phase after cardiac arrest.Journal of neuroinflammation · 2026Article
31 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sepsis-associated encephalopathy (SAE) is a severe and frequent complication of sepsis causing delirium, coma, and long-term cognitive dysfunction. We identified microglia and C1q complement activation in hippocampal autopsy tissue of patients with sepsis and increased C1q-mediated synaptic pruning in a murine polymicrobial sepsis model. Unbiased transcriptomics of hippocampal tissue and isolated microglia derived from septic mice revealed an involvement of the innate immune system, complement activation, and up-regulation of lysosomal pathways during SAE in parallel to neuronal and synaptic damage. Microglial engulfment of C1q-tagged synapses could be prevented by stereotactic intrahippocampal injection of a specific C1q-blocking antibody. Pharmacologically targeting microglia by PLX5622, a CSF1-R inhibitor, reduced C1q levels and the number of C1q-tagged synapses, protected from neuronal damage and synapse loss, and improved neurocognitive outcome. Thus, we identified complement-dependent synaptic pruning by microglia as a crucial pathomechanism for the development of neuronal defects during SAE.
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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 OpenQuestion graph.