ArticleMolecular medicine (Cambridge, Mass.)2012
HMGB1 mediates cognitive impairment in sepsis survivors.
Article in Molecular medicine (Cambridge, Mass.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 130 papers, 3 of them syntheses that pooled it.
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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.
Gut-Brain-axis: Targets for Improvement of Cognition in the Elderly
Integrated Analysis of the Interactions Between Glycemia and Microbiota Composition, and Their Impact on Brain Iron Deposition and Cognition in Subjects With Obesity
Who cites it
130 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Diagnostic and prognostic value of serum S100B in sepsis-associated encephalopathy: A systematic review and meta-analysis.Frontiers in immunology · 2023Pooled it
- What Animal Models Can Tell Us About Long-Term Psychiatric Symptoms in Sepsis Survivors: a Systematic Review.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Pooled it
- Long-Term Cognitive Outcomes After Sepsis: a Translational Systematic Review.Molecular neurobiology · 2019Pooled it
- Trajectories of sepsis survivors in Australia: A scoping review.Journal of the Intensive Care Society · 2026Article
- Effects of Lactate on Improving Cognitive Function and Survival Rate in a Mouse Model of Post-Sepsis Cognitive Impairment.Actas espanolas de psiquiatria · 2026Article
- Optimization of Preclinical Rodent Research Models of Human Shock: Part One Intra-Abdominal Sepsis.Shock (Augusta, Ga.) · 2026Review
- Neuroimmune Mechanisms Transforming Acute Injury to Long-Term Brain Dysfunction After Sepsis.Clinics in chest medicine · 2026Review
- Esketamine ameliorates postoperative cognitive dysfunction aggravated by preoperative acute sleep deprivation in aged mice via the TLR4/NF-κB pathway.Frontiers in aging neuroscience · 2026Article
- Dysregulated neural coding in the vagus nerve during long sepsis.Brain, behavior, & immunity - health · 2025Article
- Clinical and biochemical assessments of circulating High Mobility Group Box Protein1 in children with epilepsy: relation to cognitive function and drug responsiveness.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Article
- Sepsis-Associated Brain Dysfunction: Mechanisms, Clinical Insights, and Therapeutic Strategies.Current drug targets · 2025Review
- Sepsis-associated encephalopathy: Mechanisms, Diagnosis, and Treatments update.International journal of biological sciences · 2025Review
- The Biological Changes of Synaptic Plasticity in the Pathological Process of Sepsis-associated Encephalopathy.Current neuropharmacology · 2025Review
- Brain imaging and machine learning reveal uncoupled functional network for contextual threat memory in long sepsis.Scientific reports · 2024Article
- ADAR1 prevents ZBP1-dependent PANoptosis via A-to-I RNA editing in developmental sevoflurane neurotoxicity.Cell biology and toxicology · 2024Article
- Lupus autoantibodies initiate neuroinflammation sustained by continuous HMGB1:RAGE signaling and reversed by increased LAIR-1 expression.Nature immunology · 2024Article
- High Mobility Group Box 1 Levels as an Inflammatory Mediator in Bipolar Mania.Noro psikiyatri arsivi · 2024Article
- Post-translational modifications in sepsis-induced organ dysfunction: mechanisms and implications.Frontiers in immunology · 2024Review
- Corticosteroid Treatment During Sepsis Alters Hippocampal Function in Male and Female Survivors.Biological psychiatry global open science · 2024Article
- Systemic inflammation, neuroinflammation and perioperative neurocognitive disorders.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
70 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors.
Funding
Abstract
Severe sepsis, a syndrome that complicates infection and injury, affects 750,000 annually in the United States. The acute mortality rate is approximately 30%, but, strikingly, sepsis survivors have a significant disability burden: up to 25% of survivors are cognitively and physically impaired. To investigate the mechanisms underlying persistent cognitive impairment in sepsis survivors, here we developed a murine model of severe sepsis survivors following cecal ligation and puncture (CLP) to study cognitive impairments. We observed that serum levels of high mobility group box 1 (HMGB1), a critical mediator of acute sepsis pathophysiology, are increased in sepsis survivors. Significantly, these levels remain elevated for at least 4 wks after CLP. Sepsis survivors develop significant, persistent impairments in learning and memory, and anatomic changes in the hippocampus associated with a loss of synaptic plasticity. Administration of neutralizing anti-HMGB1 antibody to survivors, beginning 1 wk after onset of peritonitis, significantly improved memory impairments and brain pathology. Administration of recombinant HMGB1 to naïve mice recapitulated the memory impairments. Together, these findings indicate that elevated HMGB1 levels mediate cognitive decline in sepsis survivors, and suggest that it may be possible to prevent or reverse cognitive impairments in sepsis survivors by administration of anti-HMGB1 antibodies.
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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.