ArticleThe Journal of clinical investigation2019
Circulating heparan sulfate fragments mediate septic cognitive dysfunction.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 1 of them a synthesis 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.
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Who cites it
88 citing papers in PubMed, 1 synthesis or guideline pooled it, 114 citations in OpenAlex.
- Pooled it
- Effects of an early restrictive versus liberal fluid strategy on long-term patient-centered outcomes in sepsis-induced hypotension: an open-label, randomized controlled trial.American journal of respiratory and critical care medicine · 2026Trial
- Endothelial Glycocalyx Degradation in Sepsis: Analysis of the Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS) Trial, a Multicenter, Phase 3, Randomized Trial.Annals of the American Thoracic Society · 2025Trial
- Lung endothelial cytopathic tau is sufficient to impair long-term potentiation during infection.American journal of respiratory cell and molecular biology · 2026Article
- Measuring health-related quality of life in sepsis survivors and caregivers: a mapping review and a preliminary conceptual framework.Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation · 2026Review
- Plasma Heparan Sulfate Structural Variation and Phenotypic Heterogeneity in Pediatric Acute Respiratory Distress Syndrome.Research square · 2026Article
- Barrier breakdown: lung-brain crosstalk in systemic inflammation.Journal of neuroinflammation · 2026Review
- Glycoinformatic Profiling of Label-Free Intact Heparan Sulfate Oligosaccharides.Molecular & cellular proteomics : MCP · 2026Article
- Neuroimmune Mechanisms Transforming Acute Injury to Long-Term Brain Dysfunction After Sepsis.Clinics in chest medicine · 2026Review
- Endothelial Glycocalyx Degradation as a Mediator of Neuroinflammation and Cognitive Impairment in Aged Rats: Protective Role of SS-31.Molecular neurobiology · 2025Article
- Persistent Subclinical Inflammation and Long-term Functional and Cognitive Outcomes After Dengue Shock and Septic Shock in Vietnam.Open forum infectious diseases · 2025Article
- Beyond the Hit: Muscle and Vascular Tissue Responses to Contact Exposure in Collision Sports-A Narrative Review.Sports medicine (Auckland, N.Z.) · 2025Review
- Mechanisms of lung crosstalk with end organs: scientific session V-ReSPIRE 2025.American journal of physiology. Lung cellular and molecular physiology · 2025Review
- Applications of Surface Plasmon Resonance in Heparan Sulfate Interactome Research.Biomedicines · 2025Review
- Editor's Choice Development of a method to measure the activity of heparan sulfate 6-endosulfatase for biological research.Glycobiology · 2025Article
- Postoperative sepsis and its sequential impact on dementia.Critical care (London, England) · 2025Article
- Vitamin C for sepsis: from mechanisms to individualized therapy.Frontiers in medicine · 2025Review
- Targeting synaptic plasticity to bridge translational gaps in sepsis-associated encephalopathy.Frontiers in aging neuroscience · 2025Review
- Sepsis-associated encephalopathy: Mechanisms, Diagnosis, and Treatments update.International journal of biological sciences · 2025Review
- Targeted rescue of synaptic plasticity improves cognitive decline in sepsis-associated encephalopathy.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
28 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 1 country.
Funding
Abstract
Septic patients frequently develop cognitive impairment that persists beyond hospital discharge. The impact of sepsis on electrophysiological and molecular determinants of learning is underexplored. We observed that mice that survived sepsis or endotoxemia experienced loss of hippocampal long-term potentiation (LTP), a brain-derived neurotrophic factor-mediated (BDNF-mediated) process responsible for spatial memory formation. Memory impairment occurred despite preserved hippocampal BDNF content and could be reversed by stimulation of BDNF signaling, suggesting the presence of a local BDNF inhibitor. Sepsis is associated with degradation of the endothelial glycocalyx, releasing heparan sulfate fragments (of sufficient size and sulfation to bind BDNF) into the circulation. Heparan sulfate fragments penetrated the hippocampal blood-brain barrier during sepsis and inhibited BDNF-mediated LTP. Glycoarray approaches demonstrated that the avidity of heparan sulfate for BDNF increased with sulfation at the 2-O position of iduronic acid and the N position of glucosamine. Circulating heparan sulfate in endotoxemic mice and septic humans was enriched in 2-O- and N-sulfated disaccharides; furthermore, the presence of these sulfation patterns in the plasma of septic patients at intensive care unit (ICU) admission predicted persistent cognitive impairment 14 days after ICU discharge or at hospital discharge. Our findings indicate that circulating 2-O- and N-sulfated heparan sulfate fragments contribute to septic cognitive impairment.
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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.