ArticleNature communications2024
Adenosine triggers early astrocyte reactivity that provokes microglial responses and drives the pathogenesis of sepsis-associated encephalopathy in mice.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 46 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
46 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Natural antidepressants in neuroimmunomodulation: molecular mechanisms, action targets, and therapeutic potential.Frontiers in immunology · 2025Pooled it
- A multistage micro-nano biosystem prevents sepsis-associated encephalopathy through coordinated neuroinflammation suppression and gut-brain axis modulation.Bioactive materials · 2026Article
- Adenosine receptor signaling in vascular diseases: from molecular mechanisms to targeted therapeutics.Acta pharmacologica Sinica · 2026Review
- SIRT1 Activation Ameliorates Neuroinflammation and Cognitive Impairment in a Murine SAE Model and is Associated with the Nrf2/GPX4 Pathway.Neurochemical research · 2026Article
- From Iron to Depression: The Crosstalk Between the Periphery and Brain.Neuroscience bulletin · 2026Review
- M2 microglial exosomal miR-1949 ameliorates sepsis-associated encephalopathy through DKK1/Wnt/β-catenin-mediated microglial repolarization.Archives of pharmacal research · 2026Article
- Recombinant Human Thymosin β4 Attenuates Endotoxemia-Induced ALI and EAE by Suppressing Inflammatory and Oxidative Responses.Biomolecules · 2026Article
- Emerging Roles of Adenosine Metabolism in Astrocytes During Brain Injury.CNS neuroscience & therapeutics · 2026Review
- Review
- Endothelial-specific Ezh2 deficiency exacerbates blood-brain barrier dysfunction and neuroinflammation in sepsis-associated encephalopathy.Journal of neuroinflammation · 2026Article
- Article
- Environmental pollutants and autism spectrum disorder: Effects of plasticizers on core phenotypes and molecular targets.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Astrocyte States in Brain Aging and Neurodegeneration: At the Crossroads of Senescence and Reactivity.Neurochemical research · 2026Review
- Postoperative neurocognitive disorder: migration and crosstalk of inflammation in the peripheral and central nervous system.Perioperative medicine (London, England) · 2026Review
- Astrocyte-blood-brain barrier crosstalk in cerebral small vessel disease: linking barrier dysfunction to neurovascular failure.Frontiers in neurology · 2026Review
- A Lipid Road to Neuroimmunology: Fatty Acids Linking Immune and Nervous Systems.Neuroimmunomodulation · 2026Review
- Gut microbiota dysbiosis in sepsis and sepsis-associated organ injury: mechanisms, gut-organ axes, and therapeutic strategies.Frontiers in microbiology · 2026Review
- Metabolic reprogramming in sepsis-associated encephalopathy: emerging mechanisms, candidate biomarkers, and future therapeutic directions.Frontiers in medicine · 2026Review
- USP11-PGAM5 Axis Promotes Neurotoxic Astrocyte Reactivity by Aggravating the mtDNA-cGAS-STING Pathway After Intracerebral Hemorrhage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Hyperbaric oxygen therapy in sepsis-associated encephalopathy: pathophysiological rationale, preclinical evidence, and translational challenges.Frontiers in cellular neuroscience · 2026Review
Corrections and comments
- Erratum issued
Authors and funding
15 authors.
Funding
Abstract
Molecular pathways mediating systemic inflammation entering the brain parenchyma to induce sepsis-associated encephalopathy (SAE) remain elusive. Here, we report that in mice during the first 6 hours of peripheral lipopolysaccharide (LPS)-evoked systemic inflammation (6 hpi), the plasma level of adenosine quickly increased and enhanced the tone of central extracellular adenosine which then provoked neuroinflammation by triggering early astrocyte reactivity. Specific ablation of astrocytic Gi protein-coupled A1 adenosine receptors (A1ARs) prevented this early reactivity and reduced the levels of inflammatory factors (e.g., CCL2, CCL5, and CXCL1) in astrocytes, thereby alleviating microglial reaction, ameliorating blood-brain barrier disruption, peripheral immune cell infiltration, neuronal dysfunction, and depression-like behaviour in the mice. Chemogenetic stimulation of Gi signaling in A1AR-deficent astrocytes at 2 and 4 hpi of LPS injection could restore neuroinflammation and depression-like behaviour, highlighting astrocytes rather than microglia as early drivers of neuroinflammation. Our results identify early astrocyte reactivity towards peripheral and central levels of adenosine as an important pathway driving SAE and highlight the potential of targeting A1ARs for therapeutic intervention.
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What 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.