ArticleJournal of neuroinflammation2020
Sustained hyperammonemia induces TNF-a IN Purkinje neurons by activating the TNFR1-NF-κB pathway.
Article in Journal of neuroinflammation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 45 citations in OpenAlex.
- Peripheral IL-17 Triggers, and anti-IL-17 Treatment Prevents, Neuroinflammation and Alterations in Neurotransmission in Hippocampus and Cognitive Impairment in Hyperammonemic Rats.Molecular neurobiology · 2026Article
- The role of ammonia in chronic liver disease.Hepatology communications · 2026Review
- Extracellular vesicles from plasma of patients with minimal hepatic encephalopathy induce neuroinflammation and cognitive impairment in rats, which are prevented by treating the patients with rifaximin.Journal of neuroinflammation · 2026Article
- Neuronal UBE3A loss engages a TNF-driven neuron-to-microglia axis that promotes synapse remodeling.bioRxiv : the preprint server for biology · 2026Article
- Pretreatment of trans-ferulic acid improved neurotoxicity in a thioacetamide-induced hepatic encephalopathy rat model; participation of the MAPK/NF-κb signaling pathway.Frontiers in pharmacology · 2026Article
- Regulating the crosstalk betweenFrontiers in immunology · 2026Review
- Blood-brain barrier dysfunction in hepatic encephalopathy: pathophysiology, diagnostic assessment and therapeutic perspectives.Metabolic brain disease · 2025Review
- Feedback regulation of VISTA and Treg by TNF-α controls T cell responses in drug allergy.Allergy · 2025Article
- Article
- Hyperammonemia increases the release of pathological extracellular vesicles from monocytes by impairing lysosomal function and autophagy through the TNFα-cAMP-PKA-LC3 pathway.Frontiers in immunology · 2025Article
- Neuronal injury and hepatotoxicity: astrocytes and stellate cells convergence and their role in tissue repair.Frontiers in neuroscience · 2025Review
- A transient blood IL-17 increase triggers neuroinflammation in cerebellum and motor incoordination in hyperammonemic rats.Journal of neuroinflammation · 2024Article
- Extracellular Vesicles from Mesenchymal Stem Cells Reverse Neuroinflammation and Restore Motor Coordination in Hyperammonemic Rats.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Article
- Review
- The Roles of RhoA/ROCK/NF-κB Pathway in Microglia Polarization Following Ischemic Stroke.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Review
- Increased levels and activation of the IL-17 receptor in microglia contribute to enhanced neuroinflammation in cerebellum of hyperammonemic rats.Biological research · 2024Article
- NF-κB in biology and targeted therapy: new insights and translational implications.Signal transduction and targeted therapy · 2024Review
- Selenium Deficiency Causes Iron Death and Inflammatory Injury Through Oxidative Stress in the Mice Gastric Mucosa.Biological trace element research · 2024Article
- Simvastatin Significantly Reduced Alcohol-Induced Cardiac Damage in Adolescent Mice.Cardiovascular toxicology · 2024Article
- Neuroinflammation alters GABAergic neurotransmission in hyperammonemia and hepatic encephalopathy, leading to motor incoordination. Mechanisms and therapeutic implications.Frontiers in pharmacology · 2024Review
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundPatients with liver cirrhosis may develop hepatic encephalopathy. Rats with chronic hyperammonemia exhibit neurological alterations mediated by peripheral inflammation and neuroinflammation. Motor incoordination is due to increased TNF-a levels and activation of its receptor TNFR1 in the cerebellum. The aims were to assess (a) whether peripheral inflammation is responsible for TNF-a induction in hyperammonemic rats, (b) the cell type(s) in which TNF-a is increased, (c) whether this increase is associated with increased nuclear NF-κB and TNFR1 activation, (d) the time course of TNF-a induction, and (e) if TNF-a is induced in the Purkinje neurons of patients who die with liver cirrhosis.
methodsWe analyzed the level of TNF-a mRNA and NF-κB in microglia, astrocytes, and Purkinje neurons in the cerebellum after 1, 2, and 4 weeks of hyperammonemia. We assessed whether preventing peripheral inflammation by administering an anti-TNF-a antibody prevents TNF-a induction. We tested whether TNF-a induction is reversed by R7050, which inhibits the TNFR1-NF-κB pathway, in ex vivo cerebellar slices.
resultsHyperammonemia induced microglial and astrocyte activation at 1 week. This was followed by TNF-a induction in both glial cell types at 2 weeks and in Purkinje neurons at 4 weeks. The level of TNF-a mRNA increased in parallel with the TNF-a protein level, indicating that TNF-a was synthesized in Purkinje cells. This increase was associated with increased NF-κB nuclear translocation. The nuclear translocation of NF-κB and the increase in TNF-a were reversed by R7050, indicating that they were mediated by the activation of TNFR1. Preventing peripheral inflammation with an anti-TNF-a antibody prevents TNF-a induction.
conclusionSustained (4 weeks) but not short-term hyperammonemia induces TNF-a in Purkinje neurons in rats. This is mediated by peripheral inflammation. TNF-a is also increased in the Purkinje neurons of patients who die with liver cirrhosis. The results suggest that hyperammonemia induces TNF-a in glial cells and that TNF-a released by glial cells activates TNFR1 in Purkinje neurons, leading to NF-κB nuclear translocation and the induction of TNF-a expression, which may contribute to the neurological alterations observed in hyperammonemia and hepatic encephalopathy.
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