ReviewBiochemical pharmacology2010
Glutamine as a mediator of ammonia neurotoxicity: A critical appraisal.
Review in Biochemical pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
65 citing papers in PubMed, 148 citations in OpenAlex.
- Pharmacokinetics/pharmacodynamics of L-ornithine phenylacetate in overt hepatic encephalopathy and the effect of plasma ammonia concentration reduction on clinical outcomes.Clinical and translational science · 2022Trial
- Quantitative CT-scan to evaluate cerebral edema secondary to hyperammonemia in ICU: A proof-of-concept study.Journal of intensive medicine · 2026Article
- Pre-emptive treatment in later-onset urea cycle disorders: a clinical perspective on glycerol phenylbutyrate.Orphanet journal of rare diseases · 2026Review
- Mechanistic Integration of Beta-Alanine-Carnosine Buffering and Glutamine Metabolism in Exercise-Induced Muscle-Brain Crosstalk: Implications for Aging, Neurodegeneration, and Cognitive Decline.Molecular neurobiology · 2026Review
- Modeling Release Scaffolds for Spinal Cord Tissue Regeneration After Injury Using COMSOL Simulation.Nanomaterials (Basel, Switzerland) · 2026Article
- Glutamine and Albumin Levels in Cerebrospinal Fluid Are Correlated with Neurological Severity in an Experimental Model of Acute Hepatic Encephalopathy.Metabolites · 2025Article
- Bioelectrosynthesis of Signaling Molecules for Selective Modulation of Cell Signaling.Angewandte Chemie (International ed. in English) · 2025Article
- Hyperammonaemia in Dogs Presenting with Acute Epileptic Seizures-More than Portosystemic Shunts.Animals : an open access journal from MDPI · 2025Article
- Regulation of L-Lactate in Glutamate Excitotoxicity Under Cerebral Ischemia: Pathophysiology and Preventive Strategy.Pharmaceuticals (Basel, Switzerland) · 2025Review
- GLS2 reduces the occurrence of epilepsy by affecting mitophagy function in mouse hippocampal neurons.CNS neuroscience & therapeutics · 2024Article
- Article
- Amino Acid Transporters Proteins Involved in the Glutamate-Glutamine Cycle and Their Alterations in Murine Models of Alzheimer's Disease.Molecular neurobiology · 2024Review
- Digestive dynamics: Unveiling interplay between the gut microbiota and the liver in macronutrient metabolism and hepatic metabolic health.Physiological reports · 2024Review
- Mitochondrial Changes in Rat Brain Endothelial Cells Associated with Hepatic Encephalopathy: Relation to the Blood-Brain Barrier Dysfunction.Neurochemical research · 2024Review
- Review
- Potential Defence Mechanisms Triggered by Monosodium Glutamate Sub-Chronic Consumption in Two-Year-Old Wistar Rats.Nutrients · 2023Article
- Metabolites Alterations and Liver Injury in Hepatic Encephalopathy Models Evaluated by Use of 7T-MRI.Metabolites · 2022Article
- Side effects of amino acid supplements.Physiological research · 2022Article
- The Role of Vti1a in Biological Functions and Its Possible Role in Nervous System Disorders.Frontiers in molecular neuroscience · 2022Review
- The Role of Nrf2 Transcription Factor and Sp1-Nrf2 Protein Complex in Glutamine Transporter SN1 Regulation in Mouse Cortical Astrocytes Exposed to Ammonia.International journal of molecular sciences · 2021Article
5 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
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Ammonia is a major neurotoxin implicated in hepatic encephalopathy (HE). Here we discuss evidence that many aspects of ammonia toxicity in HE-affected brain are mediated by glutamine (Gln), synthesized in excess from ammonia and glutamate by glutamine synthetase (GS), an astrocytic enzyme. The degree to which Gln is increased in brains of patients with HE was found to positively correlate with the grade of HE. In animals with HE, a GS inhibitor, methionine sulfoximine (MSO), reversed a spectrum of manifestations of ammonia toxicity, including brain edema and increased intracranial pressure, even though MSO itself increased brain ammonia levels. MSO inhibited, while incubation with Gln reproduced the oxidative stress and cell swelling observed in ammonia-exposed cultured astrocytes. Recent studies have shown that astrocytes swell subsequent to Gln transport into mitochondria and its degradation back to ammonia, which then generates reactive oxygen species and the mitochondrial permeability transition. This sequence of events led to the formulation of the "Trojan Horse" hypothesis. Further verification of the role of Gln in the pathogenesis of HE will have to account for: (1) modification of the effects of Gln by interaction of astrocytes with other CNS cells; and (2) direct effects of Gln on these cells. Recent studies have demonstrated a "Trojan Horse"-like effect of Gln in microglia, as well as an interference by Gln with the activation of the NMDA/NO/cGMP pathway by ammonia as measured in whole brain, a process that likely also involves neurons.
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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.