ReviewMetabolic brain disease2014
Cerebral effects of ammonia in liver disease: current hypotheses.
Review in Metabolic brain disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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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
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.
- Comparison of probiotics to lactulose for minimal hepatic encephalopathy in patients with cirrhosis: a meta-analysis of randomized controlled trials.Frontiers in medicine · 2026Pooled it
- Diagnostics of Inherited Metabolic Diseases in Newborns with the Hyperammonemia Syndrome at the Onset of Disease (Pilot Study).Sovremennye tekhnologii v meditsine · 2021Trial
- Which of the branched-chain amino acids increases cerebral blood flow in hepatic encephalopathy? A double-blind randomized trial.NeuroImage. Clinical · 2018Trial
- Cerebrovascular, cardiovascular and strength responses to acute ammonia inhalation.European journal of applied physiology · 2016Trial
- Guanosine Attenuates Astrocyte-Associated Glutamatergic Dysregulation and Improves Survival in Acute Liver Failure-Induced Hepatic Encephalopathy.Metabolites · 2026Article
- Brain magnetic resonance imaging findings in hyperammonemic hepatic encephalopathy: A case series and literature review.Biomedical reports · 2025Article
- Chemotactic Zn micromotor for treatment of high blood ammonia-associated hepatic encephalopathy.Nature communications · 2025Article
- Bile duct ligation-induced cirrhosis does not alter the blood-brain barrier permeability to sucrose in rats.Metabolic brain disease · 2024Article
- Development of a Polymersome Blood Ammonia Assay Coupled with a Portable Near-Infrared Fluorometer.ACS bio & med chem Au · 2024Article
- Optimized Ammonia-Sensing Electrode with CeONanomaterials (Basel, Switzerland) · 2024Article
- Paper-based colorimetric hyperammonemia sensing by controlled oxidation of plasmonic silver nanoparticles.Nanoscale advances · 2024Article
- The Metabolic Impact of Nonalcoholic Fatty Liver Disease on Cognitive Dysfunction: A Comprehensive Clinical and Pathophysiological Review.International journal of molecular sciences · 2024Review
- Flaxseed Oil (Nutrients · 2023Article
- Hyperammonemia in Inherited Metabolic Diseases.Cellular and molecular neurobiology · 2022Review
- Liver transplantation in rare late-onset ornithine transcarbamylase deficiency with central nervous system injury: A case report and review of the literature.Brain and behavior · 2022Review
- Secondary Dysfunction of the Intestinal Barrier in the Pathogenesis of Complications of Acute Poisoning.Journal of evolutionary biochemistry and physiology · 2022Article
- N-acetylaspartate release by glutaminolytic ovarian cancer cells sustains protumoral macrophages.EMBO reports · 2021Article
- γδ T cells in malaria: a double-edged sword.The FEBS journal · 2021Review
- Treatment of Hyperammonemia by Transplanting a Symbiotic Pair of Intestinal Microbes.Frontiers in cellular and infection microbiology · 2021Article
- Ammonia inhibits energy metabolism in astrocytes in a rapid and glutamate dehydrogenase 2-dependent manner.Disease models & mechanisms · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hyperammonemia is necessary for development of the cerebral complications to liver disease including hepatic encephalopathy and cerebral edema but the mechanisms are unclear. Ammonia is taken up by the brain in proportion to its arterial concentration. The flux into the brain is most likely by both diffusion of NH3 and mediated transport of NH4 (+) . Astrocytic detoxification of ammonia involves formation of glutamine at concentrations high enough to produce cellular edema, but compensatory mechanisms reduce this effect. Glutamine can be taken up by astrocytic mitochondria and initiate the mitochondrial permeability transition but the clinical relevance is uncertain. Elevated astrocytic glutamine interferes with neurotransmission. Thus, animal studies show enhanced glutamatergic neurotransmission via the NMDA receptor which may be related to the acute cerebral complications to liver failure, while impairment of the NMDA activated glutamate-NO-cGMP pathway could relate to the behavioural changes seen in hepatic encephalopathy. Elevated glutamine also increases GABA-ergic tone, an effect which is aggravated by mitochondrial production of neurosteroids; this may relate to decreased neurotransmission and precipitation of encephalopathy by GABA targeting drugs. Hyperammonemia may compromise cerebral energy metabolism as elevated cerebral lactate is generally reported. Hypoxia is unlikely since cerebral oxygen:glucose utilisation and lactate:pyruvate ratio are both normal in clinical studies. Ammonia inhibits α-ketoglutaratedehydrogenase in isolated mitochondria, but the clinical relevance is dubious due to the observed normal cerebral oxygen:glucose utilization. Recent studies suggest that ammonia stimulates glycolysis in excess of TCA cycle activity, a hypothesis that may warrant further testing, in being in accordance with the limited clinical observations.
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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.