ArticleHepatology (Baltimore, Md.)2017
Ammonia mediates cortical hemichannel dysfunction in rodent models of chronic liver disease.
Article in Hepatology (Baltimore, Md.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- The evidence for the physiological effects of lactate on the cerebral microcirculation: a systematic review.Journal of neurochemistry · 2019Pooled it
- Differential metabolic and cellular brain regional susceptibility in adult rats with chronic liver disease.Metabolic brain disease · 2026Article
- Encephalopathy: Cause, Pathogenesis, and Treatment.MedComm · 2026Review
- Mechanistic insights into the liver-brain axis during chronic liver disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Cerebral oxygen saturation in cirrhotic patients with gastro-intestinal bleeding, a near infrared spectroscopy study.Metabolic brain disease · 2025Article
- Research progress on the interaction between multiple organ-brain axes and perioperative neurocognitive disorders: a narrative review.Frontiers in aging neuroscience · 2025Review
- Ammonia-induced stress response in liver disease progression and hepatic encephalopathy.Nature reviews. Gastroenterology & hepatology · 2024Review
- Effects of oxidative stress on hepatic encephalopathy pathogenesis in mice.Nature communications · 2023Article
- The role of brain inflammation and abnormal brain oxygen homeostasis in the development of hepatic encephalopathy.Metabolic brain disease · 2023Review
- Regulation of mild cognitive impairment associated with liver disease by humoral factors derived from the gastrointestinal tract and MRI research progress: a literature review.Frontiers in neuroscience · 2023Review
- Abnormal brain oxygen homeostasis in an animal model of liver disease.JHEP reports : innovation in hepatology · 2022Article
- Hyperammonaemia induces mitochondrial dysfunction and neuronal cell death.JHEP reports : innovation in hepatology · 2022Article
- Genome-Wide Knockout Screen Identifies EGLN3 Involving in Ammonia Neurotoxicity.Frontiers in cell and developmental biology · 2022Article
- The Synergy between Organ-on-a-Chip and Artificial Intelligence for the Study of NAFLD: From Basic Science to Clinical Research.Biomedicines · 2021Review
- Possible Association Between DHEA and PKCε in Hepatic Encephalopathy Amelioration: A Pilot Study.Frontiers in veterinary science · 2021Article
- Mechanosensory Signaling in Astrocytes.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- The effect of general anaesthetics on brain lactate release.European journal of pharmacology · 2020Article
- The Role of Intestinal Bacteria and Gut-Brain Axis in Hepatic Encephalopathy.Frontiers in cellular and infection microbiology · 2020Review
- Resveratrol Restores Neuronal Tight Junction Proteins Through Correction of Ammonia and Inflammation in CClMolecular neurobiology · 2019Article
- Impaired brain glymphatic flow in experimental hepatic encephalopathy.Journal of hepatology · 2019Article
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
The pathogenesis of hepatic encephalopathy (HE) in cirrhosis is multifactorial and ammonia is thought to play a key role. Astroglial dysfunction is known to be present in HE. Astrocytes are extensively connected by gap junctions formed of connexins, which also exist as functional hemichannels allowing exchange of molecules between the cytoplasm and the extracellular milieu. The astrocyte-neuron lactate shuttle hypothesis suggests that neuronal activity is fueled (at least in part) by lactate provided by neighboring astrocytes. We hypothesized that in HE, astroglial dysfunction could impair metabolic communication between astrocytes and neurons. In this study, we determined whether hyperammonemia leads to hemichannel dysfunction and impairs lactate transport in the cerebral cortex using rat models of HE (bile duct ligation [BDL] and induced hyperammonemia) and also evaluated the effect of ammonia-lowering treatment (ornithine phenylacetate [OP]). Plasma ammonia concentration in BDL rats was significantly reduced by OP treatment. Biosensor recordings demonstrated that HE is associated with a significant reduction in both tonic and hypoxia-induced lactate release in the cerebral cortex, which was normalized by OP treatment. Cortical dye loading experiments revealed hemichannel dysfunction in HE with improvement following OP treatment, while the expression of key connexins was unaffected.
conclusionThe results of the present study demonstrate that HE is associated with central nervous system hemichannel dysfunction, with ammonia playing a key role. The data provide evidence of a potential neuronal energy deficit due to impaired hemichannel-mediated lactate transport between astrocytes and neurons as a possible mechanism underlying pathogenesis of HE. (Hepatology 2017;65:1306-1318).
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