ArticleNeuromolecular medicine2014
Blocking NMDA receptors delays death in rats with acute liver failure by dual protective mechanisms in kidney and brain.
Article in Neuromolecular medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- Guanosine Attenuates Astrocyte-Associated Glutamatergic Dysregulation and Improves Survival in Acute Liver Failure-Induced Hepatic Encephalopathy.Metabolites · 2026Article
- [Clinical analysis of blood ammonia levels for predicting survival following transjugular intrahepatic portosystemic shunt in patients with cirrhosis].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Article
- Glutamine and Albumin Levels in Cerebrospinal Fluid Are Correlated with Neurological Severity in an Experimental Model of Acute Hepatic Encephalopathy.Metabolites · 2025Article
- Preface for the Vicente Felipo Honorary Issue of Neurochemical Research.Neurochemical research · 2024Article
- Narrative Review: Low-Dose Ketamine for Pain Management.Journal of clinical medicine · 2023Review
- 2021 ISHEN guidelines on animal models of hepatic encephalopathy.Liver international : official journal of the International Association for the Study of the Liver · 2021Review
- Glutamate-Gated NMDA Receptors: Insights into the Function and Signaling in the Kidney.Biomolecules · 2020Review
- The Role of Intestinal Bacteria and Gut-Brain Axis in Hepatic Encephalopathy.Frontiers in cellular and infection microbiology · 2020Review
- Acute Liver Failure Induces Glial Reactivity, Oxidative Stress and Impairs Brain Energy Metabolism in Rats.Frontiers in molecular neuroscience · 2019Article
- Concurrent assessment of calpain and caspase3 activities in brains of mice with acetaminophen-induced acute hepatic encephalopathy.Metabolic brain disease · 2017Article
- Guanosine Exerts Neuroprotective Effect in an Experimental Model of Acute Ammonia Intoxication.Molecular neurobiology · 2017Article
- Recent advances in hepatic encephalopathy.F1000Research · 2017Review
- Acute Hyperammonemia Induces NMDA-Mediated Hypophosphorylation of Intermediate Filaments Through PP1 and PP2B in Cerebral Cortex of Young Rats.Neurotoxicity research · 2016Article
- Hepatic encephalopathy induces site-specific changes in gene expression of GluN1 subunit of NMDA receptor in rat brain.Metabolic brain disease · 2015Article
- Article
- Potential role of Plasmodium falciparum-derived ammonia in the pathogenesis of cerebral malaria.Frontiers in neuroscience · 2015Article
- Brain edema in acute liver failure: mechanisms and concepts.Metabolic brain disease · 2014Review
Corrections and comments
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Authors and funding
17 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Treatment of patients with acute liver failure (ALF) is unsatisfactory and mortality remains unacceptably high. Blocking NMDA receptors delays or prevents death of rats with ALF. The underlying mechanisms remain unclear. Clarifying these mechanisms will help to design more efficient treatments to increase patient's survival. The aim of this work was to shed light on the mechanisms by which blocking NMDA receptors delays rat's death in ALF. ALF was induced by galactosamine injection. NMDA receptors were blocked by continuous MK-801 administration. Edema and cerebral blood flow were assessed by magnetic resonance. The time course of ammonia levels in brain, muscle, blood, and urine; of glutamine, lactate, and water content in brain; of glomerular filtration rate and kidney damage; and of hepatic encephalopathy (HE) and intracranial pressure was assessed. ALF reduces kidney glomerular filtration rate (GFR) as reflected by reduced inulin clearance. GFR reduction is due to both reduced renal perfusion and kidney tubular damage as reflected by increased Kim-1 in urine and histological analysis. Blocking NMDA receptors delays kidney damage, allowing transient increased GFR and ammonia elimination which delays hyperammonemia and associated changes in brain. Blocking NMDA receptors does not prevent cerebral edema or blood-brain barrier permeability but reduces or prevents changes in cerebral blood flow and brain lactate. The data show that dual protective effects of MK-801 in kidney and brain delay cerebral alterations, HE, intracranial pressure increase and death. NMDA receptors antagonists may increase survival of patients with ALF by providing additional time for liver transplantation or regeneration.
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