ArticleNeurological research2011
Ammonia-induced brain swelling and neurotoxicity in an organotypic slice model.
Article in Neurological research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 39 citations in OpenAlex.
- Exendin-4 protects brain endothelial cell damage against hyperammonemic condition.Biochemistry and biophysics reports · 2026Article
- Bioactive Phenolics ofInternational journal of molecular sciences · 2025Article
- Risk of Cerebral Aneurysm Rupture After Liver Transplantation: Development and Validation of a Hemorrhagic Stroke Scoring Model.Journal of Korean medical science · 2024Article
- Lessons on brain edema in HE: from cellular to animal models and clinical studies.Metabolic brain disease · 2024Review
- Review
- Three-dimensional human neural culture on a chip recapitulating neuroinflammation and neurodegeneration.Nature protocols · 2023Review
- New Insight Into Mechanisms of Hepatic Encephalopathy: An Integrative Analysis Approach to Identify Molecular Markers and Therapeutic Targets.Bioinformatics and biology insights · 2023Article
- Recommendations for the Diagnosis and Therapeutic Management of Hyperammonaemia in Paediatric and Adult Patients.Nutrients · 2022Review
- Protective Effect of Low Dose of Methamphetamine on The Amount of Extracellular Glutamine in Primary Fetal Human Astrocytes Induced by Amyloid Beta.Cell journal · 2022Article
- Enhanced recruitment of glutamate receptors underlies excitotoxicity of mitral cells in acute hyperammonemia.Frontiers in cellular neuroscience · 2022Article
- Long Noncoding RNAs Regulate Hyperammonemia-Induced Neuronal Damage in Hepatic Encephalopathy.Oxidative medicine and cellular longevity · 2022Article
- The neurogliovascular unit in hepatic encephalopathy.JHEP reports : innovation in hepatology · 2021Review
- Persistent hyperammonia and altered concentrations of urea cycle metabolites in a 5-day swine experiment of sepsis.Scientific reports · 2021Article
- Lycopene suppresses palmitic acid-induced brain oxidative stress, hyperactivity of some neuro-signalling enzymes, and inflammation in female Wistar rat.Scientific reports · 2021Article
- The Cerebral Effect of Ammonia in Brain Aging: Blood-Brain Barrier Breakdown, Mitochondrial Dysfunction, and Neuroinflammation.Journal of clinical medicine · 2021Review
- Increasing cellular lifespan with a flow system in organotypic culture of the Laterodorsal Tegmentum (LDT).Scientific reports · 2019Article
- Hyperammonemia in Hepatic Encephalopathy.Journal of clinical and experimental hepatology · 2018Review
- Review
- Neurotoxicity of Ammonia.Neurochemical research · 2017Review
- Acute Hyperammonemia Induces NMDA-Mediated Hypophosphorylation of Intermediate Filaments Through PP1 and PP2B in Cerebral Cortex of Young Rats.Neurotoxicity research · 2016Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
objectivesAcute liver failure (ALF) produces cerebral dysfunction and edema, mediated in part by elevated ammonia concentrations, often leading to coma and death. The pathophysiology of cerebral edema in ALF is incompletely understood. In vitro models of the cerebral effects of ALF have predominately consisted of dissociated astrocyte cultures or acute brain slices. We describe a stable long-term culture model incorporating both neural and glial elements in a three-dimensional tissue structure offering significant advantages to the study of astrocytic-neuronal interactions in the pathophysiology of cerebral edema and dysfunction in ALF.
methodsWe utilized chronic organotypic slice cultures from mouse forebrain, applying ammonium acetate in iso-osmolar fashion for 72 hours. Imaging of slice thickness to assess for tissue swelling was accomplished in living slices with optical coherence tomography, and confocal microscopy of fluorescence immunochemical and histochemical staining served to assess astrocyte and neuronal numbers, morphology, and volume in the fixed brain slices.
resultsAmmonia exposure at 1-10 mM produced swelling of immunochemically identified astrocytes, and at 10 mM resulted in macroscopic tissue swelling, with slice thickness increasing by about 30%. Astrocytes were unchanged in number. In contrast, 10 mM ammonia treatment severely disrupted neuronal morphology and reduced neuronal survival at 72 hours by one-half. DISCUSSION: Elevated ammonia produces astrocytic swelling, tissue swelling, and neuronal toxicity in cerebral tissues. Ammonia-treated organotypic brain slice cultures provide an In vitro model of cerebral effects of conditions relevant to ALF, applicable to pathophysiological investigations.
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