ReviewNeurochemical research2015
Ammonia, like K(+), stimulates the Na(+), K(+), 2 Cl(-) cotransporter NKCC1 and the Na(+),K(+)-ATPase and interacts with endogenous ouabain in astrocytes.
Review in Neurochemical research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Soil to Synapse: Molecular Insights into the Neurotoxicity of Common Gardening Chemicals in Alzheimer's and Parkinson's Disease.International journal of molecular sciences · 2025Review
- [Effects of Inhibiting the NKCC1/AQP4 Pathway on Neurological Injury Improvement in a Rat Model of High-Altitude Cerebral Edema].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025Article
- Sex-Dependent Signaling Pathways Underlying Seizure Susceptibility and the Role of Chloride Cotransporters.Cells · 2019Review
- Cryo-EM structures of KdpFABC suggest a KNature communications · 2018Article
- Hyperammonemia in Hepatic Encephalopathy.Journal of clinical and experimental hepatology · 2018Review
- Blood-Brain Barrier Permeability Is Exacerbated in Experimental Model of Hepatic Encephalopathy via MMP-9 Activation and Downregulation of Tight Junction Proteins.Molecular neurobiology · 2018Article
- Severe Convulsions and Dysmyelination in Both Jimpy and Cx32/47Neurochemical research · 2017Review
- Multifactorial Effects on Different Types of Brain Cells Contribute to Ammonia Toxicity.Neurochemical research · 2017Review
- Astrocyte Cultures Mimicking Brain Astrocytes in Gene Expression, Signaling, Metabolism and KNeurochemical research · 2017Article
- Ammonia as a Potential Neurotoxic Factor in Alzheimer's Disease.Frontiers in molecular neuroscience · 2016Review
- Role of the Astrocytic Na(+), K(+)-ATPase in K(+) Homeostasis in Brain: K(+) Uptake, Signaling Pathways and Substrate Utilization.Neurochemical research · 2015Review
- Why are astrocytes important?Neurochemical research · 2015Review
- Article
- Ammonium activates ouabain-activated signalling pathway in astrocytes: therapeutic potential of ouabain antagonist.Current neuropharmacology · 2014Article
- Antagonists of the Vasopressin V1 Receptor and of the β(1)-Adrenoceptor Inhibit Cytotoxic Brain Edema in Stroke by Effects on Astrocytes - but the Mechanisms Differ.Current neuropharmacology · 2014Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Brain edema during hepatic encephalopathy or acute liver failure as well as following brain ischemia has a multifactorial etiology, but it is a dangerous and occasionally life-threatening complication because the brain is enclosed in the rigid skull. During ischemia the extracellular K(+) concentration increases to very high levels, which when energy becomes available during reperfusion stimulate NKCC1, a cotransporter driven by the transmembrane ion gradients established by the Na(+),K(+)-ATPase and accumulating Na(+), K(+) and 2 Cl(-) together with water. This induces pronounced astrocytic swelling under pathologic conditions, but NKCC1 is probably also activated, although to a lesser extent, during normal brain function. Redistribution of ions and water between extra- and intracellular phases does not create brain edema, which in addition requires uptake across the blood-brain barrier. During hepatic encephalopathy and acute liver failure a crucial factor is the close resemblance between K(+) and NH4(+) in their effects not only on NKCC1 and Na(+),K(+)-ATPase but also on Na(+),K(+)-ATPase-induced signaling by endogenous ouabains. These in turn activate production of ROS and nitrosactive agents which slowly sensitize NKCC1, explaining why cell swelling and brain edema generally are delayed under hyperammonemic conditions, although very high ammonia concentrations can cause immediate NKCC1 activation.
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