ArticleJournal of neurochemistry2012
Ammonia increases paracellular permeability of rat brain endothelial cells by a mechanism encompassing oxidative/nitrosative stress and activation of matrix metalloproteinases.
Article in Journal of neurochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
32 citing papers in PubMed, 66 citations in OpenAlex.
- Adiponectin Inhibits Oxidative Stress and Tight Junction Protein Loss: Evidence from a Hepatic Encephalopathy Mouse Model and Brain Endothelial Cells.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Uric acid and ammonia play synergistic roles in the loss of blood-brain barrier integrity in the context of hepatic encephalopathy.Fluids and barriers of the CNS · 2025Article
- Diacerein ameliorates thioacetamide-induced hepatic encephalopathy in rats via modulation of TLR4/AQP4/MMP-9 axis.Metabolic brain disease · 2024Article
- Mitochondrial Changes in Rat Brain Endothelial Cells Associated with Hepatic Encephalopathy: Relation to the Blood-Brain Barrier Dysfunction.Neurochemical research · 2024Review
- Serum from patients with cirrhosis undergoing liver transplantation induces permeability in human pulmonary microvascular endothelial cellsFrontiers in medicine · 2024Article
- Could the Urease of the Gut BacteriumMicroorganisms · 2023Article
- Article
- Secondary Dysfunction of the Intestinal Barrier in the Pathogenesis of Complications of Acute Poisoning.Journal of evolutionary biochemistry and physiology · 2022Article
- Endogenous zinc protoporphyrin formation critically contributes to hemorrhagic stroke-induced brain damage.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- Transport of Amino Acids Across the Blood-Brain Barrier.Frontiers in physiology · 2020Review
- Hyperammonemia in Hepatic Encephalopathy.Journal of clinical and experimental hepatology · 2018Review
- Alterations in Expression and Function of ABC Family Transporters at Blood-Brain Barrier under Liver Failure and Their Clinical Significances.Pharmaceutics · 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
- Research Progress in Understanding the Relationship Between Heme Oxygenase-1 and Intracerebral Hemorrhage.Frontiers in neurology · 2018Review
- Ammonia Reduces Intracellular Asymmetric Dimethylarginine in Cultured Astrocytes Stimulating Its y⁺LAT2 Carrier-Mediated Loss.International journal of molecular sciences · 2017Article
- Multifactorial Effects on Different Types of Brain Cells Contribute to Ammonia Toxicity.Neurochemical research · 2017Review
- Solute Carriers in the Blood-Brain Barier: Safety in Abundance.Neurochemical research · 2017Review
- Ammonia promotes endothelial cell survival via the heme oxygenase-1-mediated release of carbon monoxide.Free radical biology & medicine · 2017Article
- Effects of NHCellular & molecular biology letters · 2016Article
- TGFβ1 exacerbates blood-brain barrier permeability in a mouse model of hepatic encephalopathy via upregulation of MMP9 and downregulation of claudin-5.Laboratory investigation; a journal of technical methods and pathology · 2015Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Ammonia is responsible for cerebral edema associated with acute liver failure, but the role of the vasogenic mechanism has been a matter of dispute. Here, we tested the hypothesis that ammonia induces changes in blood-brain barrier (BBB) permeability by a mechanism coupled to oxidative/nitrosative stress (ONS) evoked in the BBB-forming cerebral capillary endothelial cells. Treatment of a rat brain endothelial cell line with ammonia (5 mmol/L, 24 h) caused accumulation of ONS markers: reactive oxygen species, nitric oxide and peroxidation products of phospholipid-bound arachidonic acid, F2-isoprostanes. Concurrently, ammonia increased the activity of extracellular matrix metalloproteinases (MMP-2/MMP-9), increased cell permeability to fluorescein isothiocyanate-dextran (40 kDa), and increased the expression of y+LAT2, a transporter that mediates the uptake to the cells of the nitric oxide precursor, arginine. The increase of cell permeability was ameliorated upon co-treatment with a MMP inhibitor, SB-3CT and with an antioxidant, glutathione diethyl ester, which also reduced F2-isoprostanes. Ammonia-induced ONS was attenuated by cytoprotective agents l-ornithine, phenylbutyrate, and their conjugate l-ornithine phenylbutyrate, an ammonia-trapping drug used to treat hyperammonemia. The results support the concept that ONS and ONS-related activation of MMPs in cerebral capillary endothelial cells contribute to the alterations in BBB permeability and to the vasogenic component of cerebral edema associated with acute liver failure.
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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.