title: Alterations of blood brain barrier function in hyperammonemia: an overview.
abstract: Ammonia is a neurotoxin involved in the pathogenesis of neurological conditions associated with hyperammonemia, including hepatic encephalopathy, a condition associated with acute--(ALF) or chronic liver failure. This article reviews evidence that apart from directly affecting the metabolism and function of the central nervous system cells, ammonia influences the passage of different molecules across the blood brain barrier (BBB). A brief description is provided of the tight junctions, which couple adjacent cerebral capillary endothelial cells to each other to form the barrier. Ammonia modulates the transcellular passage of low-to medium-size molecules, by affecting their carriers located at the BBB. Ammonia induces interrelated aberrations of the transport of the large neutral amino acids and aromatic amino acids (AAA), whose influx is augmented by exchange with glutamine produced in the course of ammonia detoxification, and maybe also modulated by the extracellularly acting gamma-glutamyl moiety transferring enzyme, gamma-glutamyl-transpeptidase. Impaired AAA transport affects neurotransmission by altering intracerebral synthesis of catecholamines (serotonin and dopamine), and producing "false neurotransmitters" (octopamine and phenylethylamine). Ammonia also modulates BBB transport of the cationic amino acids: the nitric oxide precursor, arginine, and ornithine, which is an ammonia trap, and affects the transport of energy metabolites glucose and creatine. Moreover, ammonia acting either directly or in synergy with liver injury-derived inflammatory cytokines also evokes subtle increases of the transcellular passage of molecules of different size (BBB "leakage"), which appears to be responsible for the vasogenic component of cerebral edema associated with ALF.
authors.affiliation: Departament of Neurotoxicology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 02-106 Warszawa, Pawińskiego 5, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Skowrońska
authors.forename: Jan
authors.initials: J
authors.lastname: Albrecht
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000641:Ammonia / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D001929:Brain Edema / Q000209:etiology; D006801:Humans; D022124:Hyperammonemia / Q000378:metabolism*; D051379:Mice; D051381:Rats
chemical_list: D000596:Amino Acids; D000641:Ammonia