title: Mechanisms of brain edema in acute liver failure and impact of novel therapeutic interventions.
abstract: Continued elucidation of the mechanisms of brain edema in acute liver failure (ALF) has established ammonia and the astrocyte as major players in its pathogenesis. The metabolism of ammonia to glutamine appears to be a requisite, and is followed by an osmotic disturbance in the brain, mitochondrial dysfunction with oxidative/nitrosative stress, and alterations of brain glucose metabolism. Cerebral blood flow (CBF) is also altered in ALF and strongly influence the development of brain edema and intracranial hypertension. Additional factors such as systemic inflammation, alterations of the brain extracellular concentration of amino acids and neurotransmitters, and others have been identified and may contribute to the cerebral alterations of ALF. Such pathophysiologic insights are reflected in the various clinical trials of novel therapeutic interventions using ammonia-lowering agents, N-acetylcysteine, hypertonic saline, indomethacin, high-volume plasmapheresis, bio-artificial liver assist devices, albumin dialysis and mild hypothermia.
authors.affiliation: Neuroscience Research Unit, Hôpital Saint-Luc (CHUM), Université de Montréal, Montréal, H2X3J4, QC., Canada.
authors.forename: Javier
authors.initials: J
authors.lastname: Vaquero
authors.forename: Roger F
authors.initials: RF
authors.lastname: Butterworth
mesh_terms: D000641:Ammonia / Q000097:blood; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D001928:Brain Diseases, Metabolic / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D001929:Brain Edema / Q000209:etiology* / Q000503:physiopathology* / Q000628:therapy; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D005973:Glutamine / Q000378:metabolism; D006501:Hepatic Encephalopathy / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D006801:Humans; D022124:Hyperammonemia / Q000150:complications* / Q000628:therapy; D017114:Liver Failure, Acute / Q000150:complications*
chemical_list: D005973:Glutamine; D000641:Ammonia