title: Regional cerebral edema and chloride space in galactosamine-induced liver failure in rats.
abstract: The pathogenesis of cerebral edema, which is a major complication of fulminant hepatic failure, is poorly understood. In previous studies, increased regional brain water content was observed in rats at an early stage of acute liver failure caused by galactosamine. At a later stage when the animals had developed deep coma, brain water content was reduced, possibly as a result of generalized dehydration. In the present investigation, we have determined brain water content at a late stage of liver failure, 48 hours after galactosamine, in animals that had been maintained in fluid balance by continuous intraperitoneal infusion of glucose solution. In these animals, brain water content, determined from the ratio of wet to dry weight, showed a greater increase than that observed previously at the early stage (hindbrain region [cerebellum, pons, and brain stem] increased by 4.2%; forebrain region increased by 1.4% compared with controls). Regional analysis of brain water, using a tissue-specific gravity method, showed a significant increase in cerebellar gray matter water content. Analysis of chloride space showed the extra fluid to be mainly extracellular in the hindbrain region, but not in the forebrain region. Ultrastructural examination of capillaries in gray matter from cerebellum and cerebrum showed no evidence of gross disruption of the tight junctions. Swelling of the astroglial foot processes was observed in the cerebellar gray matter. These results suggest that both vasogenic and cytotoxic mechanisms of edema formation occur in the brain during liver failure.
authors.affiliation: Institute of Liver Studies, King's College School of Medicine and Dentistry, London, England.
authors.forename: C D
authors.initials: CD
authors.lastname: Gove
authors.forename: R D
authors.initials: RD
authors.lastname: Hughes
authors.forename: R J
authors.initials: RJ
authors.lastname: Ede
authors.forename: R
authors.initials: R
authors.lastname: Williams
mesh_terms: D000208:Acute Disease; D000818:Animals; D001834:Body Water; D001921:Brain / Q000098:blood supply; D001923:Brain Chemistry; D001929:Brain Edema / Q000097:blood / Q000209:etiology*; D002196:Capillaries / Q000648:ultrastructure; D002712:Chlorides / Q000032:analysis*; D004730:Endothelium, Vascular / Q000648:ultrastructure; D005688:Galactosamine; D007365:Intercellular Junctions / Q000648:ultrastructure; D017093:Liver Failure / Q000097:blood / Q000139:chemically induced / Q000150:complications*; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002712:Chlorides; D005688:Galactosamine