toxic edema, in which inhibition of ouabain-sensitive sodium The pathogenesis of cerebral edema, which is a major transport is characteristic, a net increase in intracellular wacomplication of fulminant hepatic failure, is poorly unter occurs, reflecting impaired cellular osmo-regulation. 5 Cerderstood. In previous studies, increased regional brain tain common mechanisms appear to be involved in both these water content was observed in rats at an early stage of forms of edema, making distinction between them less clear. 6 acute liver failure caused by galactosamine. At a laterIn a postmortem study of the ultrastructure of brain capillarstage when the animals had developed deep coma, brain ies of patients dying from fulminant hepatic failure, marked water content was reduced, possibly as a result of generintracellular swelling of perivascular astrocytes was observed alized dehydration. In the present investigation, we consistent with a mainly cytotoxic mechanism, but increases have determined brain water content at a late stage of in the number of vesicles and vacuoles in endothelial cells liver failure, 48 hours after galactosamine, in animals were also seen, suggesting a vasogenic component. 7 Conflictthat had been maintained in fluid balance by continuous ing results on this were obtained in earlier animal studies, 6 intraperitoneal infusion of glucose solution. In these aniand it has been suggested that an initial cytotoxic injury mals, brain water content, determined from the ratio of evolves into vasogenic edema. 8,9 Some of these studies have wet to dry weight, showed a greater increase than that been criticized as describing a phenomenon that occurs in observed previously at the early stage (hindbrain region essentially moribund animals. 10,11 [cerebellum, pons, and brain stem] increased by 4.2%;In previous studies using rats with galactosamine-induced forebrain region increased by 1.4% compared with conliver failure, we found a small increase (0.5%) in hindbrain trols). Regional analysis of brain water, using a tissue-(cerebellum, pons, and brain stem) water content at an early specific gravity method, showed a significant increase stage of liver failure, 43 hours after galactosamine. 12 This was in cerebellar gray matter water content. Analysis of chloin agreement with the observations of Groflin and Tholen, 13 ride space showed the extra fluid to be mainly extracelusing the same model, in which the water contents of cerebellular in the hindbrain region, but not in the forebrain lum and brain stem were increased when the rats were mildly region. Ultrastructural examination of capillaries in encephalopathic. However, in both these studies at later gray matter from cerebellum and cerebrum showed no stages of acute liver failure when the rats progressed to deep evidence of gross disruption of the tight junctions. Swellcoma (immobility and/or gross ataxia), fore-and hindbrain ing of the astroglial foot processes was observed in the water contents were reduced in comparison with animals studcerebellar gray m...