Regional cerebral edema and chloride space in galactosamine-induced liver failure in rats

Abstract

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...

Tumour necrosis factor-α affects blood-brain barrier permeability and tight junction-associated occludin in acute liver failure

“…We also found that ECs shrank and the number of vesicles changed, consistent with previous studies (16, 17). An increased number of vesicles could enhance communication with the environment, which could cause fluid and other toxic substances to be transported into the brain through dysfunctional ECs, which could, in turn, lead to brain oedema.…”

“…Disruption of BBB structures is the basis of vasogenic oedema. To date, few studies have observed TJ ultramicrostructures in the brain tissue from ALF animal models or patients (15, 16). We found TJ disruption or distortion in both ALF animal models and patients, which could be another important determinant of increased BBB permeability in ALF.…”

“…It is believed to be directly involved in barrier and fence functions (11–14), and although previous studies have offered insight into the molecular structure of TJs, little is known about their regulation under physiological and pathophysiological conditions. Few studies are available on the BBB ultrastructure or TJ changes during liver failure (4, 15, 16).…”

Subtle BBB alterations in brain edema associated with acute liver failure

“…The tight junction was intact. The results from our lab are consistent with the previous reports on the brains from humans and animals with ALF (Potvin et al, 1984; Traber et al, 1987; Kato et al, 1992; Gove et al, 1997). These findings collectively corroborate that BBB dysfunction is associated with increased permeability only to small molecules like water and ammonia but is not necessarily associated with a structural breakdown.…”

Magnetic resonance analysis of the effects of acute ammonia intoxication on rat brain. Role of NMDA receptors

“…However, in hypothalamus ammonia would induce mainly astrocytes swelling and cytotoxic edema, as reflected by decreased ADC. A differential induction of vasogenic and cytotoxic edema in some brain areas in acute liver failure in rats injected with galactosamine has been reported by Gove et al. (1997).…”