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.

Brain lactate by magnetic resonance spectroscopy during fulminant hepatic failure in the dog

“…supported by past reports using rats 36,45,46 and rabbits. 47,48 Although the current study was conducted in an experimental facility at 9.4 T, observations made in this study regarding brain lactate are transferable to the clinical setting.…”

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.…”

The effect of hypertonic sodium chloride on intracranial pressure in patients with acute liver failure

“…19 Endothelial swelling has been shown to occur in cerebral blood vessels in patients with ALF, as well as in animal models of this disease. 20,21 Generally, a reduction in cerebral blood flow coupled with a reduction in cerebral metabolic rate early in the course of high-grade hepatic encephalopathy in ALF is followed by gradual cerebral vasodilation and an increase in cerebral blood volume in severe cases. 4,22 Variation in regional cerebral blood flow, however, has been reported in patients with ALF; this finding suggests that some areas of the brain may be more prone to ischemia.…”