The brain in experimental portal‐systemic encephalopathy. II. Water and electrolyte changes

Pilbeam, C. M.; Anderson, R. McD.; Bhathal, P. S.

doi:10.1002/path.1711400404

Cited by 19 publications

(8 citation statements)

References 26 publications

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“…Moreover, neither has shown the presence of low-grade brain edema. 40,41 The model proposed here has several interesting features: First, it is a reproducible model. Most of the animals reach the desired state of liver impairment and hyperammonemia; 90% develop cirrhosis or advanced liver fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Brain edema and inflammatory activation in bile duct ligated rats with diet-induced hyperammonemia: A model of hepatic encephalopathy in cirrhosis

et al. 2006

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Studies of the pathogenesis of hepatic encephalopathy are hampered by the lack of a satisfactory animal model. We examined the neurological features of rats after bile duct ligation fed a hyperammonemic diet (BDL؉HD). Six groups were studied: sham, sham pair-fed, hyperammonemic, bile duct ligation (BDL), BDL pair fed, and BDL؉HD. The BDL؉HD rats were made hyperammonemic via an ammonia-containing diet that began 2 weeks after operation. One week later, the animals were sacrificed. BDL؉HD rats displayed an increased level of cerebral ammonia and neuroanatomical characteristics of hepatic encephalopathy (HE), including the presence of type II Alzheimer astrocytes. Both BDL and BDL؉HD rats showed activation of the inflammatory system. BDL؉HD rats showed an increased amount of brain glutamine, a decreased amount of brain myo-inositol, and a significant increase in the level of brain water. In coordination tests, BDL؉HD rats showed severe impairment of motor activity and performance as opposed to BDL rats, whose results seemed only mildly affected. In conclusion, the BDL؉HD rats displayed similar neuroanatomical and neurochemical characteristics to human HE in liver cirrhosis. Brain edema and inflammatory activation can be detected under these circumstances. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html). H epatic encephalopathy (HE) is a severe neuropsychiatric complication in both acute and chronic liver failure. Although the pathophysiology of this disorder is incompletely understood, there is agreement on the important role of neurotoxins in its development, especially ammonia. 1 Neuropathologically, HE in chronic liver disease is characterized by astrocytic rather than neuronal changes. 2 Histopathology studies of brain sections from patients with cirrhosis who died in hepatic coma show the presence of changes known as Alzheimer type II astrocytosis. These astrocytes display a specific characteristic of swollen cytoplasm containing a large pale nucleus, with prominent nucleolus and patches of heterochromatin associated with the nuclear envelope. 2 Recently, a new pathophysiological hypothesis has been developed, emphasizing the role of low-grade brain edema in the pathogenesis of HE in chronic liver disease. 3 Following this theoretical model, the presence of a lowgrade astrocyte swelling could have important functional consequences despite the absence of clinically overt increases of intracranial pressure. 3

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Section: Discussionmentioning

confidence: 99%

Brain edema and inflammatory activation in bile duct ligated rats with diet-induced hyperammonemia: A model of hepatic encephalopathy in cirrhosis

et al. 2006

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“…However, no inwith encephalopathy caused by fulminant hepatic failure. 17 Chloride space as determined in the present study 21 has crease in the chloride space was found in the forebrain region, where a significant increase in water content was been used to assess extracellular space in the brain 37,38 and other fluid compartments. 39 The increased hindbrain shown, which would suggest a cytotoxic mechanism.…”

Section: Acute Liver Failure Caused By Galactosamine At a Latermentioning

confidence: 99%

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

et al. 1997

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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.

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“…In other studies of various models of AHF, edema became measurable only at the later stages of encephalopathy (Traber et al, 1986;Dejong et al, 1992;Swain et al, 1992) . Because glutamine synthesis occurs predominantly in astrocytes, these cells may suffer disproportionately from edema, and this may account for the astrocyte swelling reported in hyperammonemic states (Pillbeam et al ., 1983), as well as secondary metabolic abnormalities leading to astrocyte dysfunction .…”

Section: Osmotic Effects Of Increased Levels Of Metabolitesmentioning

confidence: 99%

Metabolic Abnormalities and Grade of Encephalopathy in Acute Hepatic Failure

Hawkins

1994

Journal of Neurochemistry

111

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Acute hepatic failure is associated with many biochemical abnormalities in plasma and brain . Changes that correlate well with the degree of behavioral impairment may be important factors in the development of encephalopathy . We measured the concentrations of intermediary metabolites, ammonia, and amino acids in brain and plasma and the rate of whole-brain glucose utilization in rats with an acutely devascularized liver . In all rats an estimate of the grade of encephalopathy (reflected by behavioral impairment) was made . Rats underwent portacaval shunting and hepatic artery ligation (or sham operation) and were kept normoglycemic and normothermic thereafter . We sampled blood and whole brain (by near-instantaneous freeze-blowing) 2, 4, or 6 h later. There were no alterations in levels of high-energy phosphate metabolites in the brain or in metabolites associated with the glycolytic pathway and Krebs cycle, except lactate and pyruvate . Brain glucose use was decreased similarly at all times after surgery. Levels of ammonia and many amino acids were increased in brain and plasma ; brain aspartate, glutamate, and arginine levels were decreased . The increases in content of plasma ammonia and brain glutamine, proline, alanine, and aromatic amino acids and the decreases in brain aspartate and glutamate were most strongly correlated with behavioral impairment .

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The brain in experimental portal‐systemic encephalopathy. II. Water and electrolyte changes

Cited by 19 publications

References 26 publications

Brain edema and inflammatory activation in bile duct ligated rats with diet-induced hyperammonemia: A model of hepatic encephalopathy in cirrhosis

Brain edema and inflammatory activation in bile duct ligated rats with diet-induced hyperammonemia: A model of hepatic encephalopathy in cirrhosis

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

Metabolic Abnormalities and Grade of Encephalopathy in Acute Hepatic Failure

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