Brain edema and the blood brain barrier in galactosamine-induced fulminant hepatic failure rats. An animal model for evaluation of liver support systems.
Rats with galactosamine-induced fulminant hepatic failure (FHF) have been a popular animal model for the evaluation of liver support systems. Because development of brain edema is a major and frequent complication during FHF, it was studied for this report. The degree of hepatocyte necrosis closely paralleled the severity of coma. Abnormalities in the orientation of hepatocellular organelles were evident as early as grade I hepatic coma, 24 hr after galactosamine-induced liver damage. Galactosamine caused a characteristic pattern of hepatocyte necrosis such that the endoplasmic reticulum completely surrounded the nucleus to cause karyolysis and subsequent cell death. Quantitative measurements of brain water content revealed evidence of brain edema with increasing severity of coma. Brain edema resulted in a greater than 4% swelling of the brain during this period. Light microscopy showed increasing cerebral and cerebellar edema during progressive stages of FHF. Electron microscopy studies revealed evidence of progressive cerebral edema, particularly in the perivascular region of cerebral capillaries. Marked swelling of perivascular astrocytes was evident as early as 24 hr after galactosamine-induced FHF when the animals were in Grade I hepatic coma. Abnormal swelling and distortion of astroglia, including its subcellular organelles, and the presence of cytoplasmic vacuoles, was clearly evident during the deeper stages of hepatic coma (Grades II-IV). Trypan blue dye infusion studies revealed evidence of extensive blood-brain barrier (BBB) breakdown beginning in Grade III coma.
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Artificial Cells and Organs Research Centre, Faculty of Medicine, McGill University, Montreal, Canada.
Chang
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TM
D000818:Animals; D001253:Astrocytes / Q000648:ultrastructure; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000473:pathology; D001929:Brain Edema / Q000473:pathology*; D003593:Cytoplasm / Q000648:ultrastructure; D004195:Disease Models, Animal; D005688:Galactosamine; D006501:Hepatic Encephalopathy / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology*; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008297:Male; D009336:Necrosis; D015388:Organelles / Q000648:ultrastructure; D051381:Rats; D011919:Rats, Inbred Strains
D005688:Galactosamine