Cerebral abnormalities in hepatectomized rats with acute hepatic coma.

When hepatectomized rats develop hepatic coma, they are found to have cerebral edema, together with a failure of the blood-brain barrier to contain materials usually limited to the circulation. The present studies were carried out to characterize the associated ultrastructural changes in the barrier. Rats were allowed to develop hepatic coma after a two-stage hepatectomy. Electrocortical and behavior monitoring during this period indicated deterioration similar to that seen in man with acute liver injury; the water contents of the brains of the animals in hepatic coma were increased. Electron microscopic examination of the brains from control rats and animals with hepatic coma were carried out after perfusion fixation. The examination of the brains from the comatose animals showed the appearance of greatly increased numbers of vesicles in the capillary endothelium and a marked watery swelling of adjacent astrocytes, which seemed to begin in foot processes and then to spread through the cell. Intravenous peroxidase was given to most rats in the late stages of coma, and the tracer was found to be included within the capillary endothelial vesicles. Occasional accumulations of peroxidase in the underlying capillary basement membrane were found. No interendothelial cell distruption was found. Low molecular weight microperoxidase was used as well as horseradish peroxidase; the results were the same with both compounds. The findings indicate as association between capillary endothelial vesicle formation and the cerebral edema found in animals with hepatic coma following hepatectomy.