Brain edema and
intracranial hypertension are major complications of
fulminant hepatic failure. We investigated the development of
brain edema and monitored intracranial pressure in rabbits with
toxic hepatitis induced by
galactosamine. Using a gravimetric technique to assay small tissue samples, we found that brain water was increased in cortical grey matter, but not in subcortical, mesencephalic, and pontine white matter, or in the cerebellum. The proportion of water in cerebral grey matter in control animals was 80.96% +/- 0.49% with significant elevations to 81.96% +/- 0.47% and 82.95% +/- 1.49% in mild and severe
encephalopathy, respectively. This corresponds to mean increases in tissue volume of 5.5% and 11.7%. The hippocampal grey matter also accumulated water in severe
encephalopathy with a 30% increase in mean tissue volume. The regional increase in brain water was confirmed by the wet-dry weight method. Neither
hypotension,
hypoxia, nor severe
hypoglycemia were present to account for the
edema. Intracranial pressure was monitored continuously in unanesthetized rabbits via an intraventricular
cannula as
encephalopathy developed. The pressure was normal in the mild stage, but was intermittently elevated in animals with severe
encephalopathy. The normal range of intracranial pressure was 2-9 mmHg and the range of peak values in
galactosamine-treated rabbits was 18-55 mmHg. The regional differences in brain water accumulation suggest that cellular swelling and abnormalities in the movement of water across the blood-brain barrier may account for the
brain edema in this model.