1581 Blood-brain barrier changes in acute hepatic encepha-lopathy

Abstract

Blood-to-brain transport constants (k) for ¹⁴C-α-aminoisobutyric acid (AIB), a marker of brain capillary permeability, were measured in rabbits with acute hepatic encephalopathy induced by the hepatotoxin, galactosamine (GAL). Tissue ¹⁴C-activity was assayed on 20 micron thick coronal sections of frozen rabbit brains by quantitative autoradiography; adjacent sections were prepared for histological examination. Experiments which were performed 2 and 10 hours after the administration of GLA (times when the rabbits were neurologically normal) showed no changes in the k values of AIB from the untreated controls. Eighteen hours after GAL administration, the rabbits were comatose and their brains were edematous; in addition, five-to tenfold increases in blood-brain barrier (BBB) permeability to AIB were found in gray matter (no permeability changes were detected in white matter). These observations suggest that the permeability of the BBB not only to AIB but also to other solutes (notably, Na and Cl) and to water has increased in gray matter and that the role of the BBB as a regulatory of brain volume has been compromised by these changes, thereby leading to cerebral edema. A similar pathogenesis may be involved in other diseases in which hepatic dysfunction frequently leads to acute cerebral edema, elevated intracranial pressure, and death (for example, Reye's syndrome).

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