The role of changes in blood-brain barrier permeability in the pathogenesis of hepatic encephalopathy remains uncertain. To test the hypothesis that brain microvessel permeability is nonselectively increased in hepatic encephalopathy we measured the blood-brain barrier permeability-surface area product in rats with acute liver failure induced by intraperitoneal injection of galactosamine. The permeability-surface area products to the diffusion-limited tracers, sucrose and methylaminoisobutyric acid, were determined as a measure of blood-brain barrier permeability. Animals were examined 24,36 and 42 hr after injection, at times when they were stuporous, but not comatose. No significant elevations of the permeability-surface area products for either compound were detected in clinically affected experimental animals when compared to con- trols. Our results indicate there is no generalized increase in brain vascular permeability during hepatic insufficiency in precomatose animals.
The mechanism by which hepatic encephalopathy is produced remains unclear. Several investigators have reported increases in blood-brain barrier (BBB) permeability following experimental liver injury (1-3), and they propose that these changes play a role in the pathogenesis of encephalopathy. Other investigators found no generalized BBB opening (4-6). This discrepancy may be explained, in part, by the low sensitivity of the method used to measure BBB permeability. Most of these studies employed the single-pass, intracarotid injection technique. However, when used to measure brain uptake of poorly diffusible compounds, this method requires large corrections for tracer retained within the intravascular compartment (7). The integrity of the BBB can be meas-