Experimental bilirubin encephalopathy: importance of total bilirubin, protein binding, and blood-brain barrier.

Abstract

The cause of bilirubin encephalopathy has been variously ascribed to elevated total serum bilirubin concentration, high free bilirubin levels (or impaired albumin binding), and disruption of the blood-brain barrier. An experimental rat model for acute bilirubin encephalopathy was developed in which these three factors could be varied independently. Osmotic opening of the blood-brain barrier in the right hemisphere was produced by infusing a hypertonic arabinose solution into the right carotid artery. The total bilirubin level and bilirubin binding state were varied by adjusting the amount of bilirubin infused intravenously and/or by infusing human serum albumin. Brain electrical activity (EEG) served as an indicator of developing encephalopathy. Neither staining nor EEG changes occurred if the blood-brain barrier remained intact. Bilirubin staining without EEG evidence of encephalopathy sometimes occurred when the blood-brain barrier was open. Discriminant analysis showed that EEG changes were best predicted by the degree of blood-brain barrier opening (as indicated by brain bilirubin content) and by the quality of serum bilirubin binding. Serum total bilirubin concentration was not an important discriminator of encephalopathy.