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.