Experimental bilirubin encephalopathy: importance of total bilirubin, protein binding, and blood-brain barrier.
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.
D000818:Animals; D001663:Bilirubin / Q000633:toxicity*; D001812:Blood-Brain Barrier; D001927:Brain Diseases / Q000209:etiology* / Q000503:physiopathology; D004569:Electroencephalography; D006932:Hyperbilirubinemia / Q000150:complications* / Q000503:physiopathology; D008297:Male; D011485:Protein Binding; D051381:Rats; D012709:Serum Albumin / Q000378:metabolism
D012709:Serum Albumin; D001663:Bilirubin