Experimental bilirubin encephalopathy. The mode of entry of bilirubin-14C into the central nervous system.

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Abstract
Experiments were conducted in animals to study the effect of altered bilirubin-binding properties of the plasma on pigment level in the brain. In newborn guinea pigs and adult Gunn rats, bilirubin-C14 was infused either bound to human albumin or dissolved in aqueous taurocholate or guinea pig serum. Administration of unbound bilirubin-C14 resulted in lower serum concentrations and higher brain levels of radioactivity than when the pigment was given bound to human albumin; C14-bilirubin deposited in the brain by infusion of unbound pigment could in part be mobilized and returned to the circulation by treatment with human albumin; salicylate competitively displaced biliruhin from plasma albumin binding sites and enhanced accumulation of the pigment in the brain; and induction of acidosis increased the extravascular distribution of C14-bilirubin, including the brain. In newborn guinea pigs increased bilirubin concentration in the brain frequently was associated with severe neurologic damage and reduced viability. In animals infused with unbound pigment, survival was substantially increased by subsequent treatment with human albumin, despite higher serum bilirubin levels produced by the albumin infusions. These findings indicate that only unbound bilirubin can cross the blood-brain barrier. Consequently, the amount of bilirubin transferred into the brain is determined by the magnitude of the unbound pigment fraction rather than by the total pigment concentration of the plasma. The study provides direct experimental support for the proposed use of albumin in the prevention and treatment of bilirubin encephalopathy in neonatal hyperbilirubinemia, alone or in association with exchange transfusion. It also demonstrates the importance of early correction of acidosis and the deleterious effect of compounds that may displace bilirubin from albumin.