The Importance of Serum Binding and the Blood Brain Barrier in the Development of Acute Bilirubin Neurotoxicity
Several recent studies have created considerable confusion about the cause and prevention of kernicterus.1,2,3 In 1982, Levine et al1 demonstrated in rats that “kernicterus” could be produced by osmotic opening of the blood brain barrier. Using a technique described by Rapoport et al,4 a hypertonic solution of arabinose was infused into one carotid artery, producing a temporary osmotically induced disruption of the blood brain barrier in the ipsilateral hemisphere. Subsequent intravenous infusion of bilirubin resulted in yellow staining of the affected region. Levine proposed that movement of albumin bound bilirubin across a disrupted barrier was the principal cause of kernicterus, and presented this as “an alternative hypothesis” to the “free bilirubin theory.” However, he provided no evidence that the yellow staining produced brain damage, either by histological examination or behavioral consequences. These observations, together with other studies which failed to confirm any predictive indices for kernicterus in premature infants,2,3 prompted Lucey5 to editorialize that current concepts of the pathogenesis of kernicterus should be abandoned in search for a “more attractive hypothesis.”
KeywordsHuman Serum Albumin Bilirubin Concentration Ipsilateral Hemisphere Neonatal Jaundice Serum Bilirubin Concentration
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