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It has generally been assumed that free unconjugated bilirubin gains access to the brain because of its lipid solubility. However, no measurements of the blood-brain barrier permeability to free bilirubin exist. The aim of these experiments was to determine the blood-brain barrier permeability in the rat to free bilirubin using single-pass (Oldendorf) and in situ perfusion (Takasato) techniques. Studies were performed on adult rats under sodium pentobarbitone anesthesia. [3H]bilirubin IX-alpha-ZZ (sp act 6.2 Ci/mmol) was synthesized by reduction of biliverdin with sodium boro-[3H]hydride. Blood-brain barrier permeability to albumin-bound and free bilirubin was determined using injectates/perfusates containing a molar excess of human serum albumin with or without the addition of the displacing agent sulphadimethoxine. For free bilirubin, the brain uptake index was 28.5 +/- 9.3 (mean +/- SD, n = 18), and the permeability surface area product was 54.84 +/- 36.38 x 10(-4) mL/s/g (mean +/- SD, n = 13). These results demonstrate that the behavior of free bilirubin in vivo in relation to the cerebral microvasculature corresponds to that of a "lipid soluble" molecule.

Blood-Brain Barrier Permeability to Bilirubin in the Rat Studied Using Intracarotid Bolus Injection and in Situ Brain Perfusion Techniques