title: Blood-brain barrier permeability to bilirubin in the rat studied using intracarotid bolus injection and in situ brain perfusion techniques.
abstract: 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.
authors.affiliation: Department of Paediatrics, School of Medicine, University College London, Rayne Institute, United Kingdom.
authors.forename: N K
authors.initials: NK
authors.lastname: Ives
authors.forename: R M
authors.initials: RM
authors.lastname: Gardiner
mesh_terms: D000818:Animals; D001663:Bilirubin / Q000493:pharmacokinetics*; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000378:metabolism; D002250:Carbon Radioisotopes; D002463:Cell Membrane Permeability; D008297:Male; D010477:Perfusion; D010539:Permeability; D051381:Rats; D011919:Rats, Inbred Strains; D014316:Tritium
chemical_list: D002250:Carbon Radioisotopes; D014316:Tritium; D001663:Bilirubin