Blood-brain barrier permeability to bilirubin in the rat studied using intracarotid bolus injection and in situ brain perfusion techniques.
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.
Ives
N K
NK
Department of Paediatrics, School of Medicine, University College London, Rayne Institute, United Kingdom.
Gardiner
R M
RM
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
D002250:Carbon Radioisotopes; D014316:Tritium; D001663:Bilirubin