RATES OF BILIRUBIN CLEARANCE FROM RAT-BRAIN REGIONS

The mechanism for the preferential distribution of bilirubin to basal ganglia ('kernicterus') is unknown. We hypothesized that differences in bilirubin clearance rates between brain regions might explain this phenomenon. Bilirubin [30 mg/kg over 5 min, with 370-740 kBq (10-20 mu Ci) tritiated bilirubin] was infused into a peripheral vein in unanesthetized, young Sprague-Dawley rats (n = 36, weight 149 +/- 15 g, mean +/- SD). After blood sampling, groups of rats were killed at 15, 30, 45, 60, 75, 180, and 360 min with an intravenous injection of pentobarbital. Brain vasculature was flushed in situ and brains dissected into seven regions, which were weighed, dissolved and scintillation counted. Blood was analyzed for bilirubin, albumin, and blood gases. Brain bilirubin concentrations were calculated after determining the specific activity of bilirubin in serum at the time of sacrifice. Bilirubin half-lives in serum and brain regions were (in minutes, mean +/- SD): serum 24.6 +/- 17.2, whole brain 18.5 +/- 21.5, cortex 17.6 +/- 19.3, hippocampus 19.0 +/- 21.5, striatum 17.1 +/- 18.5, midbrain 16.3 +/- 18.6, hypothalamus 17.4 +/- 21.0, cerebellum 21.6 +/- 33.8, medulla 20.0 +/- 24.1. There were no significant differences in bilirubin half-lives between regions. The half-life of bilirubin in brain reported here is appreciably shorter than the 1.7 h previously found in rats with opened blood-brain barriers, but appears compatible with data on auditory brainstem response reversibility following exchange transfusion in jaundiced infants. We conclude that bilirubin disappeares rapidly from brains with intact blood-brain barriers. The rates of clearance found in different brain regions in this model cannot explain the kernicterus phenomenon (i.e. preferential staining of basal ganglia and cerebellum).