REGIONAL CEREBRAL METABOLIC CONSEQUENCES OF BILIRUBIN IN RAT DEPEND UPON POST-GESTATIONAL AGE AT THE TIME OF HYPERBILIRUBINEMIA

While the accumulation of bilirubin in specific brain regions has been well characterized at autopsy in kernicteric infants, data on the regional effects of early cerebral bilirubin intoxication are still missing. Therefore, the quantitative autoradiographic [C-14]2-deoxyglucose technique was applied to the measurement of the effects of a bilirubin infusion on local cerebral metabolic rates for glucose (LCMRglc) in immature rats. A loading dose of 80 mg/kg bilirubin was first administered to the animals over 15 min. Thereafter, the velocity of the infusion was reduced to 32 mg/kg/h and the infusion was continued for 105 min. The animals were studied at two ages, postnatal day 10 (P10) and P21. The [C-14]2-deoxyglucose was injected to the animals 45 min before the end of the infusion. Bilirubin infusion led to plasma concentrations ranging from 100 to 200 mu mol/l at both ages and to brain amounts of 10-16 nmol/g at P10 while bilirubin was not detectable in brain at P21. Hyperbilirubinemia induced widespread decreases in LCMRglcs at P10 and had rather limited consequences on cerebral glucose utilization at P21. At P10, decreases in LCMRglcs were mostly prominent in regions that have been shown to preferentially accumulate bilirubin in kernicteric infants. In conclusion, there appears to be a good correlation between these metabolic data and regional brain permeability to bilirubin.