Effects of bilirubin infusion on local cerebral glucose utilization in the immature rat

The clinical features of kernicterus have been extensively described. However, there are still no data available on a possible correlation between the areas which appear to preferentially accumulate bilirubin and regional changes in cerebral functional activity. Therefore, we applied the quantitative autoradiographic [14C]2-deoxyglucose method to the measurement of local cerebral metabolic rates for glucose (LCMRglc) in immature rats receiving a bilirubin infusion. A loading dose of 160 mg/kg bilirubin in a buffered serum albumin solution was first given to the rats over 15 min. Thereafter, bilirubin was infused at a reduced rate, 64 mg/kg/h. Bilirubin infusion lasted from 2 to 3 h according to the age of the animal, in order to obtain a plasma concentration of bilirubin ranging from 200 to 300 mumol/l over the experimental period. Bilirubin entered the brain without any sign of blood-brain barrier alteration. The [14C]2-deoxyglucose was injected to the animals 45 min before the end of bilirubin infusion. Rats were studied at 3 postnatal ages, 10 (P10), 14 (P14) and 21 days (P21). Hyperbilirubinemia induced widespread decreases in LCMRglc's in all brain areas and at all ages. These decreases were mostly prominent in sensory areas, auditory and visual, as well as in hypothalamic and thalamic regions. Especially at P10, the distribution of LCMRglc's was strikingly heterogeneous in both cerebral cortex and caudate nucleus, appearing as alternate dark and white columns or as alternate dark and light dots, respectively. The data of the present study are in agreement with clinical observations reporting that bilirubin mostly accumulates in the striatum and cranial nerves and that the neurological sequelae of kernicterus are very often hearing loss as well as motor problems.