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 b etween the areas which appear to preferentially accumulate bilirubin a nd regional changes in cerebral functional activity. Therefore, we app lied the quantitative autoradiographic [C-14]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 1 60 mg/kg bilirubin in a buffered serum albumin solution was first give n to the rats over 15 min. Thereafter, bilirubin was infused at a redu ced rate, 64 mg/kg/h. Bilirubin infusion lasted from 2 to 3 h accordin g 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 per iod. Bilirubin entered the brain without any sign of blood-brain barri er alteration. The [C-14]2-deoxyglucose was injected to the animals 45 min before the end of bilirubin infusion. Rats were studied at 3 post natal ages, 10 (P10), 14 (P14) and 21 days (P21). Hyperbilirubinemia i nduced widespread decreases in LCMRglc's in all brain areas and at all ages. These decreases were mostly prominent in sensory areas, auditor y and visual, as well as in hypothalamic and thalamic regions. Especia lly at P10, the distribution of LCMRglc's was strikingly heterogeneous in both cerebral cortex and caudate nucleus, appearing as alternate d ark and white columns or as alternate dark and light dots, respectivel y. The data of the present study are in agreement with clinical observ ations 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.