AUTORADIOGRAPHIC MAPPING OF LOCAL CEREBRAL PERMEABILITY TO BILIRUBIN IN IMMATURE RATS - EFFECTS OF HYPERBILIRUBINEMIA

Kernicterus is characterized by the accumulation of bilirubin mainly i nto subcortical brainstem nuclei. Inasmuch as premature infants are mo re susceptible to kernicterus, we hypothesized that the cerebral perme ability to bilirubin could vary by cerebral region and with age. There fore, in the present study, we measured the blood-to-brain transfer co nstant (K-i) of [H-3]bilirubin in 6-8 rats at postnatal age 10 (P10) o r 21 d (P21) in basal conditions and after a bilirubin perfusion to ex plore age-related and bilirubin-induced changes in the cerebral permea bility to the dye. Blood-to-brain transfer of [H-3]bilirubin was measu red in 39 brain regions by quantitative autoradiography in 15-min expe riments. Rats exposed to unlabeled bilirubin received a loading dose o f 160 mg/kg over 15 min followed by a 90-min bilirubin perfusion at a speed of 64 mg/kg/h. At P10, cerebral permeability to bilirubin ranged from 0.07 to 0.12 mu L/g/min, except in the auditory nerve, dentate n ucleus, hypothalamus, and thalamus where it reached 0.41-0.47 mu L/g/m in. At P21, K, of bilirubin was significantly lower than at P10 and ra nged from 0.03-0.06 mu L/g/min in most brain areas. In P10 bilirubin-e xposed rats, permeability to bilirubin significantly increased over co ntrol levels in all brain regions but three. The largest increases (>3 50%) were recorded in the sensory regions, most limbic areas, hypothal amus, and thalamus. At P21, hyperbilirubinemia induced increases in bl ood-to-brain transfer of bilirubin of 50-200% in 16 brain areas, excep t in the hippocampus, sensory-motor cortex, and thalamic nuclei where they reached 200-433%. Thus, it appears that the immature mt brain (P1 0) is very permeable to bilirubin. The increased permeability with pre exposure to the dye, especially in brain regions which are affected in infants with kernicterus, could be related either to the large decrea se in the value of the albumin:bilirubin ratio between control (15-16) and hyperbilirubinemic conditions (1.7-1.8) and/or to an increased pe rmeability to bilirubin.