Bilirubin is a product of heme catabolism which by virtue of its lipid solu
bility can cross the blood-brain barrier and enter the brain. Neonatal jaun
dice is a common transitional phenomenon which is due to the combination of
increased heme catabolism and rate limitations as far as hepatic conjugati
on and biliary excretion of bilirubin, In the great majority of cases this
is an innocuous condition, which is even posited to have some beneficial ef
fects due to the ability of bilirubin to quench free oxygen radicals. Howev
er, because bilirubin is neurotoxic, hyperbilirubinemia in the newborn may
exceptionally result in death in the neonatal period, or survival with seve
re neurological sequelae (kernicterus). Bilirubin enters the brain through
an intact blood-brain barrier, Clearance of bilirubin from brain partly inv
olves retro-transfer through the blood-brain barrier, and possibly also thr
ough the brain-CSF barrier into CSF. Work in our lab during the past 5 year
s has substantiated earlier work which had suggested that bilirubin may als
o be metabolized in brain, The responsible enzyme is found on the inner mit
ochondrial membrane, and oxidizes bilirubin at a rate of 100-300 pmol bilir
u-bin/mg protein/minute. The enzyme activity is lower in the newborn compar
ed with the mature animal, and is also lower in neurons compared with glia.
Studies of different rat strains have documented genetic variability. The
enzyme is cytochrome-c-dependent, but has as yet not been unequivocally ide
ntified. The rate of oxidation of bilirubin is such that this enzyme probab
ly contributes meaningfully to the clearance of bilirubin from brain. (C) 2
000 Academic Press.