Sex-specific regional brain bilirubin content in hyperbilirubinemic Gunn rat pups.
BACKGROUND
The hyperbilirubinemic j/j Gunn rat is frequently used to study the effects of neonatal hyperbilirubinemia on the developing central nervous system (CNS). Despite evidence that the cerebellar region and males are predisposed to bilirubin-induced brain injury in this animal model, there are limited regional and no sex-specific brain bilirubin content data.


OBJECTIVE
To characterize and contrast the regional (cortex, brainstem, cerebellum) and sex-specific CNS bilirubin contents of hyperbilirubinemic j/j Gunn rat pups and their age-matched (15-19 days) nonjaundiced J/j counterparts. Pups were injected 24 h prior to sacrifice with sulfadimethoxine (200 mg/kg i.p.) to enhance the CNS bilirubin content.


RESULTS
The CNS bilirubin contents in each region and total serum bilirubin levels were significantly greater in jaundiced j/j pups versus nonjaundiced J/j pups. Within the sulfadimethoxine-treated male j/j cohort, the mean brain bilirubin content was highest in the cerebellum (18.9 +/- 7.8 microg/g), intermediate in the brainstem (10.7 +/- 8.0 microg/g), and lowest in the cortex (4.7 +/- 3.0 microg/g) (F = 11.31, p < 0.001 by ANOVA), and the cerebellar bilirubin level was significantly higher than in the littermate-matched sulfadimthoxine-treated j/j female pups (p < 0.02). The serum albumin levels were not different between j/j male and j/j female pups.


CONCLUSIONS
We conclude that the brain bilirubin content of hyperbilirubinemic j/j Gunn rat pups is greater than in nonjaundiced J/j pups and varies as a function of CNS region and sex. We speculate that the higher cerebellar bilirubin content may preferentially predispose male j/j Gunn rat pups to bilirubin-induced neurotoxicity.
Division of Newborn Medicine, Department of Pediatrics, Magee-Women's Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Carrie
C
Cannon
Monica J
MJ
Daood
Terrence L
TL
O'Day
Jon F
JF
Watchko
D000818:Animals; D001663:Bilirubin / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D005260:Female; D006932:Hyperbilirubinemia / Q000378:metabolism*; D008297:Male; D051381:Rats; D011911:Rats, Gunn / Q000502:physiology*; D012727:Sex Characteristics
D001663:Bilirubin