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Sex-specific regional brain bilirubin content in hyperbilirubinemic Gunn rat pups
Carrie Cannon1, Monica J Daood, Terrence L O'Day
1Division of Newborn Medicine, Department of Pediatrics, Magee-Women's Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Insights
Neonatal hyperbilirubinemia in j/j Gunn rats shows higher brain bilirubin in males, particularly in the cerebellum. This regional and sex-specific difference may increase neurotoxicity risk in male pups.
Area of Science:
- Neuroscience
- Toxicology
- Developmental Biology
Background:
- The j/j Gunn rat model is crucial for studying neonatal hyperbilirubinemia's impact on the central nervous system (CNS).
- Previous research suggests males and the cerebellum are susceptible to bilirubin-induced brain injury.
- Limited regional and sex-specific data on brain bilirubin content exist.
Purpose of the Study:
- To quantify and compare regional (cortex, brainstem, cerebellum) and sex-specific CNS bilirubin levels.
- To investigate bilirubin distribution in hyperbilirubinemic j/j Gunn rat pups versus nonjaundiced controls.
- To utilize sulfadimethoxine to enhance CNS bilirubin accumulation for analysis.
Main Methods:
- Hyperbilirubinemic j/j Gunn rat pups and nonjaundiced J/j controls (15-19 days old) were used.
- Sulfadimethoxine was administered 24 hours prior to sacrifice to increase CNS bilirubin.
- Bilirubin content was measured regionally within the cortex, brainstem, and cerebellum.
Main Results:
- Jaundiced j/j pups exhibited significantly higher CNS bilirubin and serum bilirubin levels than nonjaundiced J/j pups.
- In male j/j pups, cerebellar bilirubin content was highest, followed by the brainstem, then the cortex.
- Cerebellar bilirubin levels were significantly higher in males compared to female j/j pups, with no difference in serum albumin.
Conclusions:
- Brain bilirubin content in j/j Gunn rat pups is elevated compared to controls and varies by CNS region and sex.
- Higher cerebellar bilirubin concentrations in male j/j pups may indicate a greater predisposition to bilirubin-induced neurotoxicity.
- These findings highlight regional and sex-specific vulnerabilities in the developing brain to hyperbilirubinemia.
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/Methods:
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.
