A new rat model of neonatal bilirubin encephalopathy (kernicterus)

IntroductionHemolytic kernicterus, an indirect bilirubin-induced brain dysfunction, is associated with hyper-bilirubinemia in mammalian neonates. In this study, a new model of kernicterus has been developed using intra-peritoneal injections of phenyl hydrazine and subcutaneous injections of sulfisoxazole. These drugs can potentially induce kernicterus in neonatal through changes in hemolysis and hypo-albumin.MethodsFor this purpose, 7-day-old male Wistar rats (n = 72; mean weight 11 ± 1 g) were used. The animals have been divided into six different groups which received the drugs alone and their combination, and the drugs' solvents and their combination. Biochemical parameters, brain iron and bilirubin, behavioural performance, auditory function and apoptosis were measured using auto-analyser instruments; atomic absorption spectroscopy, Sawasaki, footprint, auditory brainstem response (ABR) and TUNEL test, respectively.ResultThe drug-injected groups showed a significant reduction in serum haematocrit and an increase in the concentration of brain bilirubin, total and indirect bilirubin as well as TUNEL positive cells in basal ganglia. In addition, the obtained results showed that there was a significant increase in behavioural disturbance and auditory dysfunction in the group injected with the combination of two drugs.ConclusionThis kernicterus-induced rat model could perfectly mimic the common conditions of the hyperbilirubinemia in human neonates. This study offers an easy technique to develop more stable models for follow-up studies.