The effects of brain bilirubin deposition on auditory brain stem evoked responses in rats

Auditory brain stem evoked responses (ABR) in newborn infants are altered by elevated serum bilirubin levels and may be used as an indicator of bilirubin toxicity. The hypothesis of our study was that hyperbilirubinemia may affect ABR's because of bilirubin deposition in the brain stem. We examined this hypothesis by studying 21 male adult rats divided into three groups: group A, control (n = 8); group B, low bilirubin (n = 6); and group C, high bilirubin (n = 7). Each experimental group was studied over 150 min. The control group received a buffer solution. The low bilirubin group received a low dose bilirubin bolus of 50 mg/kg followed by continuous infusion of 20 mg/kg/h. The high bilirubin group received a bolus of 100 mg/kg bilirubin followed by continuous infusion of 40 mg/kg/h. All groups received sulfisoxazole (50 mg/kg X 3) during the second hour of the study. Auditory evoked potentials were recorded at 0 and 150 min. At the end of the study, the brains were analyzed for bilirubin content. Bilirubin deposition in the 3 groups was 0.6 +/- 0.28 micrograms/g, 0.93 +/- 0.07 micrograms/g and 3.2 +/- 2.2 micrograms/g for the control, low bilirubin and high bilirubin groups, respectively. Bilirubin deposition in the brain was associated with a significant amplitude reduction of Wave I and III, but had no effect on absolute latencies and interpeak latencies. Very high brain bilirubin concentrations were associated with absence of Waves I and IV. Wave I was also significantly reduced in the low bilirubin group where there was slightly increased bilirubin deposition in the brain. We conclude that ABR changes in the form of wave amplitude reduction were associated with brain stem and cerebellum bilirubin deposition. We speculate that previously reported observations of abnormal ABR changes in hyperbilirubinemic newborn infants are associated with bilirubin deposition.