Development of brainstem auditory evoked potentials in heterozygous and homozygous jaundiced Gunn rats

Bilirubin toxicity is a significant clinical problem causing neurologic and audiologic sequelae. To better understand the pathogenesis of bilirubin toxicity in the immature nervous system we studied the development of brainstem auditory evoked potentials (BAEPs) in jaundiced (jj) Gunn rats and their non-jaundiced (Jj) littermates. Littermate pairs of Jj and jj rats were studied serially from early infancy to adulthood. Replicated BAEPs to click stimuli at two different intensities (45 and 75 dB SPL) and rates (33 and 89/s) were obtained from animals anesthetized with ketamine and acepromazine and maintained at a constant rectal temperature. Jaundiced (jj) rats had increased latencies of waves II and III and the I-II and I-III intervals, and decreased amplitudes of waves II and III from 17 days of age through adulthood. For both groups, all latencies and interwave intervals decreased with age (P less than 0.0001 for each wave and interwave interval by repeated measures ANOVA), and the amplitude of II increased with age (P less than 0.0001). No group differences were found in wave I latency or amplitude, or in the latency change of waves I, II or III as a function of intensity (about 11 microseconds/dB at all ages), suggesting that peripheral auditory function is normal in jj rats. Finally, there were no different effects of stimulation rate on BAEP wave latencies between groups. The findings suggest dysfunction of the central (brainstem) auditory pathways at and rostral to the cochlear nuclei, and are consistent with studies showing destruction of the cochlear nuclei in this animal model and in humans with bilirubin toxicity. The central abnormalities previously found in adult, jaundiced rats are now demonstrated in animals as early as 17 days of age, when serum bilirubin concentration is maximum. The BAEP findings are similar to changes found in hyperbilirubinemic human neonates, and support the use of the Gunn rat animal model for the study of bilirubin encephalopathy.