Abstract 1307 Poster Session II, Sunday, 5/2 (poster 50)

Sensorineural hearing loss and auditory processing disturbances have been associated with elevated levels of bilirubin. Both cochlear and retrocochlear sites have been implicated in the etiology of auditory dysfunction resulting from neonatal hyperbilirubinemia. In previous studies, we have demonstrated a substantial reduction in the density of immunoreactive staining for the calcium-binding proteins (CaBPs), calbindin-D28k and parvalbumin, in the dorsal and ventral cochlear nuclei and the superior olivary complex in the homozygous, jaundiced Gunn rat in comparison to non-jaundiced, heterozygous littermate control rats. The findings from these studies demonstrated that bilirubin toxicity in the auditory brainstem in the absence of kernicteric lesions produces molecular changes in the expression of CaBPs in the brainstem auditory nuclei that correlate well with electrophysiological deficits in the brainstem auditory-evoked potentials and the retrocochlear sensorineural hearing loss that characterize bilirubin toxicity.

The present study was undertaken to determine whether these changes in the immunoreactivity toward CaBPs are the result of a direct effect of bilirubin in the brainstem or reflect a cascade of pathological events originating in the cochlea. In non-jaundiced Gunn and normal Wistar rats, both inner and outer hair cells in the cochlea are immunoreactive toward both CaBPs with a decreasing gradient extending from the apex (representing low frequency) to the base (representing high frequency). Many neurons in the spiral ganglion also are immunoreactive to the CaBPs. In jaundiced Gunn rats, both the density and pattern of immunoreactive staining of the inner and outer hair cells and spiral ganglion neurons in the cochlea are comparable to the non-jaundiced animals. However, in the brainstem of the same jaundiced animals, the superior olivary complex and cochlear nuclei exhibit a marked decrease in immunoreactive labeling for the CaBPs. These findings suggest that bilirubin toxicity impairs the calcium homeostasis of specific populations of brainstem auditory neurons while sparing the cochlea. However, the possibility of direct effects on the eighth nerve (e.g., auditory neuropathy) currently cannot be eliminated.

Supported by grants from the American Hearing Research Foundation and the National Institutes of Health (EY02191 and DC00369)