The Jaundiced Gunn Rat Model of Auditory Neuropathy/Dyssynchrony

OBJECTIVE: High levels of bilirubin are neurotoxic and may result in deafness or auditory neuropathy/auditory dyssynchrony (AN/AD). The jaundiced (jj) Gunn rat animal model of kernicterus has electrophysiologic and neuroanatomic abnormalities of brainstem auditory nuclei with normal cochlear microphonic recordings. We examined morphologic changes in the cochlea, spiral ganglion, and auditory nerve and relate these findings to current understanding of AN/AD. METHODS: At 15 days of age, jj and nonjaundiced (Nj) littermates were injected with sulfadimethoxine (sulfa) and killed 3 days later by transcardial perfusion. Sections were cut through decalcified temporal bones, cochlear nerves, and auditory brainstem and processed for light and electron microscopy and immunohistochemical localization of calbindin-D and parvalbumin. RESULTS: Spiral ganglion neurons were severely degenerated with a paucity of myelinated axons in jj animals. Electron microscopy of the intramodilar auditory nerve revealed a lack of large caliber axons in jj-sulfa versus Nj-sulfa controls. Large diameter degenerating axons were characterized by an electron-dense atrophied axis cylinder resembling an axonopathy. CONCLUSIONS: Our findings of abnormal spiral ganglion cells and selective loss of large, myelinated auditory nerve fibers with no abnormalities in cochlear hair cells, support the sulfa-treated jj Gunn rat as a model for bilirubin induced AN/AD. The paucity of large caliber neurons undermines temporal coding of auditory information and neural synchrony and demonstrates that in addition to brainstem auditory nuclei, spiral ganglion neurons are selectively vulnerable to bilirubin toxicity.