Auditory Effects of Cranial Irradiation in a Mouse Model

Abstract

Objective: 1) Determine whether radiation exposure in mice leads to measurable hearing losses similar to those seen in patients exposed to radiotherapy for acoustic neuromas, temporal bone malignancies, and nasopharyngeal carcinoma. 2) Assess for any associated pathologic changes in cochleas exposed to radiation. Method: Adult (11-13 weeks) 129Sv/J mice were exposed to radiation using an animal irradiator, ranging from a single exposure of 10 Gy to 100 Gy. Pre- and postradiation audiometric brainstem response (ABR) data were recorded to document hearing loss, with subsequent analysis of cochlear ultrastructure using transmission and scanning electron microscopy. Results: High-frequency hearing loss was noted in exposures exceeding 40 Gy. Anorexia was observed by day 6 post- irradiation in all mice exposed to doses ≥20 Gy. Normal hearing following 20 Gy exposure suggests that hearing losses seen after ≥40 Gy exposures is secondary to radiation effects rather than any confounding metabolic disturbance. Ultrastructural analysis revealed dramatically decreased neuron density in Rosenthal’s canal and loss of the associated extracellular matrix. Negligible changes were seen in the outer and inner hair cells, with overall preservation of the stria vascularis and cochlear vasculature. Age-matched controls failed to demonstrate similar histopathologic findings. Conclusion: This study demonstrates that the mouse is a viable model for the study of radiation-induced hearing loss. The initial impact of the radiation appears to focus on the eighth nerve cell body and the axonal projections to the organ of Corti. Future studies should incorporate fractionation of the radiation dose.