A mouse model of unilateral stereotactic radiosurgery-induced hearing loss.

Introduction: Stereotactic radiosurgery (SRS) is a precise, single-session irradiation technique commonly used to treat vestibular schwannomas. However, SRS can lead to irreversible hearing loss, most probably due to irradiation-induced damage to the nearby inner ear. Currently, no preventive or therapeutic options exist, highlighting the need for the development and experimental testing of novel treatments. To enable this research, we developed a protocol for inducing unilateral hearing loss in mice through targeted unilateral cochlear irradiation. Material and methods: We used 6-week-old C57BL/6J mice and administered precise unilateral irradiation in the vicinity of the cochlea using a Leksell Gamma Knife® Icon device. The precision and reproducibility of the targeted area were ensured through radiological imaging for each mouse using the integrated cone beam CT scan and co-registering these images with MRI and CT mouse atlas images. To ensure meaningful translational data, we placed a single 4 mm isocenter lateral to the cochlea with the 80% isodose line passing through the modiolus to deliver 8 (n = 3), 16 (n = 5), 24 (n = 8), and 32 (n = 8) Gy. Auditory brainstem responses (ABR) were measured one day prior to irradiation (baseline) and at one and four weeks post-irradiation. Statistical analysis was performed using two-way repeated measures ANOVA with Bonferroni correction. Results: In all experimental groups, the irradiation dose received by the non-irradiated cochlea was less than 15% of that received by the irradiated cochlea. In the 32 Gy group, irradiation of cochlea yielded significant threshold shifts, compared to the non-irradiated ear, at 22.6 and 32 kHz on day 7 and to a greater degree on day 28. Similar but less pronounced effects were observed in the 24 Gy group. Furthermore, we observed a unilateral decrease in the p-p and wave I amplitudes, following 72-78 dB SPL click stimulation, in both groups. No hearing loss was detected in the 8 and 16 Gy groups. Histopathological studies are ongoing. Conclusions: Targeted near-cochlear irradiation in mice induces unilateral dose-dependent high-frequency hearing loss, evidenced by increased threshold shifts and decreased ABR wave I amplitudes. This model provides a valuable tool for exploring the radiobiological mechanisms underlying SRS-induced hearing loss and for testing potential radioprotec-tive agents. [ABSTRACT FROM AUTHOR]