{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:22:46Z","timestamp":1787026966472,"version":"build-2736575974"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Stereotactic radiosurgery (SRS) is widely used to treat vestibular schwannomas but may cause irreversible hearing loss due to cochlear toxicity. The underlying mechanisms are not fully understood, and no effective otoprotective therapies exist. We aimed to establish a mouse model that replicates the clinical pattern of radiation-induced hearing loss.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      C57BL\/6J mice (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f31) received 8\u202fGy (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f3), 16\u202fGy (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f5), 24\u202fGy (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f8), or 32\u202fGy (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f15) using the Leksell Gamma Knife ICON system. Targeting was based on the built-in cone-beam CT, co-registered with MRI and CT-based mouse atlases, to guide unilateral cochlea targeting. A single isocenter was placed lateral to the right cochlea, with the 80% isodose line traversing its medial edge. Auditory brainstem response (ABR) was measured at baseline and at 1 and 4\u202fweeks post-SRS. A 32\u202fGy subgroup (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f7) was evaluated at 16\u202fweeks. Histological analysis of cochleae was performed at 4\u202fweeks in all groups and at 16\u202fweeks in the long-term 32\u202fGy group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SRS was well tolerated, and the contralateral cochlea received a very low radiation dose. No ABR shifts were observed at 8 or 16\u202fGy, with only minimal histological changes. At 32\u202fGy, ABR threshold shifts at 22.6 and 32\u202fkHz were evident by week 1 and worsened by week 4. Similar but milder effects occurred at 24\u202fGy. In the 32\u202fGy long-term subgroup, hearing loss progressed across all frequencies, most severely at high frequencies, alongside a sustained wave I amplitude decline. At 32\u202fGy, outer hair cells were reduced by 14 and 44% at 32 and 45.2\u202fkHz, respectively, at 4\u202fweeks, and by 38 and 80% at 16\u202fweeks. Ribbon synapses were mildly reduced at 4\u202fweeks and more markedly at 16\u202fweeks in corresponding high-frequency regions. Spiral ganglion neuron density was mildly reduced at the basal and middle turns. All reported changes were statistically significant when compared to the contralateral ear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This new model reproduces key features of SRS-induced cochlear toxicity, including unilateral, dose-dependent, and progressive hearing loss. It thus provides a valuable platform for investigating mechanisms and testing otoprotective strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnins.2026.1748309","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T04:55:31Z","timestamp":1778129731000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Introducing a translationally relevant mouse model of radiosurgery-induced unilateral hearing loss"],"prefix":"10.3389","volume":"20","author":[{"given":"Dimitrios","family":"Daskalou","sequence":"first","affiliation":[{"name":"The Inner Ear and Olfaction Lab, Faculty of Medicine, University of Geneva","place":["Geneva, Switzerland"]},{"name":"Service of Otorhinolaryngology-Head and Neck Surgery, Department of Clinical Neurosciences, Geneva University Hospitals","place":["Geneva, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Rousset","sequence":"additional","affiliation":[{"name":"The Inner Ear and Olfaction Lab, Faculty of Medicine, University of Geneva","place":["Geneva, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Sgroi","sequence":"additional","affiliation":[{"name":"The Inner Ear and Olfaction Lab, Faculty of Medicine, University of Geneva","place":["Geneva, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"Oberhauser","sequence":"additional","affiliation":[{"name":"The Inner Ear and Olfaction Lab, Faculty of Medicine, University of Geneva","place":["Geneva, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Philippe","family":"Thiran","sequence":"additional","affiliation":[{"name":"Laboratory of Signal Processing 5, \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne (EPFL)","place":["Lausanne, Switzerland"]},{"name":"Department of Radiology, Lausanne University Hospital (CHUV)","place":["Lausanne, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantin","family":"Tuleasca","sequence":"additional","affiliation":[{"name":"Neurosurgery Service and Gamma Knife Center, Centre Hospitalier Universitaire Vaudois (CHUV)","place":["Lausanne, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ileana O","family":"Jelescu","sequence":"additional","affiliation":[{"name":"Department of Radiology, Lausanne University Hospital (CHUV)","place":["Lausanne, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Levivier","sequence":"additional","affiliation":[{"name":"Neurosurgery Service and Gamma Knife Center, Centre Hospitalier Universitaire Vaudois (CHUV)","place":["Lausanne, Switzerland"]},{"name":"H\u00f4pital de La Tour, Centre NeuroKnife","place":["Geneva, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Senn","sequence":"additional","affiliation":[{"name":"The Inner Ear and Olfaction Lab, Faculty of Medicine, University of Geneva","place":["Geneva, Switzerland"]},{"name":"Service of Otorhinolaryngology-Head and Neck Surgery, Department of Clinical Neurosciences, Geneva University Hospitals","place":["Geneva, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,7]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1227\/neu.0000000000002354","article-title":"Long-term hearing outcome after radiosurgery for vestibular schwannoma: a systematic review and meta-analysis","volume":"92","author":"Balossier","year":"2023","journal-title":"Neurosurgery"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"16878","DOI":"10.1038\/s41598-017-17204-5","article-title":"QuPath: open source software for digital pathology image analysis","volume":"7","author":"Bankhead","year":"2017","journal-title":"Sci. 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