Dexamethasone’s Effect in the Retrocochlear Auditory Centers of a Noise-Induced Hearing Loss Mouse Model

• Published in: Otolaryngology-head and neck surgery 2014-10, Vol.151 (4), p.667-674
• Main Authors: Chen, Leon, Dean, Clare, Gandolfi, Michele, Nahm, Edmund, Mattiace, Linda, Kim, Ana H.
• Format: Article
• Language: English
• Subjects: Animals; Cochlear Nucleus - drug effects; Cochlear Nucleus - pathology; dexamethasone; Dexamethasone - therapeutic use; Disease Models, Animal; Evoked Potentials, Auditory, Brain Stem - drug effects; Glucocorticoids - therapeutic use; Hair Cells, Auditory - drug effects; Hair Cells, Auditory - pathology; Hearing Loss, Noise-Induced - pathology; Hearing Loss, Noise-Induced - prevention & control; Male; Mice; Mice, Inbred CBA; noise‐induced hearing loss; Otoacoustic Emissions, Spontaneous - drug effects; retrocochlear; Superior Olivary Complex - drug effects; Superior Olivary Complex - pathology
• ISSN: 0194-5998; 1097-6817
• DOI: 10.1177/0194599814545771

Objective Examine prophylactic effects of dexamethasone (Dex) in retrocochlear auditory centers in a noise-induced hearing loss (NIHL) mouse model. Study Design Prospective animal study. Setting Academic research center. Subjects and Methods Thirty-two mice were divided into control, untreated, saline (2 and 10 µL), and Dex (2 and 10 µL) groups. Dex was applied intratympanically (IT) prior to 110 to 120 dB noise over 6 hours. Auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) were performed at 1 day, 1 week, 1 month, and 2 months. Retrocochlear neuronal cells were labeled with FluoroGold and counted. Hair cells of the organ of Corti were labeled with fluorescein isothiocyanate-conjugated phalloidin and counted. Results Auditory brainstem response thresholds of untreated NIHL, 2 and 10 µL IT saline, and 2 and 10 µL IT Dex were 21.7 ± 2.9 dB, 20 ± 0 dB, 20 ± 5 dB, 18.3 ± 2.9 dB, and 18.3 ± 2.9 dB, respectively. At 1-day post NIHL, all groups demonstrated profound hearing loss. At 2 weeks, 2 and 10 µL Dex thresholds improved to 47.5 ± 3.5 dB and 48.8 ± 18.9 dB, respectively, whereas the untreated and saline groups remained unchanged. Mean cell counts in the cochlear nucleus (CN), superior olivary complex (SOC), and lateral lemniscus (LL) of control mice were 1483 ± 190, 2807 ± 67, and 112 ± 20, respectively. After acoustic trauma, the untreated, saline, and 2 µL Dex groups yielded decreased neuronal counts in the SOC. In contrast, the 10 µL Dex group had 1883 ± 186 (CN), 2774 ± 182 (SOC), and 166 ± 18 (LL). There was sporadic hair cell loss for all traumatized groups. Conclusion Our NIHL mouse model demonstrated dose-dependent Dex pretreatment otoprotection against NIHL with preservation of retrocochlear auditory neurons.