title: Swept-sine noise-induced damage as a hearing loss model for preclinical assays.
abstract: Mouse models are key tools for studying cochlear alterations in noise-induced hearing loss (NIHL) and for evaluating new therapies. Stimuli used to induce deafness in mice are usually white and octave band noises that include very low frequencies, considering the large mouse auditory range. We designed different sound stimuli, enriched in frequencies up to 20 kHz ("violet" noises) to examine their impact on hearing thresholds and cochlear cytoarchitecture after short exposure. In addition, we developed a cytocochleogram to quantitatively assess the ensuing structural degeneration and its functional correlation. Finally, we used this mouse model and cochleogram procedure to evaluate the potential therapeutic effect of transforming growth factor β1 (TGF-β1) inhibitors P17 and P144 on NIHL. CBA mice were exposed to violet swept-sine noise (VS) with different frequency ranges (2-20 or 9-13 kHz) and levels (105 or 120 dB SPL) for 30 min. Mice were evaluated by auditory brainstem response (ABR) and otoacoustic emission tests prior to and 2, 14 and 28 days after noise exposure. Cochlear pathology was assessed with gross histology; hair cell number was estimated by a stereological counting method. Our results indicate that functional and morphological changes induced by VS depend on the sound level and frequency composition. Partial hearing recovery followed the exposure to 105 dB SPL, whereas permanent cochlear damage resulted from the exposure to 120 dB SPL. Exposure to 9-13 kHz noise caused an auditory threshold shift (TS) in those frequencies that correlated with hair cell loss in the corresponding areas of the cochlea that were spotted on the cytocochleogram. In summary, we present mouse models of NIHL, which depending on the sound properties of the noise, cause different degrees of cochlear damage, and could therefore be used to study molecules which are potential players in hearing loss protection and repair.
authors.affiliation: Institute for Biomedical Research "Alberto Sols" (IIBM), Spanish National Research Council-Autonomous University of Madrid (CSIC-UAM) Madrid, Spain ; Centre for Biomedical Network Research (CIBER), Institute of Health Carlos III (ISCIII) Madrid, Spain ; Príncipe de Asturias University Hospital, University of Alcalá, Alcalá de Henares Madrid, Spain.
authors.forename: Lorena
authors.initials: L
authors.lastname: Sanz
authors.affiliation: Institute for Biomedical Research "Alberto Sols" (IIBM), Spanish National Research Council-Autonomous University of Madrid (CSIC-UAM) Madrid, Spain ; Centre for Biomedical Network Research (CIBER), Institute of Health Carlos III (ISCIII) Madrid, Spain ; Hospital La Paz Institute for Health Research (IdiPAZ) Madrid, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Murillo-Cuesta
authors.affiliation: Institute for Physical and Information Technologies (ITEFI), Spanish National Research Council (CSIC) Madrid, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Cobo
authors.affiliation: Institute for Biomedical Research "Alberto Sols" (IIBM), Spanish National Research Council-Autonomous University of Madrid (CSIC-UAM) Madrid, Spain ; Centre for Biomedical Network Research (CIBER), Institute of Health Carlos III (ISCIII) Madrid, Spain ; Veterinary Faculty, Complutense University of Madrid Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Cediel-Algovia
authors.affiliation: Institute for Biomedical Research "Alberto Sols" (IIBM), Spanish National Research Council-Autonomous University of Madrid (CSIC-UAM) Madrid, Spain ; Centre for Biomedical Network Research (CIBER), Institute of Health Carlos III (ISCIII) Madrid, Spain ; Veterinary Faculty, Complutense University of Madrid Madrid, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Contreras
authors.affiliation: Institute for Biomedical Research "Alberto Sols" (IIBM), Spanish National Research Council-Autonomous University of Madrid (CSIC-UAM) Madrid, Spain ; Centre for Biomedical Network Research (CIBER), Institute of Health Carlos III (ISCIII) Madrid, Spain ; Príncipe de Asturias University Hospital, University of Alcalá, Alcalá de Henares Madrid, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Rivera
authors.affiliation: Institute for Biomedical Research "Alberto Sols" (IIBM), Spanish National Research Council-Autonomous University of Madrid (CSIC-UAM) Madrid, Spain ; Centre for Biomedical Network Research (CIBER), Institute of Health Carlos III (ISCIII) Madrid, Spain ; Hospital La Paz Institute for Health Research (IdiPAZ) Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Varela-Nieto
authors.affiliation: Hospital La Paz Institute for Health Research (IdiPAZ) Madrid, Spain ; Department of Anatomy, Histology and Neuroscience, Medical School, Autónoma University of Madrid Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Avendaño
keywords: TGF-β inhibition; cytocochleogram; hair cells; hearing loss; transtympanic; violet noise