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The loss of sensory hair cells in the cochlea is the major cause of sensorineural hearing loss, and inflammatory processes and immune factors in response to cochlear damage have been shown to induce hair cell apoptosis. The expression and function of Nfatc4 in the cochlea remains unclear. In this study, we investigated the expression of Nfatc4 in the mouse cochlea and explored its function using Nfatc4 -/- mice. We first showed that Nfatc4 was expressed in the cochlear hair cells. Cochlear hair cell development and hearing function were normal in Nfatc4 -/- mice, suggesting that Nfatc4 is not critical for cochlear development. We then showed that when the hair cells were challenged by ototoxic drugs Nfatc4 was activated and translocated from the cytoplasm to the nucleus, and this was accompanied by increased expression of Tnf and its downstream targets and subsequent hair cell apoptosis. Finally, we demonstrated that Nfatc4-deficient hair cells showed lower sensitivity to damage induced by ototoxic drugs and noise exposure compared to wild type controls. The Tnf-mediated apoptosis pathway was attenuated in Nfatc4-deficient cochlear epithelium, and this might be the reason for the reduced sensitivity of Nfatc4-deficient hair cells to injury. These findings suggest that the amelioration of inflammation-mediated hair cell apoptosis by inhibition of Nfatc4 activation might have significant therapeutic value in preventing ototoxic drug or noise exposure-induced sensorineural hearing loss.

To explore the structural characteristics of the cochlea in three-dimensional (3D) detail using 3D micro-computed tomography (mCT) image reconstruction of the osseous labyrinth, with the aim of improving the structural design of electrodes, the selection of stimulation sites, and the effectiveness of cochlear implantation. Three temporal bones were selected from among adult donors' temporal bone specimens. A micro-CT apparatus (GE eXplore) was used to scan three specimens with a voxel resolution of 45 μm. We obtained about 460 slices/specimen, which produced abundant data. The osseous labyrinth images of three specimens were reconstructed from mCT. The cochlea and its spiral characteristics were measured precisely using Able Software 3D-DOCTOR. The 3D images of the osseous labyrinth, including the cochlea, vestibule, and semicircular canals, were reconstructed. The 3D models of the cochlea showed the spatial relationships and surface structural characteristics. Quantitative data concerning the cochlea and its spiral structural characteristics were analyzed with regard to cochlear implantation. The 3D reconstruction of mCT images clearly displayed the detailed spiral structural characteristics of the osseous labyrinth. Quantitative data regarding the cochlea and its spiral structural characteristics could help to improve electrode structural design, signal processing, and the effectiveness of cochlear implantation. Clin. Anat. 30:39-43, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

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Background: The transcription factor Sox2 plays important roles in the developmental processes of multiple organs and tissues. However, whether Sox2 can protect mature or terminally differentiated cells against injury is still unknown.Methods: We investigated the roles of Sox2 in cochlear hair cells, which are terminally differentiated cells, using conditional transgenic mice and several hearing loss models.Results: Sox2 overexpression dramatically mitigated the degree of cochlear hair cell loss when exposed to ototoxic drugs. Noise-induced apoptosis of cochlear hair cells and hearing loss were also significantly alleviated by Sox2 overexpression. Notably, noise-induced upregulation of pro-inflammatory factors such as TNF-α and IL6 was inhibited by Sox2 overexpression. Then we used lipopolysaccharide to clarify the effect of Sox2 on cochlear inflammation, and Sox2 overexpression significantly inhibited lipopolysaccharide-induced upregulation of pro-inflammatory factors and alleviated inflammation-related cochlear hair cell death.Conclusions: These results demonstrate a novel protective role of Sox2 in mature and terminally differentiated cochlear hair cells by inhibiting inflammation. [ABSTRACT FROM AUTHOR]