Apoptotic Pattern of Cochlear Outer Hair Cells and Frequency-specific Hearing Threshold Shift in Noise-exposed BALB/c Mice

Abstract

ObjectivesApoptosis of outer hair cell (OHC) can be identified through nuclear staining by specific nuclear changes. The change of filamentous actin (F-actin) is also involved in early cell death process. The study was designed to investigate OHC death along the whole length of the organ of Corti.MethodsBALB/c hybrid mice were used in this study. The noise group was exposed to white noise of 120 dB SPL for 3 hr per day for 3 consecutive days. The tone burst auditory brainstem response (ABR) test was conducted and cochleas from each group were obtained for the immunostaining of FITC phalloidin for F-actin and propidium iodide (PI) for nuclei.ResultsABR threshold of the noise group significantly increased after noise exposure (P<0.001). No threshold shift was found in the control group. Threshold shift of the noise group constantly increased from 4 to 16 kHz, but threshold shifts at 16 kHz and 32 kHz were similar. Patterns of OHC staining were subclassified as FITC+PI- cells, FITC+ PI+ cells, FITC-PI+ cells and missing cells. Proportion of normal live OHCs (FITC+PI-) rapidly decreased from the apex to the base. In the basal turn, FITC-PI+ cells and vacancy OHC (missing cells) were observed easily. Apoptotic and missing cells were most abundant at 60% of the whole length of the Corti organ.ConclusionWe could subclassify morphologic changes in OHC death after noise exposure. Quantitative changes in OHCs along the whole Corti organ showed a plateau pattern similar to that of a frequency-specific threshold shift.

Effects of Specific Cochlear Pathologies on the Auditory Functions : Modelling, Simulations and Clinical Implications

“…The OHCs are assumed to be completely dead in the most basal region (0-L/3) which corresponds to high frequencies over 6 kHz. This assumption is in line with the experimental observations which suggest that the OHCs located in most basal regions of the mammalian cochlea are significantly more vulnerable to acoustic overstimulation than the hair cells in apical areas (Fu-Guan et al, 2012;Lim et al, 2008;Pyykkö et al, 2003). Moreover, half of the OHCs located in the middle one third of the cochlear length are assumed dead.…”

“…It has been reported that a majority of destructive noises such as those in building construction environments and those produced by farming equipment lie in this frequency range (Pyykkö et al, 2003). Finally, the OHCs which are located in the most apical regions are assumed to be intact and fully active (100% integrity) in consistence with the experimental observations (Fu-Guan et al, 2012;Lim et al, 2008;Pyykkö et al, 2003).…”

“…To quantitatively study how the location, severity and length of the OHC lesions affects the Lim et al (2008) exposed a group of BALB/c hybrid mice to white noise at 122 dB SPL during 3 consecutive days, 3 hours per day and observed the morphological changes in the OHCs along the cochlear length due to the noise exposure, as well as the resulting threshold elevations. Their results showed that shortly after the noise exposures there were about 90%…”

“…The result is depicted in Fig. 5(b) of paper IV where the model prediction is shown versus the experimentally measured threshold elevations of the noise-damaged mice cochleae at 4, 8, 16 and 32 kHz (Lim et al, 2008).…”

Biophysical Mechanisms Underlying Outer Hair Cell Loss Associated with a Shortened Tectorial Membrane

“…The total length of cochlea scanned was approximately 1.4 mm. Phalloidin-negative gaps in the OHC rows were presumed to represent degenerated or missing OHCs (Lim et al 2008), and the proportion of missing OHCs was calculated for each scanned region. Cytocochleograms were created with the collected data after the percent distance from the base for each region was calculated using 5.72 mm as the average length of a CBA/CaJ mouse cochlea fixed in 4% paraformaldehyde (Viberg and Canlon 2004).…”