Noise damage in the C57BL/CBA mouse cochlea☆
Introduction
Over the 100+ year history of noise research, humans (e.g., Davis et al., 1950) and a number of animal species (e.g., guinea pig, chinchilla, cat, rabbit, mouse) have been used to examine the effects of noise on auditory function and structure, and to determine how noise parameters (i.e., frequency, intensity, duration and scheduling) are related to the damage potential of a particular exposure. Human studies have provided valuable information on the relation between noise exposure and the loss of auditory function (e.g., Taylor et al., 1965, Mills et al., 1970, Sulkowski, 1973, Melnick, 1976). However, research with humans has not been able to provide much information on the amount or pattern(s) of cochlear damage induced by excessive exposure to noise. This latter point is important in view of the fact that hair cell injury and loss generally precede any measurable permanent shift in pure tone thresholds (e.g., Bredberg, 1968, Clark and Bohne, 1978).
Despite the large number of histopathological studies involving the effects of noise on the cochlea, issues remain unanswered (e.g., how excessive noise first injures then destroys cells in the organ of Corti; why degeneration in the cochlea continues a long time after the exposure has terminated; why exposure at one frequency often damages two or more regions in the cochlea). These issues appear to have arisen because some researchers have attempted to elucidate general principles of noise damage but used only intense, short-duration exposures and/or evaluated only a portion of the organ of Corti.
It appears that there are several ways in which noise may damage the cochlea. Intense noises, such as explosions (i.e., >140 dB SPL), damage the cochlea instantaneously, probably by purely mechanical means. Explosions produce high-amplitude vibrations of the cochlear partition that exceed its elastic limits. The organ of Corti is torn from its attachment to the basilar membrane. With time, the bare basilar membrane is covered by undifferentiated squamous epithelium (e.g., Lurie, 1942, Hawkins et al., 1943). Explosions result in an abrupt severe hearing loss from which there is little recovery of function post-exposure (Ward and Glorig, 1961). On the other hand, noises, such as those associated with the workplace and recreational activities, probably damage the cochlea by non-mechanical mechanisms. In these instances, structural damage begins as degeneration of scattered sensory cells and continues to increase with longer or repeated exposures (e.g., Bohne, 1976, Clark and Bohne, 1978). The associated hearing loss gradually develops over time (Taylor et al., 1965).
The term ‘temporary threshold shift’ (TTS) has been used to indicate a transient impairment of auditory function due to trauma such as noise exposure. With increasing post-exposure time, a TTS completely disappears and hearing thresholds return to pre-exposure levels. The term ‘permanent threshold shift’ (PTS) has been used in instances when, post-exposure, hearing thresholds have stabilized, but are poorer than pre-exposure values. The term ‘compound threshold shift’ (CTS) was coined by Miller et al. (1963) to describe threshold shifts that have both temporary and permanent components. A CTS is at a maximum immediately post-exposure, then recovers somewhat as its temporary component resolves. It has been suggested that when a CTS is present, the TTS component masks the PTS component (e.g., Miller et al., 1963) and that the partial recovery of thresholds with increasing post-exposure time parallels the disappearance of the TTS. This suggestion implies that the structural correlates of TTS and PTS are both present immediately post-exposure. However, it was recently shown that when an animal is exposed to a moderate-level, short-duration noise, it manifests a moderate TTS immediately post-exposure and the histopathological changes are almost exclusively confined to the supporting cells. If the animal subsequently develops a PTS, the structural correlates of the PTS are not present immediately after exposure, but develop in the post-exposure period (Nordmann et al., 2000). These latter data suggest that the biochemical and cellular processes underlying TTS are distinct from those which eventually result in PTS. For this reason, the term ‘TTS’ is used here to refer to thresholds measured 0–7 days post-exposure, regardless of whether or not the animal’s thresholds eventually recovered (i.e., pure TTS) or stabilized at a reduced level (i.e., pure PTS).
It is well known that a human or animal exposed to noise of predominantly one frequency does not develop its maximum hearing loss at that frequency. Instead, the maximum threshold shift may occur one-half to two octaves above the frequency of the exposure. Humans sustain one-half to one-octave shifts after exposures to noise resulting in TTSs (Davis et al., 1950, Mills et al., 1970, Melnick, 1976). Mice have been found to sustain their maximum threshold shifts up to two octaves higher than the frequency of the exposure (Henry, 1984). The actual basis for this shift is not known, especially why the shifts range from one-half to more than two octaves, depending on species. However, it has been shown that increasing the intensity of a stimulus causes a shift in the maximum effect of the exposure toward higher frequencies (e.g., McFadden and Plattsmier, 1982). Regardless of the mechanism for the octave shift phenomenon, it is necessary to measure auditory thresholds over a range of frequencies at multiple intervals post-exposure, and to examine the organ of Corti in its entirety from apex to base to characterize fully the effects of noise on the function and structure of the cochlea.
In recent years, mice have become very desirable subjects for medical research because of the ready availability of genetically defined strains and the ability to generate knockout mice lacking specific genes. Knockout mice may be valuable for testing some of the hypothesized mechanisms of noise damage. However, in order to interpret data from knockouts and mice with other experimental perturbations, it is important to characterize the functional and structural changes in a typical mouse’s auditory system to different noises and to develop an anatomically based frequency–place map for the mouse cochlea (see companion paper).
Section snippets
Animals
The mice, purchased from The Jackson Laboratory (Bar Harbor, ME), were the first generation of a cross between homozygous C57BL mice that carry the ahl gene for age-related hearing loss and are susceptible to noise-induced hearing loss, and homozygous CBA mice that do not carry the ahl gene and are relatively resistant to age-related and noise-induced hearing loss (Erway et al., 1993). The mice were 1.75–3 months old when pre-exposure auditory brainstem response (ABR) thresholds were first
Cochlear morphometrics
Because of the paucity of data on OC parameters in the mouse cochlea, the total number of hair cells had to be counted in order to be able to calculate the percentage of missing IHCs and OHCs. Cell totals were counted in all OC segments in which hair cell losses were minimal or moderate. OC length ranged from 5.66 to 6.16 mm and averaged 5.90±0.12 mm (n=47). IHC and OHC densities per millimeter averaged, respectively, 120 and 418 in the second turn (i.e., 0–42.6% distance from apex), 128 and
ABR thresholds of C57BL/CBA F1 mice
The 44 ABR-tested mice in the present study were maximally sensitive to the 10-kHz test tone, having an average pre-exposure threshold of 45 dB SPL. Thresholds increased by 7–13 dB at lower and higher test frequencies. The shape of the curve is similar to that shown by Mikaelian et al. (1974) for behaviorally tested C57 and CBA mice, but the level is about 15 dB higher at all frequencies. This is probably due to the higher sensitivity of behavioral testing. These thresholds are also somewhat
Acknowledgements
This work was supported by the National Organization for Hearing Research, the American Heart Association, and the Department of Otolaryngology at Washington University School of Medicine. We gratefully acknowledge the technical assistance provided by Mr. Thomas J. Watkins, and the helpful input concerning experimental design and data analysis provided by the members of Dr. Ou’s thesis committee, Drs. Charles Anderson, J. Gail Neely, and Carl Rovainen. The suggestions for revision provided by
References (26)
- et al.
Processing and analyzing the mouse temporal bone to identify gross, cellular and subcellular pathology
Hear. Res.
(1997) - et al.
Genetics of age-related hearing loss in mice: I. Inbred and F1 hybrid strains
Hear. Res.
(1993) - et al.
Genetics of age-related hearing loss in mice. III. Susceptibility of inbred and F1 hybrid strains to noise-induced hearing loss
Hear. Res.
(1996) - et al.
Histopathological differences between temporary and permanent threshold shift
Hear. Res.
(2000) Safe level for noise exposure?
Ann. Otol. Rhinol. Laryngol.
(1976)- et al.
Delayed effects of ionizing radiation on the ear
Laryngoscope
(1985) - et al.
Interaural correlations in normal and traumatized cochleas: Length and sensory cell loss
J. Acoust. Soc. Am.
(1986) Cellular pattern and nerve supply of the human organ of Corti
Acta Otolaryngol. (Stockh.)
(1968)- Bohne, B.A., Harding, G.W., 2000. Degeneration in the cochlea after noise damage: Primary vs. secondary events. Am. J....
- Bredberg, G., 1973. Experimental pathology of noise-induced hearing loss. In: Hawkins, Jr., J.E., Lawrence, M., Work,...
Animal model for the 4-kHz tonal dip
Ann. Otol. Rhinol. Laryngol.
Temporary deafness following exposure to loud tones and noise
Acta Otolaryngol.
Cochlear morphology in relation to loss of behavioural, electrophysiological and middle ear reflex thresholds after exposure to noise
Acta Otolaryngol.
Cited by (69)
BDNF-enriched small extracellular vesicles protect against noise-induced hearing loss in mice
2023, Journal of Controlled ReleaseGenetics of noise-induced hearing loss in the mouse model
2022, Hearing ResearchCitation Excerpt :Further investigation into the structural etiology of delayed-onset hearing loss identified the likely culprit of acute loss of afferent nerve terminals, further exacerbated by delayed regeneration of these terminals following noise trauma, and entering cochlear synaptopathy and “hidden hearing loss” into the discussion of NIHL mechanisms (Kujawa and Liberman, 2009). Further characterization of C57BL/CBA F1 hybrids, however, has shown a very high level of variability in PTS despite supposed genetic homogeneity, underscoring multifactorial nature of hearing geneticsm and the limits of Mendelian genetics to characterize NIHL pathology (Ou et al., 2000). In the interest of broadly correlating known genomes with hearing phenotype, Johnson et al. initially described ABR phenotypes within a set of BXD strains to demonstrate that interactions between multiple distant gene loci were also associated with variations in hearing (Johnson et al., 2008).
Activation of the antigen presentation function of mononuclear phagocyte populations associated with the basilar membrane of the cochlea after acoustic overstimulation
2015, NeuroscienceCitation Excerpt :As shown in the cochleogram (Fig. 4B), the missing cells appear more frequently in the basal section of the cochlea, and the difference in the average numbers of missing cells between the apical section and the basal section is statistically significant (Fig. 4C, Student’s t test, t = −3.375, df = 13, P = 0.005). The finding of greater sensory cell damage in the basal section of the cochlea is consistent with previous reports using similar noise conditions in mice (Ou et al., 2000; Harding et al., 2005) and this pattern of damage is possibly related to weaker antioxidant capacity in the basal end of the cochlea (Sha et al., 2001). We quantified the numbers of CD45-positive cells beneath the basilar membrane and the junction of the basilar membrane and the lateral wall at three time points after exposure to the noise (1, 4, and 10 days).
Role of PGE-type receptor 4 in auditory function and noise-induced hearing loss in mice
2012, Neuropharmacology
- ☆
This work was completed as part of a thesis by H.C. Ou for the MA/MD program in Biological Sciences at Washington University School of Medicine.
- 1
Present address: Department of Otolaryngology, VMB Hearing Research Center, Box 357923, University of Washington Medical School, Seattle, WA 98195-7923, USA.