Acoustic Overexposure Research Articles

Evidence for a bipolar change in distortion product otoacoustic emissions during contralateral acoustic stimulation in humans

The aim of this study was to investigate the activity of the medial olivocochlear (MOC) efferents during contralateral (CAS) and ipsilateral acoustic stimulation (IAS) by recording distortion product otoacoustic emission (DPOAE) suppression and DPOAE adaptation in humans. The main question was: do large bipolar changes in DPOAE level (transition from enhancement to suppression) also occur in humans when changing the primary tone level within a small range as described by Maison and Liberman for guinea pigs [J. Neurosci. 20, 4701-4707 (2000)]? In the present study, large bipolar changes in DPOAE level (14 dB on average across subjects) were found during CAS predominantly at frequencies where dips in the DPOAE fine structure occurred. Thus, effects of the second DPOAE source might be responsible for the observed bipolar effect. In contrast, comparable effects were not found during IAS as was reported in guinea pigs. Reproducibility of CAS DPOAEs was better than that for IAS DPOAEs. Thus, contralateral DPOAE suppression is suggested to be superior to ipsilateral DPOAE adaptation with regard to measuring the MOC reflex strength and for evaluating the vulnerability of the cochlea to acoustic overexposure in a clinical context.

Protective effect of calcineurin inhibitors on acoustic injury of the cochlea

This study examined the effect of immunosuppressants, cyclosporin A, FK506 and rapamycin on functional recovery of the cochlea after acoustic overexposure, in guinea pigs and mice. Thirty guinea pigs were exposed to a 2 kHz pure tone at 120 dB SPL for 10 min. The compound action potential threshold shift induced by acoustic overexposure was examined. Twenty-five mice were exposed to a 4 kHz pure tone at 128 dB SPL for 4 h. Auditory brainstem response was used to examine the hearing threshold shift. In both the guinea pig and mouse experiments, cyclosporin A and FK506, intraperitonally given just before acoustic overexposure, significantly decreased the hearing threshold shift one or two weeks after acoustic overexposure. However, neither rapamycin nor the FK506 and rapamycin combined treatment groups showed improvement of the threshold shift. The present findings suggest that these two calcineurin inhibitors have a protective effect against acoustic injury of the cochlea, whereas the non-calcineurin inhibitor, rapamycin, not only has no effect against acoustic injury, but rather blocked the effect of FK506. This indicated a possible role of calcineurin against acoustic injury.

Hearing impairment in TRPV4 knockout mice

Transient receptor potential channel vanilloid subfamily 4 (TRPV4), a member of TRP family, is a mechanosensitive non-selective cation channel. To investigate the role of TRPV4 in the cochlea, the hearing thresholds and effects of acoustic overexposure on the cochlea were examined in TRPV4 knockout mice. TRPV4 knockout mice at age 8 weeks exhibited normal, but those at 24 weeks revealed significantly higher thresholds by auditory brainstem response. The auditory threshold shift was significantly larger in the TRPV4 knockout than in the TRPV4+/+ mice 1 week after the acoustic overexposure of 128 dB SPL. The present findings suggest that disruption of TRPV4 causes delayed-onset hearing loss and makes the cochlea vulnerable to acoustic injury.

Dehydroepiandrosterone Sulfate Reduces Acoustic Injury of the Guinea-Pig Cochlea

The present study was performed to determine effects of dehydroepiandrosterone sulfate (DHEAS), a neurosteroid, on acoustic injury. Albino guinea pigs were exposed to a 2 kHz pure tone of 120 or 125 dB sound pressure level for 10 min immediately after intravenous administration of DHEAS. Statistically significant improvement in the compound action potential threshold shifts and in amplitude reduction of distortion-product otoacoustic emissions was observed 1 week after the acoustic overexposure in the animals treated with DHEAS. The present results suggest that DHEAS has a protective effect against acoustic injury of the cochlea.

Two types of afferent terminals innervate cochlear inner hair cells in C57BL/6J mice

Afferent synapses on inner hair cells (IHC) transfer auditory information to the central nervous system (CNS). Despite the importance of these synapses for normal hearing, their response to cochlear disease and dysfunction is not well understood. The C57BL/6J mouse is a model for presbycusis and noise-induced hearing loss because of its age-related hearing loss and susceptibility to acoustic over-exposure. In this context, we sought to establish normal synaptic structure in order to better evaluate synaptic changes due to presbycusis and noise exposure. Ultrastructural analysis of IHCs and afferent terminals was performed in a normal hearing 3-month-old C57BL/6J mouse at cochlear sites corresponding to 8, 16 and 32 kHz using semi-serial sections. A stereologic survey of random sections was conducted of IHCs in 11 additional mice. Two morphologically distinct groups of afferent terminals were identified at all 3 frequency locations in 11 out of 12 animals. “Simple” endings demonstrated classic features of bouton terminals, whereas “folded” endings were larger in size and exhibited a novel morphologic feature that consisted of a fully internalized double membrane that partially divided the terminal into two compartments. In many cases, the double membrane was continuous with the outer terminal membrane as if produced by an invagination. We still must determine the generality of these observations with respect to other mouse strains.

Heat shock transcription factor HSF1 is required for survival of sensory hair cells against acoustic overexposure

To analyze the role of heat shock response in the cochleae, we induced major heat shock proteins, Hsp70, Hsp90, and Hsp27 by perfusion of hot saline into the middle ear cavity (called ‘local heat shock’ in guinea pigs. Hsps were induced in almost all of the cochlear cells including the sensory hair cells in the organ of Corti. We showed that loss of both the sensory hair cells and the auditory function induced by acoustic overexposure was inhibited by pretreatment of the inner ear with local heat shock. To examine the role of heat shock transcription factor 1(HSF), which activates heat shock genes in response to heat shock, in the protection of sensory hair cells, we analyzed acoustic injury in HSF1-null mice. We found that the loss of sensory hair cells was more significant in HSF1-null mice compared with that of wild-type mice when mice were subjected to acoustic overexposure. These results indicate that HSF1 is required for survival of the sensory hair cells against acoustic overexposure.

Involvement of poly(ADP-ribose) synthetase in acoustic trauma of the cochlea.

We investigated effects of poly(ADP-ribose) synthetase (PARS) inhibitors on acoustic trauma. Albino guinea pigs were intravenously given 3-aminobenzamide, nicotinamide or 3-aminobenzoic acid (an inactive analog of 3-aminobenzamide) just prior to exposure to a 2 kHz pure tone of 120 dB sound pressure level (SPL) for 10 minutes. The threshold of the compound action potential (CAP) and the amplitude of distortion-product otoacoustic emissions (DPOAEs) were measured before and 4 hours after the acoustic overexposure. Statistically significant decreases in the CAP threshold shifts and significant increases in the DPOAE amplitudes were observed 4 hours after the acoustic overexposure in the animals treated with 3-aminobenzamide or nicotinamide, whereas 3-aminobenzoic acid did not exert any protective effect. These results strongly suggest that excessive activation of PARS is involved in generation of the acoustic trauma.

Restraint stress and protection from acoustic injury in mice

The phenomenon of ‘conditioning’, whereby prior exposure to moderate-level non-traumatic sound reduces the permanent injury to subsequent high-level sound exposures, is suggestive of protective effects mediated by stress-induced gene expression in other systems. To test the role of stress pathways in acoustic injury, this study investigated the effect of mild physical restraint, a classic non-acoustic elicitor of stress, on vulnerability to subsequent noise-induced hearing loss. CBA/CaJ mice were divided into groups (control, restraint-only, restraint pre-trauma, and trauma-only), and cochlear sensitivity was assessed via compound action potentials and distortion product otoacoustic emissions. Results showed that two 12-h epochs of mild physical restraint significantly reduced permanent threshold shifts from a subsequent acoustic overexposure, as long as the treatment–trauma interval was short (2 h). Concurrent measures of circulating glucocorticoids showed that the period of protection coincided with the period of elevated corticosterone. Results are consistent with the idea that cochlear protective effects may be mediated by stress pathways and that glucocorticoid levels may be an important upstream regulator of these effects.

Evaluating the protective role of the olivocochlear bundle against acoustic overexposure in rats by using Fos immunohistochemistry

Efferent inhibition on the cochlea is suggested as a possible function of the olivocochlear bundle (OCB). Substantial evidence supports the finding that the OCB may protect the inner ear from noise-induced damage. However, there is relatively less known about the effects of noise on the central auditory transmission compared to the effects on the periphery. In the present animal study, two experimental paradigms were designed to analyze the influence of OCB lesion on the central auditory transmission following acoustic overexposure. In order to evaluate the animal’s auditory function, its hearing threshold and the tone-evoked Fos expression shown in auditory nuclei were examined. Fos is a protein product of proto-oncogene c-fos. Via appropriate acoustic stimulation, Fos expression reveals the activated neuronal elements along the ascending auditory pathway. Thus, in experiment 1, no exposure sound was introduced and therefore no significant differences were shown in hearing thresholds and Fos expression among all rats, regardless of the status of their OCB. This result indicates that, without acoustic overexposure, OCB lesion caused no significant effect on brainstem auditory transmission. In contrast, in experiment 2, rats were exposed to continuous 8 kHz tones at 85 dB sound pressure level (SPL). A significantly increasing threshold was observed in rats with OCB lesion following an exposure period of 5 or 10 days. In addition, Fos expression was invisible first in rats with OCB lesion following 5-day exposure and almost no Fos expression could be examined in all rats after 10-day exposure. Taken together, the present data demonstrate that damaging the OCB renders an animal more easily vulnerable to acoustic damage than that of rat with intact OCB, and then reduces its cochlear activities, which eventually leads to increasing difficulty to induce tone-evoked Fos expression along the ascending auditory pathway.

Avian species differences in susceptibility to noise exposure

Previous studies of hair cell regeneration and hearing recovery in birds after acoustic overstimulation have involved relatively few species. Studies of the effects of acoustic overexposure typically report high variability. Though it is impossible to tell, the data so far also suggest there may be considerable species differences in the degree of damage and the time course and extent of recovery. To examine this issue, we exposed four species of birds (quail, budgerigars, canaries, and zebra finches) to identical conditions of acoustic overstimulation and systematically analyzed changes in hearing sensitivity, basilar papilla morphology, and hair cell number. Quail and budgerigars showed the greatest susceptibility to threshold shift and hair cell loss after overstimulation with either pure tone or bandpass noise, while identical types of overstimulation in canaries and zebra finches resulted in much less of a threshold shift and a smaller, more diffuse hair cell loss. All four species showed some recovery of threshold sensitivity and hair cell number over time. Canary and zebra finch hearing and hair cell number recovered to within normal limits while quail and budgerigars continued to have an approximately 20 dB threshold shift and incomplete recovery of hair cell number. In a final experiment, birds were exposed to identical wide-band noise overstimulation under conditions of artificial middle ear ventilation. Hair cell loss was substantially increased in both budgerigars and canaries suggesting that middle ear air pressure regulation and correlated changes in middle ear transfer function are one factor influencing susceptibility to acoustic overstimulation in small birds.

Efferent-mediated protection of the cochlear base from acoustic overexposure by low doses of lithium.

Many studies on anaesthetized animals and a few on awake animals have suggested that the cholinergic olivocochlear efferent feedback to outer hair cells can participate in the protection of the cochlea from acoustic overexposure. Lithium is known to stimulate acetylcholine synthesis and release in the brain and it is likely to act similarly at the level of the cochlear efferent synapses. We demonstrate here that, in the awake guinea-pig with a chronically implanted electrode on the round window of the cochlea, the temporary threshold shift induced by 1 minute exposure to different pure tones at around 90 dB sound pressure level (SPL) was reduced by as much as 40 dB, when exposure occurred after lithium treatment. The protection effect was not observed in anaesthetized animals. The effect was seen across the test frequency range of 6.4-12.5 kHz, suggesting that both 'fast' and 'slow' efferent effects are likely to be mediated by acetylcholine. Together our results provide new evidence that the olivocochlear efferents can provide a more efficient protection from acoustic overexposure when animals are awake.

Conditioning-related protection from acoustic injury: effects of chronic deefferentation and sham surgery.

The inner ear can be made less vulnerable to acoustic injury by a "conditioning" treatment involving exposure to a moderate-level acoustic stimulus before the acoustic overexposure. The present study was designed to explore the role of the olivocochlear (OC) system in this "protection." Guinea pigs were divided into a number of groups: some (trauma-only) were exposed to a traumatic noise for 4 h at 109 dB SPL; others (condition/trauma) were conditioned by daily exposure to the same noise at 85 dB SPL before the traumatic exposure. In OC-intact animals, the condition/trauma group showed significantly less permanent threshold shift (PTS) than the trauma-only group as measured via compound action potentials and distortion-product otoacoustic emissions (DPOAEs). Other animals with identical noise-exposure regimens underwent deefferentation surgery before the start of conditioning: the OC bundle (OCB) was cut in the brain stem, either at the midline (cutting the crossed OCB to both ears) or at the sulcus limitans (cutting all OC fibers to 1 side). Lesion success was quantified by measuring OC fascicles to the outer hair cell region in each ear. The results from the surgical groups showed that total loss of the OCB significantly increased the noise-induced PTS, whereas loss of the COCB only did not; that the conditioning exposure in deefferented animals increased, rather than decreased, the PTS from the traumatic exposure; and that animals undergoing sham surgery (brain stem cuts that failed to transect the OCB) appeared protected whether or not they received the conditioning noise exposure. The latter result suggests that conditioning-related protection may arise from a generalized stress response, which can be elicited by noise exposure, brain surgery, or a variety of other means. The former results make an OC role in the conditioning process, per se, difficult to assess, given the large effects of OC activity on general acoustic vulnerability.

Stability of efferent-mediated protection against acoustic overexposure with long maintenance under barbiturate anaesthesia.

When anaesthetized animals are maintained over a long period, crossed-cochlear suppressive and enhancement-in-noise effects mediated by the olivocochlear bundle (OCB), as well as some OCB neuronal responses, show time-dependent variations. The present study determined if there were any such changes in OCB-mediated crossed-cochlear protection against compound action potential (CAP) threshold losses caused by a standard loud sound exposure at 11 kHz, presented under conditions either not evoking OCB-mediated protection (i.e. monaural exposure) or evoking protection (binaural exposure). Maintaining animals for periods up to approximately 30 h from initial anaesthetization resulted in non-significant changes in pre-exposure CAP thresholds. There were also only small changes over select frequency ranges in threshold losses caused by the monaural or binaural loud sound, after a single exposure as well as when the testing of OCB function was extended to examine effects after dual successive exposures, the latter result being determined by application of a previously described additivity model. The features of OCB-mediated protection also showed good stability over the long maintenance. These results are discussed as providing further circumstantial evidence that protection is mediated by a different OCB subcomponent to that/those responsible for other OCB-mediated crossed-cochlear effects. In general, the results show that the barbiturate anaesthetic used here does not significantly modulate the crossed-cochlear OCB effect of protection, even though it has been shown elsewhere to significantly depress other crossed-cochlear OCB effects.

Chronic cochlear de-efferentation and susceptibility to permanent acoustic injury

The question of whether olivocochlear (OC) efferent feedback can decrease permanent damage from acoustic overexposure was investigated by comparing the chronic threshold shifts and cochlear histopathology in guinea pigs either surgically de-efferented or sham-operated and then exposed (awake and unrestrained) to a 109- or 112-dB narrow-band noise centered at 10 kHz for 2 h. Threshold shifts were estimated using compound action potentials; hair cell loss and stereocilia condition were evaluated via light-microscopic examination of plastic-embedded surface preparations, and the degree of de-efferentation was assessed by measuring OC fascicles in the tunnel of Corti. Among animals exposed to 109-dB noise, the mean permanent threshold shift (PTS) was less than 25 dB, and there were no significant differences between normal and de-efferented animals with respect to either physiological or histological measures of acoustic injury. Among animals exposed to 112 dB, the mean peak PTS was roughly 50 dB. There was a small (but statistically significant) increase in PTS for de-efferented animals, especially at frequencies above the region of peak threshold shift; however, the patterns of hair cell loss and stereocilia damage were statistically indistinguishable. Thus, for these particular exposure conditions, sound-evoked activity in the OC system does not play a major protective role in the auditory periphery, except perhaps for the extreme basal regions of the cochlea.

Transient-evoked otoacoustic emissions and high-frequency acoustic trauma in the guinea pig

Transient-evoked otoacoustic emissions (TEOE) disappear when hearing loss exceeds 40 dB in the range 1-4 kHz, due to impairment of cochlear outer hair cells. Early screening of sensorineural hearing losses is based on this finding. However, little is known as to the frequency specificity of TEOE abnormalities in a damaged cochlea. TEOE were recorded in 18 normally hearing guinea pigs in a range from 1.5 to 5 kHz before and after exposure to loud pure tones (3-10 kHz, 95-105 dB SPL, 1-10 min). The thresholds of eighth-nerve compound action potentials (CAP) were monitored with a round-window electrode; it was confirmed that acoustic overexposure resulted in typical high-frequency threshold elevations (10 to 50 dB). Most TEOE components were found at lower frequencies at which CAP thresholds did not change. However, a significant linear regression was found between their amplitudes and the percentage of basal cochlea with unaltered CAP thresholds (r = 0.69, p < 0.0001). Two alternative hypotheses are proposed to account for this correlation. Either acoustic trauma induced some minute cochlear damage at places tuned to low frequencies and TEOE were more sensitive to it than CAP thresholds, or significant contributions to lower-frequency TEOE came from the most damaged cochlear places tuned to much higher frequencies.

Efferent-mediated protection from acoustic overexposure: relation to slow effects of olivocochlear stimulation

1. The present study attempts to resolve discrepancies in the reported role of olivocochlear (OC) efferent activation in protecting the inner ear from acoustic overstimulation: in previous studies, activating the OC system in guinea pigs reduced the threshold shift caused by 1 min monaural exposure to a 10-kHz tone; whereas unilateral OC activation in cats had no effect on threshold shifts following binaural exposure to a 10 min 6-kHz tone. 2. In this study, anesthetized and curarized guinea pigs were exposed either monaurally or binaurally to tones of different duration (1-5 min), frequency (6 to 10 kHz) and intensity (105-118 dB SPL). For each exposure condition, threshold shifts were compared among ears with different levels of OC activation: in some cases, the OC bundle (OCB) was electrically stimulated during (and/or before) the acoustic overexposure; in others, the OCB was cut before the exposure; in control cases, the OCB was neither cut nor electrically stimulated. 3. Electrical stimulation of the OCB delivered simultaneously with acoustic overstimulation produced significant reductions in threshold shift only for acoustic exposures at higher frequencies (8 and 10 kHz) and shorter durations (1 and 2 min). The protective effects on 1-min exposures could be extinguished by prior stimulation of the OCB, i.e., if the OC stimulation was turned on 4 min before the acoustic overexposure.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of acoustic overexposure on the tonotopic organization of the nucleus magnocellularis

We assessed the effect a sound-induced cochlear lesion had on the tonotopic organization of the nucleus magnocellularis (NM) immediately after acoustic overexposure and following a twelve day recovery period. The acoustic overexposure was a 0.9 kHz tone at 120 dB sound pressure level (SPL) for 48 h. Initially after the acoustic overexposure, the tonotopic organization of the NM was statistically different from that of age-matched controls. Specifically, it appeared that the center frequencies of units in the frequency region of the NM associated with the acoustic overexposure had higher center frequencies than their control counterparts. Following a twelve day recovery period, when threshold sensitivity and frequency selectivity were operating normally, the tonotopic organization of the NM was not statistically different from age-matched controls. We suggest that the sound-induced changes in the tonotopic organization of the NM reflect peripheral damage in the basilar papilla. It has been well documented that similar exposure paradigms produce a loss of short hair cells and a degeneration of the tectorial membrane in the region of the basilar membrane associated with the overexposure. We postulate that the loss of these structures alters the micromechanics and tuning of the basilar membrane which is reflected in the observed changes in NM tonotopy. Following the recovery period, when those structures destroyed by the overexposure had regenerated and basilar membrane micromechanics were operating normally, the tonotopic organization of the NM returned to normal.

The olivocochlear bundle and protection from acoustic overexposure

Activity in the olivocochlear bundle (OCB), either sound- or shock-evoked, has been reported to decrease the temporary threshold shift (TTS) produced by acoustic overexposure. For example, in anesthetized guinea pigs, a TTS of 40 dB measured after a 1-min, monaural exposure to a high-intensity 10-kHz tone could be reduced by 20 dB when simultaneous electric stimulation was applied to the OCB [R. Rajan, J. Neurophysiol. 60, 549–568 (1988)]. Interpretation of such data was challenged by experiments in which unilaterally de-efferented cats, binaurally exposed to high-intensity 6-kHz tones for 10 min while shocking the OCB, shows no interaural differences in TTS [M. C. Liberman, J. Neurophysiol. 65, 123–132 (1991)]. More recent experiments suggest this discrepancy arose because OC-mediated effects on TTS are only present for short-duration (∼1 min) exposure to high-frequency (10 kHz and above) tones. This OC mediated ‘‘protection’’ may be related to ‘‘slow’’ suppressive effects of OCB stimulation on cochlear responses, which are also most robust for high-frequency stimulation and for OC shock trains from 1 to 2 min in duration [T. Sridhar etal., Abstracts—XVIIth ARO Midwinter Meeting (1994)]. [Work supported by NIH Grant No. DC 00188.]