Role In Noise-induced Hearing Loss Research Articles

Research progress on lipid droplet and its role in noise-induced hearing loss

Research progress on lipid droplet and its role in noise-induced hearing loss

Noise-Induced Cochlear Damage Involves PPAR Down-Regulation through the Interplay between Oxidative Stress and Inflammation.

The cross-talk between oxidative stress and inflammation seems to play a key role in noise-induced hearing loss. Several studies have addressed the role of PPAR receptors in mediating antioxidant and anti-inflammatory effects and, although its protective activity has been demonstrated in several tissues, less is known about how PPARs could be involved in cochlear dysfunction induced by noise exposure. In this study, we used an in vivo model of noise-induced hearing loss to investigate how oxidative stress and inflammation participate in cochlear dysfunction through PPAR signaling pathways. Specifically, we found a progressive decrease in PPAR expression in the cochlea after acoustic trauma, paralleled by an increase in oxidative stress and inflammation. By comparing an antioxidant (Q-ter) and an anti-inflammatory (Anakinra) treatment, we demonstrated that oxidative stress is the primary element of damage in noise-induced cochlear injury and that increased inflammation can be considered a consequence of PPAR down-regulation induced by ROS production. Indeed, by decreasing oxidative stress, PPARs returned to control values, reactivating the negative control on inflammation in a feedback loop.

Progressive Dominant Hearing Loss (Autosomal Dominant Deafness-41) and P2RX2 Gene Mutations: A Phenotype-Genotype Study.

P2RX2 encoding P2X purinoreceptor 2 has been identified as the gene responsible for autosomal dominant deafness-41 (DFNA41) as well as mediating vulnerability to noise-induced hearing loss (NIHL). The objective of this study was to investigate the audiological and molecular characteristics of P2RX2-related deafness, with emphasis on its role in NIHL by determining the audiological characteristics of a previously reported six-generation DFNA41 family with a 10-year follow-up. We have also summarized phenotype-genotype correlations of P2RX2-related deafness in human and mouse models. We describe clinical longitudinal follow-up in the DFNA41 family with P2RX2 (p.Val60Leu) mutation and perform a systematic literature search in PubMed and poster presentations on meeting/conference websites to identify current insights into P2RX2-mediated NIHL. Clinical and physical examinations of the family members were performed, and audiograms were obtained to assess the hearing thresholds. Clinical follow-up features in this DFNA41 family are presented along with correlation analyses of phenotype-genotype in all reported families with P2RX2-related deafness. Progressive hearing impairment was confirmed by history and by audiological follow-up testing in all the patients. The onset of hearing loss was between age 25 and 35 years. All affected subjects had bilateral sensorineural hearing loss involving all frequencies with some significant gender differences. Our study and the review of the literature suggest that P2RX2 plays a crucial role in predisposition to noise-induced and age-related hearing loss. A better knowledge about the P2RX2-associated genetic variants can help in developing novel therapeutic strategies. 2b Laryngoscope, 130:1657-1663, 2020.

Effect of Specific Retinoic Acid Receptor Agonists on Noise-Induced Hearing Loss.

Noise is one of the most common causes of hearing loss in industrial countries. There are many studies about chemical agents to prevent noise-induced hearing loss (NIHL). However, there is no commercially available drug yet. Retinoic acid is an active metabolite of Vitamin A; it has an anti-apoptic role in NIHL. This study aims to verify the differences among selective agonists of retinoic acid receptors (RARs) in NIHL. All-trans retinoic acid (ATRA), AM80 (selective retinoic acid receptor α agonist), AC261066 (Selective retinoic acid receptor β1 agonist), and CD1530 (Selective retinoic acid λ agonist) were injected to 6–7 weeks old CJ5BL/6 mice before noise (110 dB for 3 h) exposure. In the auditory brainstem response test pre-, post 1, 3, and 7 days after noise exposure, not only ATRA but all kinds of selective RAR agonists showed protective effects in hearing threshold and wave I amplitude. Though there was no significant difference in the level of protective effects between agonists, α agonist showed the most prominent effect in preserving hearing function as well as outer hair cells after noise exposure. In conclusion, selective agonists of RAR demonstrate comparable protective effects against NIHL to retinoic acid. Given that these selective RAR agonists have less side effects than retinoic acid, they may be promising potential drugs against NIHL.

The SIRT2 inhibitor AK-7 decreases cochlear cell apoptosis and attenuates noise-induced hearing loss

Oxidative damage plays a critical role in cochlear cell apoptosis, which is central to the physiopathology of noise-induced hearing loss (NIHL). Sirtuin 2 (SIRT2) is an NAD-dependent deacetylase that regulates cellular response to oxidative stress, however, its role in NIHL remains poorly understood. Here, we report that SIRT2 is upregulated in the cochlea after noise exposure. Functionally, the treatment of AK-7, one specific SIRT2 inhibitor, attenuates the progression of NIHL. In addition, AK-7 treatment reduces oxidative nuclear DNA damage and apoptosis in the cochlea after noise exposure. Moreover, AK-7 treatment reduces apoptosis of mouse inner ear HEI-OC1 cells exposed to oxidative stress in vitro. Taken together, these results suggest that SIRT2 inhibition with AK-7 reduces cochlear cell apoptosis through attenuating oxidative stress-induced damage, which may underlie its protective role against NIHL. This study also implies that AK-7 may have potential therapeutic significance in the intervention of NIHL.

The Antioxidant Effect of Rosmarinic Acid by Different Delivery Routes in the Animal Model of Noise-Induced Hearing Loss.

Trans-tympanic Rosmarinic Acid (RA), as compared with the systemic administration, protects against noise-induced auditory hair cell and hearing losses in rats in vivo. ROS production, lipoperoxidative damage, and an imbalance of antioxidant defences play a significant role in noise-induced hearing loss. Several molecules with antioxidant properties have been tested to restore redox homeostasis; however, drug delivery system represents a challenge for their effectiveness. In our model, acute and intense noise exposure induces hearing loss, hair cell death, and oxidative stress, with an increase in superoxide production and over-expression of lipid peroxidation in cochlear structures. RA was administrated in male Wistar rats by trans-tympanic (20 μl) and systemic (10 mg/kg) modality. In systemic administration, RA was injected 1 hour before noise exposure and once daily for the following 3 days. ABRs were measured before and at days 1, 3, 7, and 30 after noise exposure. Rhodamine-phalloidin staining, dihydroethidium and 8-isoprostane immunostainings were performed to assess and quantify outer hair cells loss, superoxide production, and lipid peroxidation in the different experimental groups. Systemic RA administration significantly decreased noise-induced hearing loss and the improvement of auditory function was paralleled by a significant reduction in cochlear oxidative stress. The trans-tympanic modality of drug administration showed a similar degree of protection both at the functional and morphological levels. The effectiveness of RA given via trans-tympanic injection could be interesting for the future application of this minimally-invasive procedure in the treatment of ROS-induced hearing loss.

Association between histone deacetylases and the loss of cochlear hair cells: Role of the former in noise-induced hearing loss.

Noise-induced hearing loss (NIHL) is one of the most frequent disabilities in industrialized countries. It has been demonstrated that hair cell loss in the auditory end organ may account for the majority of ear pathological conditions. Previous studies have indicated that histone deacetylases (HDACs) play an important role in neurodegenerative diseases, including hearing impairment, in older persons. Thus, we hypothesized that the inhibition of HDACs would prevent hair cell loss and, consequently, NIHL. In the present study, a CBA/J mouse model of NIHL was established. Following an injection with the HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA), the expression levels of HDAC1, HDAC4 and acetyl-histone H3 (Lys9) (H3-AcK9) were measured. The number of hair cells was quantified and their morphology was observed. The results revealed that 1 h following exposure to 110 dB SPL broadband noise, there was a significant increase in HDAC1 and HDAC4 expression, and a marked decrease in the H3-AcK9 protein levels, as shown by western blot analysis. Pre-treatment with SAHA significantly inhibited these effects. Two weeks following exposure to noise, the mice exhibited significant hearing impairment and an obvious loss in the number of outer hair cells. An abnormal cell morphology with cilia damage was also observed. Pre-treatment with SAHA markedly attenuated these noise-induced effects. Taken together, the findings of our study suggest that HDAC expression is associated with outer hair cell function and plays a significant role in NIHL. Our data indicate that SAHA may be a potential therapeutic agent for the prevention of NIHL.

Inhaled hydrogen gas therapy for prevention of noise-induced hearing loss through reducing reactive oxygen species

Reactive oxygen species (ROS) that form in the inner ear play an important role in noise-induced hearing loss (NIHL). Recent studies have revealed that molecular hydrogen (H2) has great potential for reducing ROS. In this study, we examined the potential of hydrogen gas to protect against NIHL. We tested this hypothesis in guinea pigs with 0.5%, 1.0% and 1.5% H2 inhalation in air for 5h a day after noise exposure, for five consecutive days. All animals underwent measurements for auditory brainstem response after the noise exposure; the results revealed that there was a better improvement in the threshold shift for the 1.0% and 1.5% H2-treated groups than the non-treated group. Furthermore, outer hair cell (OHC) loss was examined 7 days after noise exposure. A significantly higher survival rate of OHCs was observed in the 1.0% and 1.5% H2-treated group as compared to that of the non-treated group in the basal turn. Immunohistochemical analyses for 8-hydroxy-2′-deoxyguanosine (8-OHdG) were performed to examine the amount of oxidative DNA damage. While strong immunoreactivities against 8-OHdG were observed of the non-treated group, the H2-treated group showed decreased immunoreactivity for 8-OHdG. These findings strongly suggest that inhaled hydrogen gas protects against NIHL.

Protective Effect of Silymarin on Noise-Induced Hearing Loss in Guinea Pigs

BackgroundHearing capability plays a principal role on human's communication. Noise-induced hearing loss (NIHL) caused by exposure to high noise levels is a serious socio-economic problem in modern societies. NIHL can either be reversible, resulting in a temporary threshold shifts (TTS) or irreversible, resulting in a permanent threshold shifts (PTS). PTS is often confirmed in the time span of between 2 - 6 weeks. NIHL may be prevented by avoidance of excessive amounts of noise or reducing the sound energy entering the inner ear using hearing protective devices. However, there are some conditions that such prevention is not possible such as noise exceeding the protective capabilities of the hearing protection device, working in military or the person does not tolerate the protection device. Thus the protective agent for preventing NIHL would be useful.ObjectiveFree radical molecules and consequence oxidative stress have been shown to play a significant role in noise-induced hearing loss. Silymarin is an antioxidant flavonoid complex derived from the herb milk thistle has ability to mitigating the oxidative stress, scavenge free radicals. In the current study, we aimed to evaluate the protective effect of silymarin on noise induced hearing loss in guinea pig by auditory brain stem response.Materials and MethodsTwenty guinea pigs randomly divided into 2 groups. The animals in the experimental group were intraperitoneally injected with 100 mg/kg/day silymarin dissolved in propylene glycol for 6 consecutive days. The control subjects were intraperitoneally injected with propylene glycol for 6 consecutive days. All animals were exposed to 4 kHz octave band noise at 120 dB SPL for 6 hours. Auditory brainstem responses (ABRs) at frequencies of 2, 4, 6, 8, 12, 16 and 20 kHz were precisely recorded before intervention and then on intervals of 0, 3, 10 and 15 days after noise exposure. Data were analyzed using repeated measures ANOVA.ResultsThreshold shifts for the experimental group at all frequencies immediately, 3, 10 and 15 days after noise exposure were significantly reduced compared to the control group (P < 0.01).ConclusionsThe findings indicate a protective effect of silymarin on temporary and permanent noise-induced hearing loss.

Interaction of a calcium channel blocker with noise in cochlear function in guinea pig

Conclusions: Both nifedipine and noise exposure had damaging effects on cochlear function. These damaging effects were subtractive rather than additive, suggesting that calcium channel blockers may have a protective role in noise-induced hearing loss. Objective: We assessed the interaction of nifedipine, a calcium channel blocker, with noise in cochlear function by evaluating changes in the compound action potential (CAP) threshold after the administration of nifedipine with or without noise exposure. Methods: Eighty guinea pigs were randomly assigned to eight groups based on those with cochlear perfusion with nifedipine only (0, 0.15, 0.5, and 3 µM, groups 1–4) and noise exposure (groups 5–8). CAP thresholds were recorded using a round window electrode before and 120 min after cochlear perfusion. Results: Cochlear perfusion of different concentrations of nifedipine caused 2.5, 5.5, 28, and 21.5 dB SPL threshold shift, respectively, at 0, 0.15, 0.5, and 3 µM concentrations (groups 1–4). In comparison, the CAP thresholds after nifedipine perfusion with noise exposure were 43.5, 46.5, 20, and 21.5 dB SPL, respectively, in groups 5–8.

Protective Role of Hydrogen Sulfide against Noise-Induced Cochlear Damage: A Chronic Intracochlear Infusion Model

BackgroundA reduction in cochlear blood flow plays an essential role in noise-induced hearing loss (NIHL). The timely regulation of cochlear perfusion determines the progression and prognosis of NIHL. Hydrogen sulfide (H2S) has attracted increasing interest as a vasodilator in cardiovascular systems. This study identified the role of H2S in cochlear blood flow regulation and noise protection.Methodology/Principal FindingsThe gene and protein expression of the H2S synthetase cystathionine-γ-lyase (CSE) in the rat cochlea was examined using immunofluorescence and real-time PCR. Cochlear CSE mRNA levels varied according to the duration of noise exposure. A chronic intracochlear infusion model was built and artificial perilymph (AP), NaHS or DL-propargylglycine (PPG) were locally administered. Local sodium hydrosulfide (NaHS) significantly increased cochlear perfusion post-noise exposure. Cochlear morphological damage and hearing loss were alleviated in the NaHS group as measured by conventional auditory brainstem response (ABR), cochlear scanning electron microscope (SEM) and outer hair cell (OHC) count. The highest percentage of OHC loss occurred in the PPG group.Conclusions/SignificanceOur results suggest that H2S plays an important role in the regulation of cochlear blood flow and the protection against noise. Further studies may identify a new preventive and therapeutic perspective on NIHL and other blood supply-related inner ear diseases.

Protective properties of antioxidant drugs in noise-induced hearing loss in the guinea pig

Oxidative stress plays a significant role in noise-induced hearing loss (NIHL), as it largely participates in the mechanisms that underlie cell death after noise exposure and lead to sensorineural hearing loss. Many antioxidant drugs have been tested to prevent NIHL. We present three molecules with antioxidant properties (vitamin E, idebenone, N-L-acetylcysteine) that have been studied in our laboratory, and compare their protective effects. We induced acoustic trauma in treated guinea pigs, evaluated their hearing function via electrophysiological measurements at 1, 7 and 21 days, and performed morphological studies with scanning electron microscopy and TUNEL assay. All molecules had a certain effect in protecting hair cells from oxidative stress; vitamin E offered almost complete protection (80–95%), N-L-acetylcysteine and idebenone also significantly reduced the threshold shift and hair cell loss. Our results support the effectiveness of antioxidant drugs in protecting against NIHL and provide a ration...

Noise-induced time-dependent changes in oxidative stress in the mouse cochlea and attenuation by d-methionine

Oxidative stress in the cochlea is considered to play an important role in noise-induced hearing loss. This study determined changes in superoxide dismutase (SOD), catalase, lipid peroxidation (LPO) and the auditory brainstem response (ABR) in the cochlea of C57BL/6 mice prior to and immediately, 1, 3, 7, 10, 14 and 21 days after noise exposure (4 kHz octave band at the intensity of 110 dB SPL for 4 h). A significant increase in SOD activity immediately and on 1st day after noise exposure, without a concomitant increase in catalase activity suggested a difference in the time dependent changes in the scavenging enzymes, which facilitates the increase in LPO observed on day 7. The ABR indicated significant noise-induced functional deficits which stabilized in 2 weeks with a permanent threshold shift (PTS) of 15 dB at both 4 kHz and 8 kHz. The antioxidant d-methionine ( d-Met) reversed the noise-induced changes in LPO levels and enzyme activities. It also significantly reduced the PTS observed on the 14th day from 15 dB to 5 dB for 4 kHz. In summary, the findings indicate that time-dependent alterations in scavenging enzymes facilitate the production of reactive oxygen species and that d-met effectively attenuates noise-induced oxidative stress and the associated functional loss in the mouse cochlea.

Prevention of impulse noise-induced hearing loss with antioxidants

ConclusionThese findings indicate a strong protective effect of ALCAR and NAC on impulse noise-induced cochlear damage, and suggest the feasibility of using clinically available antioxidant compounds to protect the ear from acute acoustic injury.ObjectiveReactive oxygen species have been shown to play a significant role in noise-induced hearing loss. In the current study, the protective effects of two antioxidants, acetyl-L-carnitine (ALCAR) and N-L-acetylcysteine (NAC), were investigated in a chinchilla model of hearing loss resulting from impulse noise. It was hypothesized that pre- and post-treatment with these antioxidants would ameliorate the effects of impulse noise compared to saline-treated controls.Material and methodsEighteen animals were randomly assigned to 1 of 3 groups and exposed to impulse noise at a level of 155 dB peak SPL for 150 repetitions. ALCAR or NAC were administered twice daily (b.i.d.) for 2 days and 1 h prior to and 1 h following noise exposure, and then b.i.d. for the following 2 days. For the control group, saline was injected at the same time points. Auditory brainstem responses (ABRs) were recorded. Cochlear surface preparations were made to obtain cytocochleograms.ResultsThree weeks after exposure, permanent threshold shifts for the experimental groups were significantly reduced to ≈10–30 dB less than that for the control group (p<0.01). Less hair cell loss was also observed in the ALCAR and NAC groups than in the control group.

Delayed production of free radicals following noise exposure

Reactive oxygen and reactive nitrogen species (ROS, RNS) formed in the inner ear in response to high-intensity noise are thought to play an important role in noise-induced hearing loss (NIHL). ROS appear rapidly and transiently in the inner ear during and following noise exposure, while hair cell loss progresses over time stabilizing two or more weeks after insult. Although the delayed loss may, in part, reflect slowly progressing apoptotic or necrosis pathways, an alternate hypothesis is that a continued formation of free radicals contributes to cell death. To evaluate this hypothesis, we measured auditory brain stem responses (ABRs), hair cell loss, and free radical activity in the guinea pig following noise exposure (5 h, 120 dB SPL, 1 OCB). Nitrotyrosine (NT) and 4-hydroxy-2-noneal (4-HNE) were used as histochemical markers of RNS and ROS formation, respectively. Assessments were performed prior to and on Days 1, 3, 7, 10, 14 and 21 after exposure. Immunoreactivity to NT and 4-HNE was low initially, reached a maximum at 7 to 10 days, and then declined. ABR thresholds increased maximally immediately after exposure, with partial recovery stabilizing at 7 to 10 days. Correlating with the delayed formation of ROS/RNS, there was a progressive hair cell loss, stabilizing at approximately 2 weeks. Based on these findings, we suggest that initial hair cell damage after noise may primarily reflect mechanical events plus transient intense ROS formation, while continued formation of ROS/RNS contributes to the long-term hair cell loss. The late formation of free radicals may provide a window of opportunity for pharmacological rescue immediately following exposure, requiring both ROS and RNS scavengers.

NMDA receptor blockage protects against permanent noise-induced hearing loss but not its potentiation by carbon monoxide

While a clear role has been proposed for glutamate as a putative neurotransmitter at the inner hair cell type I spiral ganglion cell synapse, the possible role of excessive glutamate release in cochlear impairment and of NMDA receptors in such a process is uncertain. The present study compares the protective effects of (+)-MK-801, an NMDA receptor antagonist, and the relatively inactive isomer (−)-MK-801 against permanent noise-induced hearing loss (NIHL). The study also asks whether (+)-MK-801 can protect against the NIHL potentiation by carbon monoxide (CO). Rats ( n=6) were exposed to 100-dB, 13.6-kHz octave-band noise for 2 h after receiving injection of (+)-MK-801 hydrogen maleate (1 mg/kg), (−)-MK-801 hydrogen maleate (1 mg/kg), or saline. Other groups of animals were exposed to the combination of noise and CO (1200 ppm) after receiving (+)-MK-801 or saline. Additional subjects received (+)-MK-801, saline or CO exposure alone. Compound action potential (CAP) threshold sensitivities were compared 4 weeks after the exposures. The results show significant protection by (+)-MK-801 against the permanent CAP threshold elevation induced by noise alone, but no protective effect of (−)-MK-801. (+)-MK-801 produced limited protection against threshold shifts induced by the combination of noise and CO. Outer hair cell (OHC) loss was not protected by (+)-MK-801 administration. The data suggest that NMDA receptor stimulation may play a role in NIHL resulting from fairly mild noise exposure. The data do not support a role for NMDA receptor stimulation in the potentiation of NIHL that results from simultaneous exposure to CO and noise.

Glutathione limits noise-induced hearing loss

The generation of reactive oxygen species (ROS) is thought to be part of the mechanism underlying noise-induced hearing loss (NIHL). Glutathione (GSH) is an important cellular antioxidant that limits cell damage by ROS. In this study, we investigated the effectiveness of a GSH supplement to protect GSH-deficient animals from NIHL. Pigmented guinea pigs were exposed to a 4 kHz octave band noise, 115 dB SPL, for 5 h. Group 1 had a normal diet, while groups 2, 3 and 4 were fed a 7% low protein diet (leading to lowered tissue levels of GSH) for 10 days prior to noise exposure. One hour before, immediately after and 5 h after noise exposure, subjects received either an intraperitoneal injection of 5 ml/kg body weight of 0.9% NaCl (groups 1 and 2), 0.4 M glutathione monoethyl ester (GSHE; group 3) or 0.8 M GSHE (group 4). Auditory thresholds were measured by evoked brain stem response at 2, 4, 8, 12, 16 and 20 kHz before and after noise exposure. Ten days post exposure, group 1 showed noise-induced threshold shifts of approximately 20 dB at 2, 16 and 20 kHz and 35 to 40 dB at other frequencies. Threshold shifts in group 2 were significantly greater than baseline at 2, 4, 16 and 20 kHz. GSHE supplementation in a dose-dependent fashion attenuated the threshold shifts in the low protein diet animals. Hair cell loss, as evaluated with cytocochleograms, was consistent with the auditory-evoked brainstem response results. Group 2 exhibited significantly more hair cell loss than any of the other groups; hair cell loss in group 3 was similar to that seen in group 1; group 4 showed less loss than group 1. These results indicate that GSH is a significant factor in limiting noise-induced cochlear damage. This is compatible with the notion that ROS generation plays a role in NIHL and that antioxidant treatment may be an effective prophylactic intervention.

Attenuation of cochlear damage from noise trauma by an iron chelator, a free radical scavenger and glial cell line-derived neurotrophic factor in vivo

Tissue injury by reactive oxygen species (ROS) may play a role in noise-induced hearing loss (NIHL). Since iron is involved in ROS generation, we studied if an iron chelator, deferoxamine mesylate (DFO), alone or in combination with mannitol, a hydroxyl scavenger and weak iron chelator, attenuates NIHL. Further, we investigated if glial cell line-derived neurotrophic factor (GDNF) provides additive or synergistic protection of the cochlea from acoustic trauma when given together with DFO and mannitol. Pigmented female guinea pigs were exposed to noise (4 kHz octave band, 115 dB SPL, 5 h). One hour before, immediately after, and 5 h after noise exposure, subjects received an injection of 5 ml saline/kg (control, group I), 100 mg DFO/kg (group II), 15 mg mannitol/kg (group III), or both DFO and mannitol (group IV and V). Animals in group V underwent implantation of an osmotic pump filled with GDNF (100 ng/ml) in the left ear 4 days before noise. Each treatment afforded some protection from noise damage. Group I showed significantly greater outer hair cell loss and threshold shifts at two or more frequencies compared to groups II through V. GDNF provided an additive functional, but not morphological, protection with DFO and mannitol. These findings indicate that iron chelators can attenuate NIHL, as do ROS scavengers, supporting the notion that ROS generation plays a role in NIHL. Additional functional protection provided with GDNF suggests that GDNF may attenuate noise-induced cochlear damage through a mechanism that is additive with antioxidants.

Effect of Acoustic Trauma on Cytochrome Oxidase Activity in Stria vascularis

The present study was undertaken to determine the role of metabolic disturbance in noise-induced hearing loss by histochemical studies of cytochrome oxidase activity. Adult normal albino guinea pigs were used. The experimental animals were exposed to broad-band noise at 105 dB SPL for 24 h. The control animals were not exposed to the noise. The thresholds of the auditory brainstem response (ABR) of all guinea pigs were measured 3 times: before noise exposure, 1 day and 1 month later. The difference between the ABR thresholds before and after noise exposure was statistically significant. Vibratome sections of decalcified cochleae of the noise-exposed (n = 8) and control groups (n = 4) were incubated with Spector’s medium and embedded with Epon. Thin sections (2 µm) and ultrathin sections (100 nm) were cut to observe cytochrome oxidase activity in the stria vascularis under light and electron microscopes, respectively. A decreased activity of cytochrome oxidase was consistently shown in the normal-appearing stria vascularis of most noise-exposed ears. Acoustic trauma has an adverse effect on cytochrome oxidase activity in the stria vascularis as well as on hearing. A decrease in the activity of cytochrome oxidase implicates that metabolic damage may play a role in noise-induced hearing loss.

Carbon monoxide exposure potentiates high-frequency auditory threshold shifts induced by noise.

Hypoxia has long been hypothesized to play a role in noise-induced hearing loss, and the disruption of auditory function by asphyxiation has been repeatedly demonstrated. Recent data, however, suggest that the cochlea is resistant to less extreme hypoxic events. The current report describes the combined effects of noise and hypoxia on a measure of auditory function, in an effort to clarify the role of hypoxia in hearing loss. Exposure to 1200 parts per million of carbon monoxide in air for 90 min preceding and 120 min concurrent with exposure to a broad-band noise at 110 dBA produced high-frequency threshold shifts of greater magnitude than those produced by exposure to noise alone. An equivalent carbon monoxide exposure in a 'quiet' environment did not produce any change in auditory detection thresholds. The potentiation of noise-induced threshold shifts by carbon monoxide provides additional support for the hypothesized role of metabolic exhaustion or bloodflow impairment in noise-induced hearing loss. It also suggests a possible interpretation of clinical findings of auditory impairment associated with carbon monoxide exposure.