Adult mice with noise-induced hearing loss exhibited temporal ordering memory deficits accompanied by microglia-associated neuroplastic changes in the medial prefrontal cortex.

Acquired peripheral hearing loss in midlife is considered the primary modifiable risk factor for dementia, while the underlying pathological mechanism remains poorly understood. Excessive noise exposure is the most common cause of acquired peripheral hearing loss in modern society. This study was designed to investigate the impact of noise-induced hearing loss (NIHL) on cognition, with a focus on the medial prefrontal cortex (mPFC), a brain region that is involved in both auditory and cognitive processes and is highly affected in patients with cognitive impairment. Adult C57BL/6 J mice were randomly assigned to a control group and seven noise groups: 0HPN, 12HPN, 1DPN, 3DPN, 7DPN, 14DPN, and 28DPN, which were exposed to broadband noise at a 123 dB sound pressure level (SPL) for 2 h and sacrificed immediately (0 h), 12 h, or 1, 3, 7, 14, or 28 days post-noise exposure (HPN, DPN), respectively. Hearing assessment, behavioral tests, and neuromorphological studies in the mPFC were performed in control and 28DPN mice. All experimental animals were included in the time-course analysis of serum corticosterone (CORT) levels and mPFC microglial morphology. The results illustrated that noise exposure induced early-onset transient serum CORT elevation and permanent moderate-to-severe hearing loss in mice. 28DPN mice, in which permanent NIHL has been verified, exhibited impaired performance in temporal order object recognition tasks concomitant with reduced structural complexity of mPFC pyramidal neurons. The time-course immunohistochemical analysis in the mPFC revealed significantly higher morphological microglial activation at 14 and 28 DPN, preceded by a remarkably higher amount of microglial engulfed postsynaptic marker PSD95 at 7 DPN. Additionally, lipid accumulation in microglia was observed in 7DPN, 14DPN and 28DPN mice, suggesting a driving role of lipid handling deficits following excessive phagocytosis of synaptic elements in delayed and sustained microglial abnormalities. These findings provide fundamentally novel information concerning mPFC-related cognitive impairment in mice with NIHL and empirical evidence suggesting the involvement of microglial malfunction in the mPFC neurodegenerative consequences of NIHL.

Can auditory brain stem response accurately reflect the cochlear function?

Auditory brain stem response (ABR) and compound action potential (CAP) recordings have been used in animal research to determine hearing sensitivity. Because of the relative ease of testing, the ABR test has been more commonly used in assessing cochlear lesions than the CAP test. The purpose of this experiment is to examine the difference between these two methods in monitoring the dynamic changes in auditory function after cochlear damage and in detecting asymmetric hearing loss due to unilateral cochlear damage. ABR and CAP were measured in two models of cochlear damage: acoustic trauma induced by exposure to a narrowband noise centered at 4 kHz (2,800-5,600 Hz) at 105 dB sound pressure level for 5 h in chinchillas and unilateral cochlear damage induced by surgical destruction of one cochlea in guinea pigs. Cochlear hair cells were quantified after completing the evoked potential testing. In the noise-damaged model, we found different recovery patterns between ABR and CAP. At 1 day after noise exposure, the ABR and CAP assessment revealed a similar level of threshold shifts. However, at 30 days after noise exposure, ABR thresholds displayed an average of 20-dB recovery, whereas CAP thresholds showed no recovery. Notably, the CAP threshold signifies the actual condition of sensory cell pathogenesis in the cochlea because sensory cell death is known to be irreversible in mammals. After unilateral cochlear damage, we found that both CAP and ABR were affected by cross-hearing when testing the damaged ear with the testing stimuli delivered directly into the canal of the damaged ear. When cross-hearing occurred, ABR testing was not able to reveal the presence of cross-hearing because the ABR waveform generated by cross-stimulation was indistinguishable from that generated by the test ear (damaged ear), should the test ear be intact. However, CAP testing can provide a warning sign, since the typical CAP waveform became an ABR-like waveform when cross-hearing occurred. Our study demonstrates two advantages of the CAP test over the ABR test in assessing cochlear lesions: contributing evidence for the occurrence of cross-hearing when subjects have asymmetric hearing loss and providing a better assessment of the progression of cochlear pathogenesis.NEW & NOTEWORTHY Auditory brain stem response (ABR) is more commonly used to evaluate cochlear lesions than cochlear compound action potential (CAP). In a noise-induced cochlear damage model, we found that the reduced CAP and enhanced ABR caused the threshold difference. In a unilateral cochlear destruction model, a shadow curve of the ABR from the contralateral healthy ear masked the hearing loss in the destroyed ear.

The use of hyperbaric oxygen therapy in acute hearing loss: a narrative review.

INTRODUCTION: Acute hearing loss can have a major impact on a patient's life. This holds true for both acute acoustic trauma (AAT) and idiopathic sudden sensorineural hearing loss (ISSHL), two devastating conditions for which no highly effective treatment options exist. This narrative review provides the rationale and evidence for HBOT in AAT and ISSHL. METHODS: Narrative review of all the literature available on HBOT in acute hearing loss, studies were retrieved from systematic searches on PubMed and by cross referencing. DISCUSSION: First, the etiological mechanisms of acute hearing loss and the mechanism of action of HBOT were discussed. Furthermore, we have provided an overview of 68 studies that clinically investigated the effect of HBOT in the last couple of decades. For future studies, it is recommend to start as early as possible with therapy, preferably within 48 h and to use combination therapy consisting of HBOT and corticosteroids. IMPLICATIONS FOR PRACTICE: HBOT has been used quite extensively for acute hearing loss in the last couple of decades. Based on the amount of studies showing a positive effect, HBOT should be discussed with patients (shared decision making) as optional therapy in case of AAT and ISSHL.

[The diagnostics and treatment of tympanophonia]. / Diagnostika i lechenie shuma v ushakh.

Tympanophonia can be a consequence of a variety of diseases and pathological conditions diagnostics of which encounters difficulties. The comprehensive clinical examination of the patient is necessary to determine the cause of tympanophonia including elucidation of the following characteristics: initial (acute or gradual) sensation of sound in the ear(s), duration of persisting clinical manifestations, the presence of an acoustic or craniocerebral injury, characteristics of the noise, viz. continuous or intermittent, clicking sounds, paroxysmal or pulsed noise (synchronous with the heart beating), fluctuating, audible to the patient alone or to the surrounding people as well, unilateral and bilateral noises (either symmetric or asymmetric), perception of noise in the head rather than ears., high- and low-pitched noise together with the accompanying neurological symptoms. The analysis of these characteristics makes it possible to differentiate between objective and subjective sensation of noise in the ear(s), determine the amount of additional studies needed for the evaluatio of the conditions of a given patient, identify the possible cause of tympanophonia, establish the nosological diagnosis, and distinguish a group of the patients in need of emergency otological management.

[An acute acoustic injury during the early postoperative period following stapedoplasty]. / Ostraia akusticheskaia travma v rannem posleoperatsionnom periode posle stapedoplastiki.

This article was designed to report a clinical case of an acute acoustic injury inflicted by a discharge of the lightning ball during the early postoperative period in a female patient following surgical stapedoplasty. The acoustic impact resulted in a marked deterioration of hearing in the operated ear with simultaneous elevation of the threshold of bone sound conduction to above the preoperative value. It is concluded that the patients who had undergone the stapedoplastic surgical intervention should be advised to avoid strong acoustic impacts during the postoperative period.

Noise-Induced Hearing Loss: Permanent Versus Temporary Threshold Shifts and the Effects of Hair Cell Versus Neuronal Degeneration.

For decades, research on permanent noise-induced hearing loss has concentrated on the death of sensory hair cells and the associated threshold elevations. Recent work has shown that cochlear neurons are actually more vulnerable to noise, and even after exposures causing only temporary threshold elevation and no loss of hair cells, there is a rapid and irreversible loss of synaptic connections between cochlear neurons and hair cells followed by a slow degeneration of cochlear nerve cell bodies and central axons. Although this noise-induced neuropathy does not affect the audiogram, it likely reduces performance on more complex auditory tasks such as speech discrimination in noise.

Occupational noise exposure and noise-induced hearing loss are associated with work-related injuries leading to admission to hospital.

OBJECTIVE: This study focuses on work-related injuries that required admission to hospital in a population of male workers exposed to occupational noise (≥80 dBA) which some displayed a hearing loss due to their exposure. METHODS: The study population count 46 550 male workers, 1670 (3.6%) of whom incurred at least one work-related injury requiring admission to hospital within a period of 5 years following hearing tests conducted between 1987 and 2005. The noise exposure and hearing loss-related data were gathered during occupational noise-induced hearing loss (NIHL) screening. The hospital data were used to identify all members of the study population who were admitted, and the reason for admission. Finally, access to the death-related data made it possible to identify participants who died during the course of the study. Cox proportional hazards model taking into account hearing status, noise levels, age and cumulative duration of noise exposure at the time of the hearing test established the risk of work-related injuries leading to admission to hospital. RESULTS: For each dB of hearing loss, a statistically significant risk increase was observed (HR=1.01 dB 95% CI 1.006 to 1.01). An association (HR=2.36 95% CI 2.01 to 2.77) was also found between working in an occupational ambient noise ≥100 dBA and the risk of injury. CONCLUSIONS: From a safety perspective, this issue is highly relevant; especially when workers are exposed to intense ambient noise and NIHL.

Noise-induced hearing loss (NIHL) as a target of oxidative stress-mediated damage: cochlear and cortical responses after an increase in antioxidant defense.

This study addresses the relationship between cochlear oxidative damage and auditory cortical injury in a rat model of repeated noise exposure. To test the effect of increased antioxidant defenses, a water-soluble coenzyme Q10 analog (Qter) was used. We analyzed auditory function, cochlear oxidative stress, morphological alterations in auditory cortices and cochlear structures, and levels of coenzymes Q9 and Q10 (CoQ9 and CoQ10, respectively) as indicators of endogenous antioxidant capability. We report three main results. First, hearing loss and damage in hair cells and spiral ganglion was determined by noise-induced oxidative stress. Second, the acoustic trauma altered dendritic morphology and decreased spine number of II-III and V-VI layer pyramidal neurons of auditory cortices. Third, the systemic administration of the water-soluble CoQ10 analog reduced oxidative-induced cochlear damage, hearing loss, and cortical dendritic injury. Furthermore, cochlear levels of CoQ9 and CoQ10 content increased. These findings indicate that antioxidant treatment restores auditory cortical neuronal morphology and hearing function by reducing the noise-induced redox imbalance in the cochlea and the deafferentation effects upstream the acoustic pathway.

Neural changes accompanying tinnitus following unilateral acoustic trauma in the guinea pig.

Animal models of tinnitus allow us to study the relationship between changes in neural activity and the tinnitus percept. Here, guinea pigs were subjected to unilateral noise trauma and tested behaviourally for tinnitus 8 weeks later. By comparing animals with tinnitus with those without, all of which were noise-exposed, we were able to identify changes unique to the tinnitus group. Three physiological markers known to change following noise exposure were examined: spontaneous firing rates (SFRs) and burst firing in the inferior colliculus (IC), evoked auditory brainstem responses (ABRs), and the number of neurons in the cochlear nucleus containing nitric oxide synthase (NOS). We obtained behavioural evidence of tinnitus in 12 of 16 (75%) animals. Both SFRs and incidences of burst firing were elevated in the IC of all noise-exposed animals, but there were no differences between tinnitus and no-tinnitus animals. There were significant decreases in ipsilateral ABR latencies in tinnitus animals, contrary to what might be expected with a small hearing loss. Furthermore, there was an ipsilateral-contralateral asymmetry in NOS staining in the ventral cochlear nucleus (VCN) that was only apparent in tinnitus animals. Tinnitus animals had a significantly greater number of NOS-containing neurons on the noise-exposed side, whereas no-tinnitus animals did not. These data suggest that measuring NOS in the VCN and recording ABRs supplement behavioural methods for confirming tinnitus in animals, and that nitric oxide is involved in plastic neural changes associated with tinnitus.

Animal models of subjective tinnitus.

Tinnitus is one of the major audiological diseases, affecting a significant portion of the ageing society. Despite its huge personal and presumed economic impact there are only limited therapeutic options available. The reason for this deficiency lies in the very nature of the disease as it is deeply connected to elementary plasticity of auditory processing in the central nervous system. Understanding these mechanisms is essential for developing a therapy that reverses the plastic changes underlying the pathogenesis of tinnitus. This requires experiments that address individual neurons and small networks, something usually not feasible in human patients. However, in animals such invasive experiments on the level of single neurons with high spatial and temporal resolution are possible. Therefore, animal models are a very critical element in the combined efforts for engineering new therapies. This review provides an overview over the most important features of animal models of tinnitus: which laboratory species are suitable, how to induce tinnitus, and how to characterize the perceived tinnitus by behavioral means. In particular, these aspects of tinnitus animal models are discussed in the light of transferability to the human patients.

Efficacy of low-level laser therapy in the management of tinnitus due to noise-induced hearing loss: a double-blind randomized clinical trial.

Background. Several remedial modalities for the treatment of tinnitus have been proposed, but an effective standard treatment is still to be confirmed. In the present study, we aimed to evaluate the effect of low-level laser therapy on tinnitus accompanied by noise-induced hearing loss. Methods. This was a double-blind randomized clinical trial on subjects suffering from tinnitus accompanied by noise-induced hearing loss. The study intervention was 20 sessions of low-level laser therapy every other day, 20 minutes each session. Tinnitus was assessed by three methods (visual analog scale, tinnitus handicap inventory, and tinnitus loudness) at baseline, immediately and 3 months after the intervention. Results. All subjects were male workers with age range of 30-51 years. The mean tinnitus duration was 1.85 ± 0.78 years. All three measurement methods have shown improved values after laser therapy compared with the placebo both immediately and 3 months after treatment. Laser therapy revealed a U-shaped efficacy throughout the course of follow-up. Nonresponse rate of the intervention was 57% and 70% in the two assessment time points, respectively. Conclusion. This study found low-level laser therapy to be effective in alleviating tinnitus in patients with noise-induced hearing loss, although this effect has faded after 3 months of follow-up. This trial is registered with the Australian New Zealand clinical trials registry with identifier ACTRN12612000455864).

Associations Between Physiological Correlates of Cochlear Synaptopathy and Tinnitus in a Veteran Population.

PURPOSE: Animal models and human temporal bones indicate that noise exposure is a risk factor for cochlear synaptopathy, a possible etiology of tinnitus. Veterans are exposed to high levels of noise during military service. Therefore, synaptopathy may explain the high rates of noise-induced tinnitus among Veterans. Although synaptopathy cannot be directly evaluated in living humans, animal models indicate that several physiological measures are sensitive to synapse loss, including the auditory brainstem response (ABR), the middle ear muscle reflex (MEMR), and the envelope following response (EFR). The purpose of this study was to determine whether tinnitus is associated with reductions in physiological correlates of synaptopathy that parallel animal studies. METHOD: Participants with normal audiograms were grouped according to Veteran status and tinnitus report (Veterans with tinnitus, Veterans without tinnitus, and non-Veteran controls). The effects of being a Veteran with tinnitus on ABR, MEMR, and EFR measurements were independently modeled using Bayesian regression analysis. RESULTS: Modeled point estimates of MEMR and EFR magnitude showed reductions for Veterans with tinnitus compared with non-Veterans, with the most evident reduction observed for the EFR. Two different approaches were used to provide context for the Veteran tinnitus effect on the EFR by comparing to age-related reductions in EFR magnitude and synapse numbers observed in previous studies. These analyses suggested that EFR magnitude/synapse counts were reduced in Veterans with tinnitus by roughly the same amount as over 20 years of aging. CONCLUSION: These findings suggest that cochlear synaptopathy may contribute to tinnitus perception in noise-exposed Veterans. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.24347761.

Acoustic differences in tinnitus between noise-induced and non-noise-induced hearing loss.

BACKGROUND: Tinnitus, the perception of sound without external stimuli, varies across hearing loss types. The present study compared the acoustic characteristics of tinnitus in patients with noise-induced hearing loss (NIHL) and in those with hearing loss unrelated to noise exposure. OBJECTIVE: This study compared the acoustic characteristics of tinnitus in patients with noise-induced and non-noise-induced hearing loss. METHODS: A total of 403 patients with tinnitus were divided into those with noise-induced and non-noise-induced hearing loss. Patients were evaluated by pure tone audiometry (PTA), tinnitogram, transient evoked otoacoustic emission (TEOAE), distortion product otoacoustic emission (DPOAE), and auditory brainstem evoked response (ABR) tests. RESULTS: Patients with NIHL exhibited significantly higher hearing thresholds across all frequencies (125-8000 Hz) (p < .05) and reported significantly higher tinnitus intensity (p < .05). Otoacoustic emission tests showed that response rates were significantly lower (p < .05), and ABR tests found that latency periods were significantly more prolonged (p < .05), in patients with NIHL. CONCLUSIONS: Tinnitus differs acoustically between patients with NIHL and those with non-noise-induced hearing loss, with specific patterns of intensity and auditory responses. These findings emphasize the need for tailoring the management of tinnitus according to the underlying type of hearing loss.

Comparison of the risks of occupational diseases, avoidable hospitalization, and all-cause deaths between firefighters and non-firefighters: A cohort study using national health insurance claims data.

Objectives: National Health Insurance claims data were used to compare the incidence of occupational diseases, avoidable hospitalization, and all-cause death standardized incidence ratio and hazard ratio between firefighters and non-firefighters. Methods: The observation period of the study was from 2006 to 2015 and a control group (general workers and national and regional government officers/public educational officers) and a firefighter group was established. The dependent variables were occupational diseases, avoidable hospitalization (AH), and all-cause death. The analysis was conducted in three stages. First, the standardized incidence ratios were calculated using the indirect standardization method to compare the prevalence of the disease between the groups (firefighter and non-firefighter groups). Second, propensity score matching was performed for each disease in the control group. Third, the Cox proportional hazards model was applied by matching the participants. Results: The standardized incidence ratio and Cox regression analyses revealed higher rates of noise-induced hearing loss, ischemic heart disease, asthma, chronic obstructive pulmonary disease, cancer, back pain, admission due to injury, mental illness, depression, and AH for firefighters than general workers. Similarly, the rates of noise-induced hearing loss, ischemic heart disease, asthma, chronic obstructive pulmonary disease, back pain, admission due to injury, mental illness, depression, and AH were higher in the firefighter group than in the national and regional government officer/public educational officer group. Conclusions: The standardized incidence ratios and hazard ratios for most diseases were high for firefighters. Therefore, besides the prevention and management of diseases from a preventive medical perspective, management programs, including social support and social prescriptions in the health aspect, are needed.

Predicting secondary endolymphatic hydrops in patients with noise-induced hearing loss.

BACKGROUND: Long-term noise exposure may damage the cochlea and endolymph resorption system, which induces episodic vertigo and/or fluctuating hearing loss in later years. OBJECTIVE: This study adopted clinical symptoms, inner ear test battery, and/or magnetic resonance (MR) imaging to evaluate development of secondary endolymphatic hydrops (EH) in patients with noise-induced hearing loss (NIHL). METHODS: Forty NIHL patients with secondary EH were assigned to Group A. Another 40 age-and sex-matched NIHL patients without EH were assigned to Group B. All patients underwent an inner ear test battery. MR imaging was performed when diagnosis of EH was equivocal via above testing. RESULTS: Group A had significantly higher mean hearing levels (MHLs) than Group B at 1000, 2000, 4000, and 8000 Hz. Both groups displayed a significantly declining sequence of abnormality rates of the inner ear test battery. Under receiver operating characteristic (ROC) curve analysis, the cutoff threshold at 4 kHz for predicting the presence of secondary EH in NIHL patients was 52 dBHL, with a sensitivity of 62% and a specificity of 69%. CONCLUSIONS: NIHL patients revealing a typical 4 kHz dip-type audiogram with dip threshold >52 dBHL may predict development of secondary EH. A longitudinal follow-up coupled with MR imaging is required for confirmation.

A case of sudden unilateral sensorineural hearing loss with contralateral psychogenic hearing loss induced by gunshot noise.

The reasons behind sudden sensorineural hearing loss are mostly unknown, but viral infections, blood disorders, ototoxicity, noise trauma, autoimmune disease, acoustic tumor, and even mental stress may be related to the disease. In cases of hearing loss as a result of psychogenic factors, early diagnosis and adequate treatment under collaboration with the psychiatric department are crucial, since failure to take appropriate measures may result in permanent sequela. We report a case, with a review of the literature, of sudden unilateral sensorineural hearing loss with contralateral psychogenic hearing loss induced by gunshot noise.

Noise-induced tinnitus: a comparison between four clinical groups without apparent hearing loss.

The number of people with normal hearing thresholds seeking medical help for tinnitus and other hearing problems is increasing. For diagnostic purposes, existence/nonexistence of lesions or combinations of lesions in the inner ear not reflected in the audiogram was evaluated with advanced hearing tests applied to tinnitus patients with certain backgrounds, including noise exposure. For forty-six patients with pronounced tinnitus, and other symptoms, tentative diagnoses were established, including judgments of the influence of four causative factors: (1) acoustic trauma, (2) music, (3) suspected hereditary, and (4) nonauditory, for example, stress or muscular tension. They were analyzed with a test battery sensitive to lesions involving the outer hair cells, damage from impulse noise, and dysfunction of the efferent system. There were significant differences in test results between groups with individuals with the same most likely causative factor. Most patients claiming acoustic trauma had a specific type of result, 'hyper-PMTF' (psychoacoustical modulation transfer function), and abnormal test results of the efferent system. Everyone in the hereditary group had dysfunction of the efferent system. All patients working with music, except one, had some abnormality, but without specific pattern. The nonauditory group mostly had normal test results. The investigation shows that it is possible to diagnose minor cochlear lesions as well as dysfunction of the efferent system, which might be causing the tinnitus. Those abnormalities could not be detected with routine audiological tests. Malfunctioning caused by impulse noise is an obvious example of this. These findings facilitate choice of treatment, rehabilitation programs, and medicolegal decisions.

Metabolic changes in the brain and blood of rats following acoustic trauma, tinnitus and hyperacusis.

It has been increasingly recognized that tinnitus is likely to be generated by complex network changes. Acoustic trauma that causes tinnitus induces significant changes in multiple metabolic pathways in the brain. However, it is not clear whether those metabolic changes in the brain could also be reflected in blood samples and whether metabolic changes could discriminate acoustic trauma, hyperacusis and tinnitus. We analyzed brain and serum metabolic changes in rats following acoustic trauma or a sham procedure using metabolomics. Hearing levels were recorded before and after acoustic trauma and behavioral measures to quantify tinnitus and hyperacusis were conducted at 4 weeks following acoustic trauma. Tissues from 11 different brain regions and serum samples were collected at about 3 months following acoustic trauma. Among the acoustic trauma animals, eight exhibited hyperacusis-like behavior and three exhibited tinnitus-like behavior. Using Gas chromatography-mass spectrometry and multivariate statistical analysis, significant metabolic changes were found in acoustic trauma animals in both the brain and serum samples with a number of metabolic pathways significantly perturbated. Furthermore, metabolic changes in the serum were able to differentiate sham from acoustic trauma animals, as well as sham from hyperacusis animals, with high accuracy. Our results suggest that serum metabolic profiling in combination with machine learning analysis may be a promising approach for identifying biomarkers for acoustic trauma, hyperacusis and potentially, tinnitus.

Adding insult to injury: cochlear nerve degeneration after "temporary" noise-induced hearing loss.

Overexposure to intense sound can cause temporary or permanent hearing loss. Postexposure recovery of threshold sensitivity has been assumed to indicate reversal of damage to delicate mechano-sensory and neural structures of the inner ear and no persistent or delayed consequences for auditory function. Here, we show, using cochlear functional assays and confocal imaging of the inner ear in mouse, that acoustic overexposures causing moderate, but completely reversible, threshold elevation leave cochlear sensory cells intact, but cause acute loss of afferent nerve terminals and delayed degeneration of the cochlear nerve. Results suggest that noise-induced damage to the ear has progressive consequences that are considerably more widespread than are revealed by conventional threshold testing. This primary neurodegeneration should add to difficulties hearing in noisy environments, and could contribute to tinnitus, hyperacusis, and other perceptual anomalies commonly associated with inner ear damage.