Search Results (37)

A single intratympanic application of the small-molecule drug AC102 was previously shown to promote significant recovery of hearing thresholds in a noise-induced hearing loss model in guinea pigs. Here, we report the effects of AC102 to revert synaptopathy of inner hair cells (IHCs) and behavioral signs of tinnitus in Mongolian gerbils following mild noise trauma. This experimental protocol led to minor hearing threshold shifts with no loss of auditory hair cells (HCs) but induced synaptopathy and a sustained and significant tinnitus percept. Treatment by intratympanic application of AC102 was evaluated in two protocols: 1. three weekly injections or 2. a single application. We evaluated hearing threshold changes using the auditory brainstem response (ABR) and the development of a tinnitus percept using the gap prepulse inhibition of acoustic startle (GPIAS) behavioral response. The number of IHC ribbon synapses along the cochlear frequency map were counted by immunostaining for the synaptic ribbon protein carboxy-terminal binding protein 2 (CTBP2). AC102 strongly and significantly reduced behavioral signs of tinnitus, as reflected by altered GPIAS. Noise-induced loss of IHC ribbon synapses was significantly reduced by AC102 compared to vehicle-treated ears. These results demonstrate that a single application of AC102 restores ribbon synapses following mild noise trauma thereby promoting recovery from tinnitus-related behavioral responses in vivo. Full article

Firefighters experience high noise levels from various sources, such as sirens, alarms, pumps, and emergency vehicles. Unlike industrial workers who experience continuous noise exposure, firefighters are subject to intermittent high-intensity noise, increasing their risk of noise-induced hearing loss (NIHL). Despite global concerns regarding firefighters’ auditory health, research on Korean firefighters remains limited. This study aimed to assess personal noise exposure among Korean firefighters across three primary job roles—fire suppression, rescue, and emergency medical services (EMS)—and to predict worst-case noise exposure scenarios. This study included 115 firefighters from three fire stations (one urban, two suburban). We measured personal noise exposure using dosimeters attached near the ear following the Korean Ministry of Employment and Labor (MOEL) and International Organization for Standardization (ISO) criteria. Measurements included threshold levels of 80 dBA, exchange rates of 5 dB (MOEL) and 3 dB (ISO), and a peak noise criterion of 140 dBC. We categorized firefighters’ activities into routine tasks (shift handovers, equipment checks, training) and emergency responses (fire suppression, rescues, EMS calls). We performed statistical analyses to compare noise levels across job roles, vehicle types, and specific tasks. The worst-case exposure scenarios were estimated using 10th percentile recorded noise levels. The average 8 h time-weighted noise exposure levels varied significantly by job role. Rescue personnel exhibited the highest mean noise exposure (MOEL: 71.4 dBA, ISO: 81.2 dBA; p < 0.05), whereas fire suppression (MOEL: 66.5 dBA, ISO: 74.2 dBA) and EMS personnel (MOEL: 68.6 dBA, ISO: 73.0 dBA) showed no significant difference. Peak noise levels exceeding 140 dBC were most frequently observed in rescue operations (33.3%), followed by fire suppression (30.2%) and EMS (27.2%). Among vehicles, noise exposure was the highest for rescue truck occupants. Additionally, EMS personnel inside ambulances had significantly higher noise levels than drivers (p < 0.05). Certain tasks, including shift handovers, equipment checks, and firefighter training, recorded noise levels exceeding 100 dBA. Worst-case scenario predictions indicated that some work conditions could lead to 8 h average exposures surpassing MOEL (91.4 dBA) and ISO (98.7 dBA) limits. In this study, Korean firefighters exhibited relatively low average noise levels. However, when analyzing specific tasks, exposure was sufficiently high enough to cause hearing loss. Despite NIHL risks, firefighters rarely used hearing protection, particularly during routine tasks. This emphasizes the urgent need for hearing conservation programs, including mandatory hearing protection during high-noise activities, noise exposure education, and the adoption of communication-friendly protective devices. Future research should explore long-term auditory health outcomes and assess the effectiveness of noise control measures. Full article

Noise-induced hearing loss (NIHL) is a common type of sensorineural hearing loss caused by exposure to high-intensity noise that leads to irreversible cochlear damage. Despite extensive research on cochlear pathophysiology, the precise mechanisms remain unclear, and no established treatment exists. This is due to the challenges in imaging and the inability to perform biopsies in human patients. Consequently, animal models, particularly mice, have been widely used to study NIHL. Clinically, NIHL presents as either a temporary threshold shift, in which hearing recovers, or a permanent threshold shift, which results in an irreversible loss. Histopathological studies have identified the key features of NIHL, including outer hair cell loss, auditory nerve degeneration, and synaptic impairment. Recent findings suggest that oxidative stress and inflammation are major contributors to NIHL, highlighting the potential for therapeutic interventions, such as antioxidants and anti-inflammatory agents. Given the increasing prevalence of NIHL owing to occupational noise exposure and personal audio device use, addressing this issue is a pressing public health challenge. This review summarizes the clinical features, underlying mechanisms, and emerging treatment strategies for NIHL while identifying current knowledge gaps and future research directions. Full article

Background: Preserving residual hearing after cochlear implant (CI) surgery remains a crucial challenge. The application of dexamethasone (DEX) has been proven to positively affect residual hearing. To deliver DEX in a localized and controlled way, a round window niche implant (RNI), allowing drug diffusion via the round window membrane into the cochlea, may be used. To prove this concept, an RNI for guinea pigs as a CI-trauma model was manufactured by molding and tested for its drug release in vitro and biological effects in vivo. Methods: The RNIs were molded using silicone containing 10% DEX. Release was analyzed over time using high-performance liquid chromatography (HPLC). Fourteen adult guinea pigs were randomly assigned to two groups (CI or CI + RNI group). All animals received a unilateral CI electrode insertion trauma followed by CI insertion. The CI + RNI group was additionally implanted with an RNI containing 10% DEX. Animals were followed up for 4 weeks. Acoustically evoked auditory brainstem response and impedance measurement, micro-computed tomography (µCT) imaging, and histology were performed for evaluation. Results: DEX was released for more than 250 days in vitro, with an initial burst followed by a slower release over time. Comparing the hearing threshold shift (from day 0 to day 28) of the CI and CI + RNI groups, significant differences were observed at 32 and 40 kHz. The impedance shift at basal contacts was lower in the CI + RNI group than in the CI group. Moreover, the fibrosis in the lower basal turn was reduced in the CI + RNI group in contrast to the CI group. Conclusions: The RNI containing 10% DEX has anti-inflammatory potential concerning fibrosis inhibition and has beneficial effects on hearing preservation at high frequencies. Full article

Cisplatin is an election chemotherapeutic agent used for many cancer treatments. Its cytotoxicity against neoplastic cells is mirrored by that taking place in healthy cells and tissues, resulting in serious adverse events. A very frequent one is ototoxicity, causing hearing loss which may permanently affect quality of life after successful oncologic treatments. Exacerbated oxidative stress is a main cytotoxic mechanism of cisplatin, including ototoxicity. Previous reports have shown antioxidant protection against cisplatin ototoxicity, but there is a lack of comparative studies on the otoprotectant activity and mechanism of antioxidant formulations. Here, we show evidence that a cocktail of vitamins A, C, and E along with Mg⁺⁺ (ACEMg), previously shown to protect against noise-induced hearing loss, reverses auditory threshold shifts, promotes outer hair cell survival, and attenuates oxidative stress in the cochlea after cisplatin treatment, thus protecting against extreme cisplatin ototoxicity in rats. The addition of 500 mg N-acetylcysteine (NAC), which, administered individually, also shows significant attenuation of cisplatin ototoxicity, to the ACEMg formulation results in functional degradation of ACEMg otoprotection. Mg⁺⁺ administered alone, as MgSO₄, also prevents cisplatin ototoxicity, but in combination with 500 mg NAC, otoprotection is also greatly degraded. Increasing the dose of NAC to 1000 mg also results in dramatic loss of otoprotection activity compared with 500 mg NAC. These findings support that single antioxidants or antioxidant combinations, particularly ACEMg in this experimental series, have significant otoprotection efficacy against cisplatin ototoxicity. However, an excess of combined antioxidants and/or elevated doses, above a yet-to-be-defined “antioxidation threshold”, results in unrecoverable redox imbalance with loss of otoprotectant activity. Full article

Age-related hearing loss (ARHL) impairs the quality of life in elderly persons. ARHL is associated with comorbidities, such as depression, falls, or frailty. Frailty syndrome is related to poor health outcomes in old age. ARHL is a potentially modifiable risk factor for frailty. Oxidative stress has been proposed as a key factor underlying the onset and/or development of ARHL and frailty. Cocoa has high levels of polyphenols and provides many health benefits due to its antioxidant properties. Male and female C57Bl/6J mice were randomly assigned to two study groups: animals receiving a cocoa-supplemented diet and the other receiving a standard diet. Then, at the ages of 6, 14, and 22 months, hearing and frailty were measured in all mice. Auditory steady-state responses (ASSR) threshold shifts were measured to different frequencies. The frailty score was based on the “Valencia Score” adapted to the experimental animals. The total antioxidant capacity and total polyphenols in urine samples were also measured. Significant improvements in hearing ability are observed in the cocoa groups at 6, 14, and 22 months compared to the no cocoa group. The cocoa diet significantly retards the development of frailty in mice. Cocoa increases the concentration of polyphenols excreted in the urine, which increases the total antioxidant capacity. In conclusion, cocoa, due to its antioxidant properties, leads to significant protection against ARHL and frailty. Full article

Background and Objectives: Epidemiological data indicate that blast exposure is the most common morbidity responsible for mild TBI among Service Members (SMs) during recent military operations. Blast-induced tinnitus is a comorbidity frequently reported by veterans, and despite its wide prevalence, it is also one of the least understood. Tinnitus arising from blast exposure is usually associated with direct structural damage that results in a conductive and sensorineural impairment in the auditory system. Tinnitus is also believed to be initiated by abnormal neuronal activities and temporal changes in neuroplasticity. Clinically, it is observed that tinnitus is frequently accompanied by sleep disruption as well as increased anxiety. In this study, we elucidated some of the mechanistic aspects of sensorineural injury caused by exposure to both shock waves and impulsive noise. The isolated conductive auditory damage hypothesis was minimized by employing an animal model wherein both ears were protected. Materials and Methods: After the exposure, the animals’ hearing circuitry status was evaluated via acoustic startle response (ASR) to distinguish between hearing loss and tinnitus. We also compared the blast-induced tinnitus against the well-established sodium salicylate-induced tinnitus model as the positive control. The state of the sensorineural auditory system was evaluated by auditory brainstem response (ABR), and this test helped examine the neuronal circuits between the cochlea and inferior colliculus. We then further evaluated the role of the excitatory and inhibitory neurotransmitter receptors and neuronal synapses in the auditory cortex (AC) injury after blast exposure. Results: We observed sustained elevated ABR thresholds in animals exposed to blast shock waves, while only transient ABR threshold shifts were observed in the impulsive noise group solely at the acute time point. These changes were in concert with the increased expression of ribbon synapses, which is suggestive of neuroinflammation and cellular energy metabolic disorder. It was also found that the onset of tinnitus was accompanied by anxiety, depression-like symptoms, and altered sleep patterns. By comparing the effects of shock wave exposure and impulsive noise exposure, we unveiled that the shock wave exerted more significant effects on tinnitus induction and sensorineural impairments when compared to impulsive noise. Conclusions: In this study, we systematically studied the auditory system structural and functional changes after blast injury, providing more significant insights into the pathophysiology of blast-induced tinnitus. Full article

Background: Vestibular schwannomas (VS) are benign intracranial tumors caused by loss of function of the merlin tumor suppressor. We tested three hypotheses related to radiation, hearing loss (HL), and VS cell survival: (1) radiation causes HL by injuring auditory hair cells (AHC), (2) fractionation reduces radiation-induced HL, and (3) single fraction and equivalent appropriately dosed multi-fractions are equally effective at controlling VS growth. We investigated the effects of single fraction and hypofractionated radiation on hearing thresholds in rats, cell death pathways in rat cochleae, and viability of human merlin-deficient Schwann cells (MD-SC). Methods: Adult rats received cochlear irradiation with single fraction (0 to 18 Gray [Gy]) or hypofractionated radiation. Auditory brainstem response (ABR) testing was performed for 24 weeks. AHC viabilities were determined using immunohistochemistry. Neonatal rat cochleae were harvested after irradiation, and gene- and cell-based assays were conducted. MD-SCs were irradiated, and viability assays and immunofluorescence for DNA damage and cell cycle markers were performed. Results: Radiation caused dose-dependent and progressive HL in rats and AHC losses by promoting expression of apoptosis-associated genes and proteins. When compared to 12 Gy single fraction, hypofractionation caused smaller ABR threshold and pure tone average shifts and was more effective at reducing MD-SC viability. Conclusions: Investigations into the mechanisms of radiation ototoxicity and VS radiobiology will help determine optimal radiation regimens and identify potential therapies to mitigate radiation-induced HL and improve VS tumor control. Full article

Endogenous glucocorticoids (GC) are known to modulate basic elements of cochlear physiology. These include both noise-induced injury and circadian rhythms. While GC signaling in the cochlea can directly influence auditory transduction via actions on hair cells and spiral ganglion neurons, evidence also indicates that GC signaling exerts effects via tissue homeostatic processes that can include effects on cochlear immunomodulation. GCs act at both the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). Most cell types in the cochlea express both receptors sensitive to GCs. The GR is associated with acquired sensorineural hearing loss (SNHL) through its effects on both gene expression and immunomodulatory programs. The MR has been associated with age-related hearing loss through dysfunction of ionic homeostatic balance. Cochlear supporting cells maintain local homeostatic requirements, are sensitive to perturbation, and participate in inflammatory signaling. Here, we have used conditional gene manipulation techniques to target Nr3c1 (GR) or Nr3c2 (MR) for tamoxifen-induced gene ablation in Sox9-expressing cochlear supporting cells of adult mice to investigate whether either of the receptors sensitive to GCs plays a role in protecting against (or exacerbating) noise-induced cochlear damage. We have selected mild intensity noise exposure to examine the role of these receptors related to more commonly experienced noise levels. Our results reveal distinct roles of these GC receptors for both basal auditory thresholds prior to noise exposure and during recovery from mild noise exposure. Prior to noise exposure, auditory brainstem responses (ABRs) were measured in mice carrying the floxed allele of interest and the Cre recombinase transgene, but not receiving tamoxifen injections (defined as control (no tamoxifen treatment), versus conditional knockout (cKO) mice, defined as mice having received tamoxifen injections. Results revealed hypersensitive thresholds to mid- to low-frequencies after tamoxifen-induced GR ablation from Sox9-expressing cochlear supporting cells compared to control (no tamoxifen) mice. GR ablation from Sox9-expressing cochlear supporting cells resulted in a permanent threshold shift in mid-basal cochlear frequency regions after mild noise exposure that produced only a temporary threshold shift in both control (no tamoxifen) f/fGR:Sox9iCre⁺ and heterozygous f/+GR:Sox9iCre⁺ tamoxifen-treated mice. A similar comparison of basal ABRs measured in control (no tamoxifen) and tamoxifen-treated, floxed MR mice prior to noise exposure indicated no difference in baseline thresholds. After mild noise exposure, MR ablation was initially associated with a complete threshold recovery at 22.6 kHz by 3 days post-noise. Threshold continued to shift to higher sensitivity over time such that by 30 days post-noise exposure the 22.6 kHz ABR threshold was 10 dB more sensitive than baseline. Further, MR ablation produced a temporary reduction in peak 1 neural amplitude one day post-noise. While supporting cell GR ablation trended towards reducing numbers of ribbon synapses, MR ablation reduced ribbon synapse counts but did not exacerbate noise-induced damage including synapse loss at the experimental endpoint. GR ablation from the targeted supporting cells increased the basal resting number of Iba1-positive (innate) immune cells (no noise exposure) and decreased the number of Iba1-positive cells seven days following noise exposure. MR ablation did not alter innate immune cell numbers at seven days post-noise exposure. Taken together, these findings support differential roles of cochlear supporting cell MR and GR expression at basal, resting conditions and especially during recovery from noise exposure. Full article

Intraoperative auditory brainstem response (ioABR) testing following tympanostomy tube (TT) placement may be biased due to temporary threshold shifts (TTS). The purpose of the study was to assess the evidence for TTS in children who have undergone ioABR using prolonged latencies of wave I (males > 1.95 ms, females > 1.88 ms) as a marker of a persisting air–bone gap. Eighty-three children underwent ioABR following surgical procedures at University Hospital Bonn, Germany. The primary outcome measure was the latency of wave I at 80-dB SPL. The total sample consisted of 66 males (79.5%) and 17 females (20.5%) with a mean (SD) age of 46.4 (26.6) months. Of 163 operated ears (83 children), 72 (44.2%) had no middle ear fluid, 19 (11.6%) serous fluid, and 72 (44.2%) mucoid fluid. The risk of having a prolonged latency of wave I at 80-dB SPL was OR 4.61 (95% CI 2.01–10.59; p < 0.001) in those with mucoid fluid as compared to those without mucoid fluid. Intraoperative ABR results should account for sex differences and be interpreted with caution and be verified. Ultimately, parents should be engaged in a preoperative discussion to decide if an ioABR should be postponed if mucoid fluid was found. Full article

Kanamycin and cisplatin are ototoxic drugs. The mechanisms are incompletely known. With subcutaneous kanamycin (400 mg/kg, 15 days), auditory threshold shifts were detected at days 12–13 at 16 and 32 kHz, extending to 8 and 4 kHz at days 14–15. The outer hair cell (OHC) loss was concentrated past day 12. The maximum cochlear length showing apoptotic cells, tested with TUNEL, was at day 13. At day 15, 1/5 of the apical cochlea contained preserved OHCs. 3-nitrotyrosine (3-NT) immunolabeling, showing oxidative stress, was found in surviving OHCs and in basal and middle portions of the stria vascularis (SV). The antioxidant Gpx1 gene expression was decreased. The immunocytochemistry showed diminished Gpx1 in OHCs. With intraperitoneal cisplatin (16 mg/kg, single injection), no evoked auditory activity was recorded at the end of treatment, at 72 h. The basal third of the cochlea lacked OHCs. Apoptosis occupied the adjacent 1/3, and the apical third contained preserved OHCs. 3-NT immunolabeling was extensive in OHCs and the SV. Gpx1 and Sod1 gene expression was downregulated. Gpx1 immunostaining diminished in middle and basal SV. More OHCs survived cisplatin than kanamycin towards the apex, despite undetectable evoked activity. Differential regulation of antioxidant enzyme levels suggests differences in the antioxidant response for both drugs. Full article

Introduction: During cochlear implantation, electrode insertion can cause cochlear damage, inflammation, and apoptosis, which can affect the residual hearing. Nanoparticles are increasingly studied as a way to increase the availability of inner ear protective factors. We studied the effect on rats of Pluronic-coated gold nanoparticles (Plu-AuNPs) containing dexamethasone, which were applied locally in the rat’s middle ear following the implant procedure. Methods: Seven rats were used in the study. The right ear served as a model for the Dex-Plu-AuNP group. Following the intracochlear dummy electrode insertion through the round window, Dex-Plu-AuNPs were placed in the round window niche. In the right ear, following the same insertion procedure, free dexamethasone (Dex) was placed in the same manner. Auditory brainstem response thresholds (click stimulus, pure tones at 8 kHz, 16 kHz, 24 kHz, and 32 kHz) were measured before and one week after the procedure. A two-tailed T-test was used for the variables. Statistical significance was set as p < 0.05. Results: In the Dex-Plu-AuNP group, the threshold shift was less than that in the free dexamethasone group, but no statistical significance was noted between the groups. When compared individually, only the 8 kHz frequency showed statistically significant, better results after one week, in favor of the Dex-Plu-AuNP group. The mean postoperative 8 kHz threshold in the Dex-Plu-AuNPs was significantly lower than that of the control group (p = 0.048, t-test). For the other frequencies, statistical analysis showed no significant differences between the mean threshold shifts of the two cohorts. Conclusions: The local application of Plu-AuNPs containing dexamethasone following cochlear implantation may better protect the residual hearing than dexamethasone alone, but a larger sample size is needed to reach a possible statistical significance. Dex-Plu-AuNPs do not seem to cause ototoxicity and may be used as a carrier for other agents. In a clinical setting, Dex-Plu-AuNPs may have the effect of protecting lower frequencies in patients with partial deafness who are candidates for electric acoustic stimulation (EAS). If we consider this tendency, Dex-Plu-AuNPs may also be beneficial for patients with Ménière’s disease. Full article

Congenital unilateral sensorineural hearing loss (uSNHL) is associated with speech-language delays and academic difficulties. Yet, controversy exists in the choice of diagnosis and intervention methods. A cross-sectional prospective design was used to study hearing loss cause in twenty infants with congenital uSNHL consecutively recruited from a universal neonatal hearing-screening program. All normal-hearing ears showed ≤20 dB nHL auditory brainstem response (ABR) thresholds (ABRthrs). The impaired ear median ABRthr was 55 dB nHL, where 40% had no recordable ABRthr. None of the subjects tested positive for congenital cytomegalovirus (CMV) infection. Fourteen subjects agreed to participate in magnetic resonance imaging (MRI). Malformations were common for all degrees of uSNHL and found in 64% of all scans. Half of the MRIs demonstrated cochlear nerve aplasia or severe hypoplasia and 29% showed inner ear malformations. Impaired ear and normal-hearing ear ABR input/output functions on a group level for subjects with ABRthrs < 90 dB nHL were parallel shifted. A significant difference in interaural acoustic reflex thresholds (ARTs) existed. In congenital uSNHL, MRI is powerful in finding a possible hearing loss cause, while congenital CMV infection may be relatively uncommon. ABRs and ARTs indicated an absence of loudness recruitment, with implications for further research on hearing devices. Full article

The decision of whether to perform cochlear implantation is crucial because implantation cannot be reversed without harm. The aim of the study was to compare model-predicted time–place representations of auditory nerve (AN) firing rates for normal hearing and impaired hearing with a view towards personalized indication of cochlear implantation. AN firing rates of 1024 virtual subjects with a wide variety of different types and degrees of hearing impairment were predicted. A normal hearing reference was compared to four hearing prosthesis options, which were unaided hearing, sole acoustic amplification, sole electrical stimulation, and a combination of the latter two. The comparisons and the fitting of the prostheses were based on a ‘loss of action potentials’ (LAP) score. Single-parameter threshold analysis suggested that cochlear implantation is indicated when more than approximately two-thirds of the inner hair cells (IHCs) are damaged. Second, cochlear implantation is also indicated when more than an average of approximately 12 synapses per IHC are damaged due to cochlear synaptopathy (CS). Cochlear gain loss (CGL) appeared to shift these thresholds only slightly. Finally, a support vector machine predicted the indication of a cochlear implantation from hearing loss parameters with a 10-fold cross-validated accuracy of 99.2%. Full article

Cochlear synaptopathy refers to a subclinical hearing pathology which could potentially explain hearing difficulties within the normal hearing threshold; it is also called “hidden hearing loss”. We hypothesized that a temporary threshold shift in sudden sensorineural hearing loss (ISSNHL) also affects the function in the synapse. The aim of the study was to evaluate the presence of cochlear synaptopathy in patients who had completely recovered from unilateral SSNHL Nineteen patients who had completely recovered from ISSNHL from January 2018 to June 2021 were assessed. Complete recovery was established by pure tone audiometry (PTA) 3 months after treatment, according to the American Academy of Otolaryngology–Head and Neck Surgery criteria. Subjects completed the pure tone audiometry, speech audiometry and auditory brain stem response (ABR) test, and completed a questionnaire regarding hearing loss after hearing recovery. The ABR amplitudes of wave I and wave V, and the ratio of wave I/V of both ears (recovered side and healthy side) were assessed. A visual analog scale (VAS) and a hidden hearing loss questionnaire were used to evaluate subjective hearing difficulty. The ABR waves I of the recovered ears had a significantly lower amplitude (p = 0.002) than those of the healthy side, whereas there was no difference in wave V (p = 0.985) or in the ratio of wave I/V (p = 0.107). Some patients still felt mild hearing difficulty although their PTA results were normal, but there was no clear relationship between the VAS score, wave I amplitude and speech recognition scores. The present findings point to the possible existence of cochlear synaptopathy in ears that have completely recovered from unilateral sudden sensorineural hearing loss. We suggest that the causes of cochlear synaptopathy and of idiopathic sudden hearing loss may have something in common. Full article