Prevention of Noise-Induced Hearing Loss In Vivo: Continuous Application of Insulin-like Growth Factor 1 and Its Effect on Inner Ear Synapses, Auditory Function and Perilymph Proteins.

As noise-induced hearing loss (NIHL) is a leading cause of occupational diseases, there is an urgent need for the development of preventive and therapeutic interventions. To avoid user-compliance-based problems occurring with conventional protection devices, the pharmacological prevention is currently in the focus of hearing research. Noise exposure leads to an increase in reactive oxygen species (ROS) in the cochlea. This way antioxidant agents are a promising option for pharmacological interventions. Previous animal studies reported preventive as well as therapeutic effects of Insulin-like growth factor 1 (IGF-1) in the context of NIHL. Unfortunately, in patients the time point of the noise trauma cannot always be predicted, and additive effects may occur. Therefore, continuous prevention seems to be beneficial. The present study aimed to investigate the preventive potential of continuous administration of low concentrations of IGF-1 to the inner ear in an animal model of NIHL. Guinea pigs were unilaterally implanted with an osmotic minipump. One week after surgery they received noise trauma, inducing a temporary threshold shift. Continuous IGF-1 delivery lasted for seven more days. It did not lead to significantly improved hearing thresholds compared to control animals. Quite the contrary, there is a hint for a higher noise susceptibility. Nevertheless, changes in the perilymph proteome indicate a reduced damage and better repair mechanisms through the IGF-1 treatment. Thus, future studies should investigate delivery methods enabling continuous prevention but reducing the risk of an overdosage.

[Often not considered during Expert opinion: Patients after accidents or noise traumata - A patient-focused, complementary perspective]. / Bei der Begutachtung oft nicht bedacht: Unfallpatienten und Patienten nach einem Lärmtrauma ­ Eine patientenzugewandte, komplementäre Sichtweise.

Patients who have acquired tinnitus in the context of an accident, a noise trauma or other external influences have important distinctive features in treatment. Although their suffering was in general caused by external circumstances or other people and mostly without own fault, they suffer from a permanent damage, difficult to be realized externally. Additionally they must concentrate their remaining resources to deal adequately with their suffering from tinnitus and very often permanent hearing loss. Legal disputes and the assessment processes necessary in this context can have an unfavorable and perpetuating effect. These influences and patient's reception is laid down here.

[Study protocol of the monocentric prospective randomized placebo-controlled double-blind phase II study to explore the protective effects of the ginkgo biloba extract EGb 761® from temporary noise-induced hearing loss]. / Prüfplan für die monozentrische prospektive randomisierte placebokontrollierte doppelblinde Phase-II-Studie zur Exploration protektiver Effekte des Ginkgo-biloba-Spezialextrakts EGb 761® vor einer vorübergehenden Hörschädigung durch Lärm.

BACKGROUND: Hearing loss is frequently induced by occupational noise exposure and leads to rising hearing thresholds as well as reduced otoacoustic emissions (OAE), mostly caused by metabolic hair cell decompensation. OBJECTIVE: Primary endpoint is the increase in average pure tone thresholds after noise exposure, secondary endpoints are loss of distortion product and click-evoked OAE as well as reduction of their contralateral suppression. PARTICIPANTS AND METHODS: The present study design describes the verification of the anti-oxidant and neuroprotective properties of EGb 761® by evaluation of cochlear protection from noise impact as well as its safety and tolerance in 202 healthy male participants distributed equally to verum and placebo groups in a double-blind manner. Participants were assessed, medicated, exposed to noise, and then examined at timepoints up to 10 min and 4 weeks thereafter. CONCLUSION: This summary of the verification study protocol highlights the complexity of diligent and precise planning according to the European Medicines Agency criteria for controlled trials (EudraCT). Key points are the intervention rationale, definitions of in- and exclusion criteria, estimation of subject numbers, and examination method setting in terms of optimum endpoint description.

An unusual case of sudden sensorineural hearing loss after cycling class.

In this case report, our patient developed sudden sensorineural hearing loss (SSNHL) after loud noise exposure during a popular cardiovascular group exercise cycling class. To increase awareness among all healthcare professionals of the effects of these modern-day group fitness classes on hearing loss, we describe this case and review the current literature on SSNHL and its management. A 35-year old man developed SSNHL in the setting of loud noise exposure during a high intensity aerobic exercise class. After a short course of oral steroids with no improvement, intratympanic steroids were administered weekly for three weeks. The patient showed minimal improvement; thus, hyperbaric oxygen therapy was conducted. Serial audiograms continued to show severe to profound mixed hearing loss in the right ear. In conclusion, individuals who participate in loud, high-intensity aerobic group-exercise classes should be careful of the potential for noise-induced hearing loss. Aerobic exercise may make these individuals more susceptible to noise-induced hearing loss. Early intervention is critical for any chance of recovery.

The use of nonhuman primates in studies of noise injury and treatment.

Exposure to prolonged or high intensity noise increases the risk for permanent hearing impairment. Over several decades, researchers characterized the nature of harmful noise exposures and worked to establish guidelines for effective protection. Recent laboratory studies, primarily conducted in rodent models, indicate that the auditory system may be more vulnerable to noise-induced hearing loss (NIHL) than previously thought, driving renewed inquiries into the harmful effects of noise in humans. To bridge the translational gaps between rodents and humans, nonhuman primates (NHPs) may serve as key animal models. The phylogenetic proximity of NHPs to humans underlies tremendous similarity in many features of the auditory system (genomic, anatomical, physiological, behavioral), all of which are important considerations in the assessment and treatment of NIHL. This review summarizes the literature pertaining to NHPs as models of hearing and noise-induced hearing loss, discusses factors relevant to the translation of diagnostics and therapeutics from animals to humans, and concludes with some of the practical considerations involved in conducting NHP research.

Noise-induced hearing loss: Translating risk from animal models to real-world environments.

Noise-induced hearing loss (NIHL) is a common injury for service members and civilians. Effective prevention of NIHL with drug agents would reduce the prevalence of NIHL. There are a host of challenges in translation of investigational new drug agents from animals into human clinical testing, however. Initial articles in this special issue describe common pre-clinical (animal) testing paradigms used to assess potential otoprotective drug agents and design-related factors that impact translation of promising agents into human clinical trials. Additional articles describe populations in which NIHL has a high incidence and factors that affect individual vulnerability. While otoprotective drugs will ultimately be developed for use by specific noise-exposed populations, there has been little effort to develop pre-clinical (animal) models that accurately model exposure hazards across diverse human populations. To facilitate advances in the translational framework for NIHL otoprotection in pre-clinical and clinical testing, the overarching goals of the current series are to (1) review the animal models that have been used, highlighting the relevance to the human populations of interest, (2) provide insight into the populations for whom pharmaceutical interventions might, or might not, be appropriate, and (3) highlight the factors that drive the significant individual variability observed in humans.

Molecular Structure and Regulation of P2X Receptors With a Special Emphasis on the Role of P2X2 in the Auditory System.

The P2X purinergic receptors are cation-selective channels gated by extracellular adenosine 5'-triphosphate (ATP). These purinergic receptors are found in virtually all mammalian cell types and facilitate a number of important physiological processes. Within the past few years, the characterization of crystal structures of the zebrafish P2X4 receptor in its closed and open states has provided critical insights into the mechanisms of ligand binding and channel activation. Understanding of this gating mechanism has facilitated to design and interpret new modeling and structure-function experiments to better elucidate how different agonists and antagonists can affect the receptor with differing levels of potency. This review summarizes the current knowledge on the structure, activation, allosteric modulators, function, and location of the different P2X receptors. Moreover, an emphasis on the P2X2 receptors has been placed in respect to its role in the auditory system. In particular, the discovery of three missense mutations in P2X2 receptors could become important areas of study in the field of gene therapy to treat progressive and noise-induced hearing loss. J. Cell. Physiol. 231: 1656-1670, 2016. © 2015 Wiley Periodicals, Inc.

Effect of repetitive transcranial magnetic stimulation on auditory function following acoustic trauma.

Repetitive transcranial magnetic stimulation (rTMS) is one form of non-invasive brain stimulation and increasingly shows neuroprotection in multiple neurological disorders. However, the potential of rTMS for protective action on auditory function following acoustic trauma has not been investigated. Here, we examined effect of TMS on hearing conservation, neurons survival and brain-derived neurotrophin factor (BDNF) expression in the cochlea and auditory cortex following acoustic trauma in rats. Wistar rats were exposed to intense pure tone noise (10 kHz, 120 dB SPL for 2 h) followed by rTMS treatment or sham treatment (handling control) daily for 14 days. Auditory brainstem response revealed there was no significant difference in hearing threshold shifts between rTMS- and sham-treated rats, although rTMS-treated rats showed less neuron loss in the auditory cortex in comparison with sham rats. Additionally, acoustic trauma increased BDNF expression in the cochlea and auditory cortex, and this elevation could be attenuated by rTMS treatment. Our results suggest present regiment of rTMS does not protect hearing against acoustic trauma, but maybe have implications for tinnitus treatment.

Acute acoustic trauma: how to manage and how to prevent?

INTRODUCTION: The consequence of an exposure to intense sounds can be a temporary or permanent hearing loss and even with a rapid therapeutic management, severe sensorineural sequelae may persist. METHODS: the authors report a retrospective study about 64 patients followed for an acute acoustic trauma during a period of 8 years (2006 to 2013). For all the cases, a clinical examination associated to a pure-tone audiometry was conducted. Hearing levels were measured at the frequencies 500, 1000, 2000 and 3000 Hertz. Auditory evoked potentials were performed in 17 cases. The therapeutic and evolutive data were detailed and discussed. RESULTS: All our patients were male with a mean age of 34 years. The cause of acoustic trauma was a firing of a gun near the ear in 48 cases, an explosion near the ear in 5 cases and a sudden exposure to loud noises near military planes in 11 cases. Clinical complaints were acute hearing loss with tinnitus. Audiometric exams found a sensorineural hearing loss with a hearing level average of 38 decibels (dB) +/- 14 SD. The therapy consisted of systemic cortisteroids associated in all the cases to peripheral vasodilators.  It was given intravenously during 10 days and then orally with vasodilators during one to 3 months. Hyperbaric oxygenotherapy have been administrated for 25 patients. The follow-up consisted of questioning about symptoms, clinical examination and pure-tone audiometry. A good evolution was noted in 52 cases (81%) and the mean of hearing level after therapy was: 24 dB +/- 12 dB. Despite a prolonged therapy with vaso-active drugs, tinnitus persisted in 36 cases. CONCLUSION: Controlling noise and its harmful effects through technical devices and safety professionals programs are the best way to reduce the frequency and the sensorineural sequelae due to acute acoustic trauma.

Efficiency of hyperbaric oxygen and steroid therapy in treatment of hearing loss following acoustic trauma.

INTRODUCTION: Most commonly used treatment modalities for acute acoustic trauma (AAT) include steroid and hyperbaric oxygen (HBO2) therapy. The aim of this study is to investigate the effectiveness of combined steroid and HBO2 therapy in patients who develop AAT during firearms training and the effect of delay to treatment on treatment success. MATERIALS AND METHODS: Patients admitted with the complaint of hearing loss after firearms training between January 2011 and April 2013 were evaluated retrospectively. Patients were grouped according to date of admission; patients admitted within the first 10 days were included in Group A and those admitted between Days 11 and 30 in Group B. RESULTS: A total of 48 patients (73 ears) with AAT were included. There were 37 ears in Group A and 36 ears in Group B. The number of ears with complete treatment response, partial treatment response and treatment failure (unchanged) were one (2.7%), 7 (18.9%) and 29 (78.4%) in Group A and 0 (0%), 3 (8.3%) and 33 (91.7%) in Group B, respectively. There was no statistically significant difference between the groups (p = 0.095). Late-term results (at Week 6) demonstrated Group A showed higher hearing gain on high frequencies than Group B (p < 0.05), but this result was not consistent with clinical outcome results. CONCLUSION: The success rate of combined HBO2 and steroid therapy was very low in our study. However, early initiation of treatment results in better outcomes. Protective measures have great importance in preventing AAT.

DPOAE level mapping for detecting noise-induced cochlear damage from short-duration music exposures.

Distortion product otoacoustic emission (DPOAE) level mapping provides a comprehensive picture of cochlear responses over a range of DP frequencies and f2/f1ratios. We hypothesized that individuals exposed to high-level sound would show changes detectable by DPOAE mapping, but not apparent on a standard DP-gram. Thirteen normal hearing subjects were studied before and after attending music concerts. Pure-tone audiometry (500-8,000 Hz), DP-grams (0.3-10 kHz) at 1.22 ratio, and DPOAE level maps were collected prior to, as soon as possible after, and the day after the concerts. All maps covered the range of 2,000-6,000 Hz in DP frequency and from 1.3 to -1.3 in ratio using equi-level primary tone stimuli. Changes in the pure-tone audiogram were significant (P ≤ 0.01) immediately after the concert at 1,000 Hz, 4,000 Hz, and 6,000 Hz. The DP-gram showed significant differences only at f2= 4,066 (P = 0.01) and f2= 4,348 (P = 0.04). The postconcert changes were readily apparent both visually and statistically (P ≤ 0.01) on the mean DP level maps, and remained statistically significantly different from baseline the day after noise exposure although no significant changes from baseline were seen on the DP-gram or audiogram the day after exposure. Although both the DP-gram and audiogram showed recovery by the next day, the average DPOAE level maps remained significantly different from baseline. The mapping data showed changes in the cochlea that were not detected from the DP-gram obtained at a single ratio. DPOAE level mapping provides comprehensive information on subtle cochlear responses, which may offer advantages for studying and tracking noise-induced hearing loss (NIHL).

Hearing in young adults. Part I: The effects of attitudes and beliefs toward noise, hearing loss, and hearing protector devices.

There is great concern regarding the development of noise-induced hearing loss (NIHL) in youth caused by high sound levels during various leisure activities. Health-orientated behavior of young adults might be linked to the beliefs and attitudes toward noise, hearing loss, and hearing protector devices (HPDs). The objective of the current study was to evaluate the effects of attitudes and beliefs toward noise, hearing loss, and HPDs on young adults' hearing status. A questionnaire and an audiological test battery were completed by 163 subjects (aged 18-30 years). The questionnaire contained the Youth Attitude to Noise Scale (YANS) and Beliefs about Hearing Protection and Hearing Loss (BAHPHL). A more positive attitude or belief represented an attitude where noise or hearing loss is seen as unproblematic and attitudes and beliefs regarding HPDs is worse. Hearing was evaluated using (high frequency) pure tone audiometry (PTA), transient evoked and distortion product otoacoustic emissions. First, mean differences in hearing between the groups with different attitudes and beliefs were evaluated using one-way analysis of variance (ANOVA). Second, a χ² test was used to examine the usage of HPDs by the different groups with different attitudes and beliefs. Young adults with a positive attitude had significantly more deteriorated hearing and used HPDs less than the other subjects. Hearing conservation programs (HCPs) for young adults should provide information and knowledge regarding noise, hearing loss, and HPDs. Barriers wearing HPDs should especially be discussed. Further, those campaigns should focus on self-experienced hearing related symptoms that might serve as triggers for attitudinal and behavioral changes.

Hearing in young adults. Part II: The effects of recreational noise exposure.

Great concern arises from recreational noise exposure, which might lead to noise-induced hearing loss in young adults. The objective of the current study was to evaluate the effects of recreational noise exposure on hearing function in young adults. A questionnaire concerning recreational noise exposures and an audiological test battery were completed by 163 subjects (aged 18-30 years). Based on the duration of exposure and self-estimated loudness of various leisure-time activities, the weekly and lifetime equivalent noise exposure were calculated. Subjects were categorized in groups with low, intermediate, and high recreational noise exposure based on these values. Hearing was evaluated using audiometry, transient-evoked otoacoustic emissions (TEOAEs), and distortion-product otoacoustic emissions (DPOAEs). Mean differences in hearing between groups with low, intermediate, and high recreational noise exposure were evaluated using one-way analysis of variance (ANOVA). There were no significant differences in hearing thresholds, TEOAE amplitudes, and DPOAE amplitudes between groups with low, intermediate, or high recreational noise exposure. Nevertheless, one-third of our subjects exceeded the weekly equivalent noise exposure for all activities of 75 dBA. Further, the highest equivalent sound pressure levels (SPLs) were calculated for the activities visiting nightclubs or pubs, attending concerts or festivals, and playing in a band or orchestra. Moreover, temporary tinnitus after recreational noise exposure was found in 86% of our subjects. There were no significant differences in hearing between groups with low, intermediate, and high recreational noise exposure. Nevertheless, a long-term assessment of young adults' hearing in relation to recreational noise exposure is needed.

Therapeutic potential of a gamma-secretase inhibitor for hearing restoration in a guinea pig model with noise-induced hearing loss.

BACKGROUND: Notch signaling plays a crucial role in the fate determination of cochlear progenitor cells, hair cells, and supporting cells in the developing cochlea. Recent studies have demonstrated the temporal activation of Notch signaling in damaged mature cochleae, and have demonstrated the induction of new hair cells by pharmacologically inhibiting Notch signaling. The present study aimed to illustrate the feasibility of pharmacologically inhibiting Notch signaling by using a gamma-secretase inhibitor for treating sensorineural hearing loss. RESULTS: The effect of the sustained local delivery of MDL28170, a gamma-secretase inhibitor, on hearing and hair cell induction was tested in a guinea pig model with noise-induced hearing loss. MDL28170 was directly delivered into the cochlear fluids via a micro-osmotic pump. Drug application was initiated 7 days after noise exposure. Measurements of auditory brainstem responses revealed better hearing in the MDL28170-treated animals than in the vehicle controls. Histological analysis demonstrated a higher number of outer hair cells in the MDL28170-treated cochleae than the vehicle-treated cochleae. CONCLUSION: These findings strongly suggest that local sustained delivery of a gamma-secretase inhibitor into the cochlea could be a novel strategy for treating acute hearing loss that is refractory to conventional treatment.

[Acute acoustic trauma, a retrospective analysis about 225 military cases]. / Traumatismes sonores aigus: analyse rétrospective de 225 cas militaires.

OBJECTIVES: Studying the epidemiology, the evolutionary audiometric profile and the after-effects of acute acoustic trauma managed in military environment. Assessing the influence beyond the audiometric recovery of earplugs, precocity of the treatment and hyperbaric oxygen therapy. MATERIALS AND METHODS: This retrospective cohort gathered 225 military cases of acute acoustic trauma hospitalized between 2003 and 2008. The cochlear supportive therapy associated intravenous methyl-prednisolone and pentoxyfilline, completed sometimes with hyperbaric oxygen therapy. The evolution was appreciated with pure-tone audiometry at the admission, at the end of hospitalization and one month after. Perceptive deafness and recovery shifts were statically calculated on 109 ears. RESULTS: On the 225 cases, 90% were males, middle-aged of 23 years. Initially 95% of the patients complained about tinnitus, associated with hearing loss felt for 71%. The left ear was more frequently affected. The initial audiometric loss was average of 34 dB HL, concentrated on 4000 and 6000 Hz frequencies. The therapy allowed an average recovery of +18,3 dB in a month. The audiometric sequela concerned 40% of the cases, and residual tinnitus a third. These rates were significantly higher with people whose initial hearing loss average exceeded 40 dB HL. Concerning the audiometric recovery and the after-effects, no significantly difference was found between the groups treated before or after 12 hours. There were either no difference with the earplugs and hyperbaric oxygen groups. CONCLUSION: Despite the effectiveness of early corticotherapy, after-effects of acute acoustic trauma remain frequent and invalidating. Its prevention suffers from non-observance and malposition of earplugs.

[Clinical analysis of using hyperbaric oxygen comprehensive therapy for the treatment of 110 cases noise induced deafness].

OBJECTIVE: To observe the clinical effects of using hyperbaric oxygen comprehensive therapy for the treatment of noise induced deafness. METHODS: From May 2009 to April 2012 in our hospital 220 cases of noise induced deafness patients were chosen and they were all construction workers; According to different treatments all patients were divided into the control group (110 cases) only having hyperbaric oxygen treatment and the treatment group (110 cases) using hyperbaric oxygen comprehensive therapy, including control group simply by. Hearing improvements of the two groups were recorded and compared. RESULTS: The cure rate of the comprehensive therapy group was 53.6%which was higher than that of the control group 38.2% (χ(2) = 5.290, P < 5.290), while the total effective rate of the comprehensive therapy group was 79.1%which was also significantly higher than that of the control group 67.3% (χ(2) = 3.914, P < 0.05). After two courses of comprehensive treatment the cure rate and total effective rate were 47.3%and 73.6%respectively, while after four courses of comprehensive treatment group the cure rate and total effective rate turned to be 60.9% and 84.5% respectively, which had significant difference (χ(2) values were 4.118 and 3.958, P < 0.05). CONCLUSIONS: The cure rate and total effective rate of the comprehensive therapy group are higher than the simple hyperbaric oxygen treatment group, which is worthy of clinical application and promotion in the future.

Analysis of Therapeutic Options for Noise-Induced Hearing Loss: Retroauricular Injection of Methylprednisolone Sodium Succinate Combined with Hyperbaric Oxygenation.

OBJECTIVE: To evaluate the clinical effect of retroaural injection of methylprednisolone sodium succinate combined with hyperbaric oxygen (HBO) on the treatment of noise-induced hearing loss. METHODS: Case data of 220 patients with hearing loss treated at the Zhongda Hospital Southeast University from January 1, 2019 to August 1, 2023 were obtained. As per the treatment plan, the recruited patients were divided into two cohorts: 158 cases in the combined-treatment group (retroaural injection of methylprednisolone sodium succinate combined with HBO) and 62 cases in the single-hormone group (retroaural injection of methylprednisolone sodium succinate). Comparison of the clinical efficacies and postoperative complication rates of the two groups was performed after treatment. MS-Excel was used to build a database for all data, and SPSS26.0 was utilized in the statistical analysis of recorded data. RESULTS: For patients with low-frequency, high-frequency, and flat descending type, the combined-treatment group showed significantly higher clinical effective rate than the single-hormone group (P < 0.05). For patients with disease duration ≤7 days, the combined-treatment group attained a significantly higher clinical effective rate was than the single-hormone group (P < 0.05). The safety of patients in both groups was evaluated mainly through their adverse reactions. The total incidence of adverse reactions in the single-hormone group reached 9.68%, and that in the combined-treatment group was 8.23%. The two groups revealed no significant difference in terms of incidence of adverse reactions (P > 0.05). CONCLUSION: HBO combined with retroaural injection of methylprednisolone sodium succinate has good clinical efficacy and safety in the treatment of hearing loss.

Military aircrew and noise-induced hearing loss: prevention and management.

Modern-day high performance aircraft are more powerful, more efficient, and, unfortunately, frequently produce high noise levels, resulting in noise-induced hearing loss (NIHL) in military aircrew. Military pilots are required to perform many flight duties correctly in the midst of many challenges that may affect mission completion as well as aircraft and aircrew safety. NIHL can interfere with successful mission completion. NIHL may also require aircrew to be downgraded from flying duties, with the incumbent re-training costs for downgraded personnel and training costs for new/replacement aircrew. As it is not possible to control the source of the noise without compromising the efficiency of the engine and aircraft, protecting the aircrew from hazards of excessive noise and treating NIHL are of extreme importance. In this article we discuss various personal hearing protection devices and their efficacy, and pharmacological agents for prevention and management of NIHL.