Recovery rate after acute acoustic trauma: a case series and meta-analysis.

OBJECTIVE: Steroids given systemically, locally, or both are the mainstay of treatment for acute acoustic trauma (AAT). The overall recovery rate (full, partial, and none) is undetermined. STUDY DESIGN: Original case series and systematic literature review. SETTING: Case series of a tertiary referral center and a systematic literature review. METHODS: Cases of AAT between 2012 and 2022 were retrospectively analyzed for demographics, acoustic trauma characteristics, treatment modality and delay and prognosis. This case series was added to the series identified by a systematic literature review. This review included "Medline" via "PubMed", "EMBASE", and "Google scholar". All series were pooled for meta-analysis defining prognosis following steroidal treatment for AAT patients. RESULTS: The pooled analyses included 662 ears, out of which 250 underwent complete recovery of hearing (overall proportion = 0.2809, 95%confidence interval [CI] = 0.1611-0.4178). Any recovery was recorded for 477 ears (overall proportion = 0.7185, 95% CI = 0.5671-0.8493) and no recovery was documented for 185 ears (overall proportion = 0.2815, 95% CI = 0.1507-0.4329). CONCLUSION: The rate of overall recovery for AAT is around 70%, and around 30% for full recovery when steroids are initiated within the first 2 weeks following the insult.

Cochlear protection against noise exposure requires serotonin type 3A receptor via the medial olivocochlear system.

The cochlear efferent feedback system plays important roles in auditory processing, including regulation of the dynamic range of hearing, and provides protection against acoustic trauma. These functions are performed through medial olivocochlear (MOC) neurons. However, the underlying cellular and molecular mechanisms are not fully understood. The serotonin type 3A (5-HT3A) receptor is widely expressed throughout the nervous system, which suggests important roles in various neural functions. However, involvement of the 5-HT3A receptor in the MOC system remains unclear. We used mice in this study and found that the 5-HT3A receptor was expressed in MOC neurons that innervated outer hair cells in the cochlea and was involved in the activation of MOC neurons by noise exposure. 5-HT3A receptor knockout impaired MOC functions, potentiated noise-induced hearing loss, and increased loss of ribbon synapses following noise exposure. Furthermore, 5-HT3 receptor agonist treatment alleviated the noise-induced hearing loss and loss of ribbon synapses, which enhanced cochlear protection provided by the MOC system. Our findings demonstrate that the 5-HT3A receptor plays fundamental roles in the MOC system and critically contributes to protection from noise-induced hearing impairment.

Efficacy of Oral Steroids for Acute Acoustic Trauma.

OBJECTIVE: This study aimed to study the effect of steroid treatment on new-onset sensorineural hearing loss (SNHL) in subjects presenting shortly after an audiometry-confirmed acute acoustic trauma (AAT) injury. STUDY DESIGN: This is a case-control study. METHODS: We identified healthy military personnel who presented with AAT injury to the Israeli Defense Forces Medical Corps Otolaryngology/Audiology Services during 2016-2020. Patients were nonrandomly allocated to a treatment arm, where they received steroids (prednisone, 1 mg/kg, 60 mg maximal daily dose), administered for either ≥7 days or <7 days, or to a control arm, in which no treatment was offered besides loud noise avoidance. Audiometries were conducted within 7 days following the AAT and within 1 month later. We compared changes in bone conduction (BC) and air conduction (AC) thresholds at 2-8 kHz. RESULTS: Of the 263 enrolled subjects, 137 (52%) received steroids and 126 (48%) received no treatment. Subjects who were treated early (<24 h) with high-dose steroids and for ≥7 days demonstrated significantly better hearing outcomes, compared with the nontreatment group. Subjects in the steroids group demonstrated 13-14 dB average improvement in BC thresholds at 3 and 4 kHz (p = 0.001) and additional 7-8 dB average improvement in AC thresholds at 6 and 8 kHz, compared with the nontreatment group (p < 0.0001). These observations were more compelling in patients who initially presented with worse hearing losses (>35 dB). No statistically significant differences were observed in AC/BC pure tone average between the two groups. CONCLUSIONS: Early oral steroids are recommended in AAT injuries and were shown to improve hearing outcomes within 1 month.

Change in gene expression levels of GABA, glutamate and neurosteroid pathways due to acoustic trauma in the cochlea.

The characteristic feature of noise-induced hearing loss (NIHL) is the loss or malfunction of the outer hair cells (OHC) and the inner hair cells (IHC) of the cochlea. 90-95% of the spiral ganglion neurons, forming the cell bodies of cochlear nerve, synapse with the IHCs. Glutamate is the most potent excitatory neurotransmitter for IHC-auditory nerve synapses. Excessive release of glutamate in response to acoustic trauma (AT), may cause excitotoxicity by causing damage to the spiral ganglion neurons (SGN) or loss of the spiral ganglion dendrites, post-synaptic to the IHCs. Another neurotransmitter, GABA, plays an important role in the processing of acoustic stimuli and central regulation after peripheral injury, so it is potentially related to the regulation of hearing function and sensitivity after noise. The aim of this study is to evaluate the effect of AT on the expressions of glutamate excitotoxicity, GABA inhibition and neurosteroid synthesis genes.We exposed 24 BALB/c mice to AT. Controls were sacrificed without exposure to noise, Post-AT(1) and Post-AT(15) were sacrificed on the 1st and 15th day, respectively, after noise exposure. The expressions of various genes playing roles in glutamate, GABA and neurosteroid pathways were compared between groups by real-time PCR.Expressions of Cyp11a1, Gls, Gabra1, Grin2b, Sult1a1, Gad1, and Slc1a2 genes in Post-AT(15) mice were significantly decreased in comparison to control and Post-AT(1) mice. No significant differences in the expression of Slc6a1 and Slc17a8 genes was detected.These findings support the possible role of balance between glutamate excitotoxicity and GABA inhibition is disturbed during the post AT days and also the synthesis of some neurosteroids such as pregnenolone sulfate may be important in this balance.

High Blood Glucose Levels Affect Auditory Brainstem Responses after Acoustic Overexposure in Rats.

INTRODUCTION: Diabetes mellitus (DM) is a systemic disease characterized by hyperglycemia and several pathological changes. DM-related hearing dysfunctions are associated with histological changes. Here, we explore hearing function and synaptic changes in the inner hair cells (IHCs) of rats with streptozotocin (STZ)-induced diabetes. METHODS: STZ was injected to trigger diabetes. Rats with DM were exposed to narrow-band noise (105 dB SPL) for 2 h, and hearing function was analyzed 1, 3, 7, and 14 days later. Both the hearing threshold and the peak 1 amplitude of the tone auditory brainstem response were assessed. After the last functional test, animals were sacrificed for histological evaluation. RESULTS: We found no changes in the baseline hearing threshold; however, the peak 1 amplitude at the low frequency (4 kHz) was significantly higher in both DM groups than in the control groups. The hearing threshold had not fully recovered at 14 days after diabetic rats were exposed to noise. The peak 1 amplitude at the higher frequencies (16 and 32 kHz) was significantly larger in both DM groups than in the control groups. The histological analysis revealed that the long-term DM group had significantly more synapses in the 16 kHz region than the other groups. CONCLUSIONS: We found that high blood glucose levels increased peak 1 amplitudes without changing the hearing threshold. Diabetic rats were less resilient in threshold changes and were less vulnerable to peak 1 amplitude and synaptic damage than control animals.

Effect and Biocompatibility of a Cross-Linked Hyaluronic Acid and Polylactide-co-glycolide Microcapsule Vehicle in Intratympanic Drug Delivery for Treating Acute Acoustic Trauma.

The treatment of acute hearing loss is clinically challenging due to the low efficacy of drug delivery into the inner ear. Local intratympanic administration of dexamethasone (D) and insulin-like growth factor 1 (IGF1) has been proposed for treatment, but they do not persist in the middle ear because they are typically delivered in fluid form. We developed a dual-vehicle drug delivery system consisting of cross-linked hyaluronic acid and polylactide-co-glycolide microcapsules. The effect and biocompatibility of the dual vehicle in delivering D and IGF1 were evaluated using an animal model of acute acoustic trauma. The dual vehicle persisted 10.9 times longer (8.7 days) in the middle ear compared with the control (standard-of-care vehicle, 0.8 days). The dual vehicle was able to sustain drug release over up to 1 to 2 months when indocyanine green was loaded as the drug. One-third of the animals experienced an inflammatory adverse reaction. However, it was transient with no sequelae, which was validated by micro CT findings, endoscopic examination, and histological assessment. Hearing restoration after acoustic trauma was satisfactory in both groups, which was further supported by comparable numbers of viable hair cells. Overall, the use of a dual vehicle for intratympanic D and IGF1 delivery may maximize the effect of drug delivery to the target organ because the residence time of the vehicle is prolonged.

Specific loss of neural sensitivity to interaural time difference of unmodulated noise stimuli following noise-induced hearing loss.

Sensorineural hearing loss (SNHL) causes an overall deficit in binaural hearing, including the abilities to localize sound sources, discriminate interaural time and level differences (ITDs and ILDs, respectively), and utilize binaural cues to aid signal detection and comprehension in noisy environments. Few studies have examined the effect of SNHL on binaural coding in the central auditory system, and those that have focused on age-related hearing loss. We induced hearing loss in male and female Dutch-belted rabbits via noise overexposure and compared unanesthetized single-unit responses of their inferior colliculi [hearing loss (HL) neurons] with those of unexposed rabbits. Sound-level thresholds of HL neurons to diotic noise were elevated by 75 dB, on average. Sensitivity of firing rates of HL neurons to the azimuth of a broadband noise stimulus was reduced, on average, but was confounded by differences in sound level with respect to detection threshold between groups. We independently manipulated ITD and ILD in virtual acoustic space and found directional sensitivity in binaurally sensitive HL neurons was entirely due to ILD sensitivity and no different than that for unexposed rabbits. However, ITD sensitivity was completely absent in binaurally sensitive HL neurons for noise stimuli both in virtual acoustic space and with ITDs extending to ±3 ms. HL neurons also had weaker spike-timing precision and slightly increased spontaneous rates. Overall, ILD sensitivity was uncompromised, whereas ITD sensitivity was completely lost, implying a specific inability to use information in the timing or correlation of acoustic noise waveforms between the two ears following severe SNHL.NEW & NOTEWORTHY Sensorineural hearing loss compromises perceptual abilities that arise from hearing with two ears, yet its effects on binaural aspects of neural responses are largely unknown. We found that, following severe hearing loss because of acoustic trauma, auditory midbrain neurons specifically lost the ability to encode time differences between the arrival of a broadband noise stimulus to the two ears, whereas the encoding of sound level differences between the two ears remained uncompromised.

Pathology and mechanisms of cochlear aging.

Presbycusis, or age-related hearing loss (ARHL), occurs in most mammals with variations in the age of onset, rate of decline, and magnitude of degeneration in the central nervous system and inner ear. The affected cochlear structures include the stria vascularis and its vasculature, spiral ligament, sensory hair cells and auditory neurons. Dysfunction of the stria vascularis results in a reduced endocochlear potential. Without this potential, the cochlear amplification provided by the electro-motility of the outer hair cells is insufficient, and a high-frequency hearing-loss results. Degeneration of the sensory cells, especially the outer hair cells also leads to hearing loss due to lack of amplification. Neuronal degeneration, another hallmark of ARHL, most likely underlies difficulties with speech discrimination, especially in noisy environments. Noise exposure is a major cause of ARHL. It is well-known to cause sensory cell degeneration, especially the outer hair cells at the high frequency end of the cochlea. Even loud, but not uncomfortable, sound levels can lead to synaptopathy and ultimately neuronal degeneration. Even in the absence of a noisy environment, aged cells degenerate. This pathology most likely results from damage to mitochondria and contributes to degenerative changes in the stria vascularis, hair cells, and neurons. The genetic underpinnings of ARHL are still unknown and most likely involve various combinations of genes. At present, the only effective strategy for reducing ARHL is prevention of noise exposure. If future strategies can improve mitochondrial activity and reduce oxidative damage in old age, these should also bring relief.

Biocompatibility and Therapeutic Effect of 3 Intra-Tympanic Drug Delivery Vehicles in Acute Acoustic Trauma.

INTRODUCTION: The aim of this study was to assess the biocompatibility of several intra-tympanic (IT) drug delivery vehicles and to compare hearing outcomes. MATERIALS AND METHODS: After acute acoustic trauma, rats were treated with IT 10 mg/mL dexamethasone phosphate (D) and divided into the following groups for drug delivery: saline + D (n = 15), hyaluronic acid (HA) + D (n = 17), and methoxy polyethylene glycol-b-polycaprolactone block copolymer (MP) + D (n = 24). RESULTS: No inflammation was found in the saline + D or HA + D groups. The duration of vehicle/drug persistence in the bulla was significantly longer for the MP + D (47.5 days) and HA + D groups (1.8 days) than for the saline + D group (<1 day). The tympanic membrane was significantly thicker in the MP + D group than in the saline + D and HA + D groups. The proportion of ears with good hearing outcome was significantly higher (63.6%) in the HA + D group than in the MP + D group. The number of hair cells in the hearing loss (HL) control group was significantly lower than in the MP + D group. DISCUSSION/CONCLUSION: HA shows great potential as a biocompatible vehicle for D delivery via the IT route, without an inflammatory reaction and with better hearing outcomes. Considering inflammation and hearing, MP may not be a good candidate for IT drug delivery.

[Modern approaches and prospective directions in treatment of acute sensorineural hearing loss following acoustic trauma]. / Sovremennye podkhody i perspektivnye napravleniya v lechenii ostroi sensonevral'noi tugoukhosti akutravmaticheskogo geneza.

The article presents a review of the literature on the treatment of acute sensorineural hearing loss, acoustic trauma in people exposed to impulse noise. Groups of the most used drugs for the pharmacological correction of hearing impairment in this pathology are present, such as glucocorticosteroids, antioxidants, nootropics, antihypoxants, and others, are covered. Particular attention is paid to use of drugs taking into account the main links of pathogenesis.

Enhancement of the Medial Olivocochlear System Prevents Hidden Hearing Loss.

Cochlear synaptopathy produced by exposure to noise levels that cause only transient auditory threshold elevations is a condition that affects many people and is believed to contribute to poor speech discrimination in noisy environments. These functional deficits in hearing, without changes in sensitivity, have been called hidden hearing loss (HHL). It has been proposed that activity of the medial olivocochlear (MOC) system can ameliorate acoustic trauma effects. Here we explore the role of the MOC system in HHL by comparing the performance of two different mouse models: an α9 nicotinic receptor subunit knock-out (KO; Chrna9 KO), which lacks cholinergic transmission between efferent neurons and hair cells; and a gain-of-function knock-in (KI; Chrna9L9'T KI) carrying an α9 point mutation that leads to enhanced cholinergic activity. Animals of either sex were exposed to sound pressure levels that in wild-type produced transient cochlear threshold shifts and a decrease in neural response amplitudes, together with the loss of ribbon synapses, which is indicative of cochlear synaptopathy. Moreover, a reduction in the number of efferent contacts to outer hair cells was observed. In Chrna9 KO ears, noise exposure produced permanent auditory threshold elevations together with cochlear synaptopathy. In contrast, the Chrna9L9'T KI was completely resistant to the same acoustic exposure protocol. These results show a positive correlation between the degree of HHL prevention and the level of cholinergic activity. Notably, enhancement of the MOC feedback promoted new afferent synapse formation, suggesting that it can trigger cellular and molecular mechanisms to protect and/or repair the inner ear sensory epithelium.SIGNIFICANCE STATEMENT Noise overexposure is a major cause of a variety of perceptual disabilities, including speech-in-noise difficulties, tinnitus, and hyperacusis. Here we show that exposure to noise levels that do not cause permanent threshold elevations or hair cell death can produce a loss of cochlear nerve synapses to inner hair cells as well as degeneration of medial olivocochlear (MOC) terminals contacting the outer hair cells. Enhancement of the MOC reflex can prevent both types of neuropathy, highlighting the potential use of drugs that increase α9α10 nicotinic cholinergic receptor activity as a pharmacotherapeutic strategy to avoid hidden hearing loss.

Urocortin 3 signalling in the auditory brainstem aids recovery of hearing after reversible noise-induced threshold shift.

KEY POINTS: Ongoing, moderate noise exposure does not instantly damage the auditory system but may cause lasting deficits, such as elevated thresholds and accelerated ageing of the auditory system. The neuromodulatory peptide urocortin-3 (UCN3) is involved in the body's recovery from a stress response, and is also expressed in the cochlea and the auditory brainstem. Lack of UCN3 facilitates age-induced hearing loss and causes permanently elevated auditory thresholds following a single 2 h noise exposure at moderate intensities. Outer hair cell function in mice lacking UCN3 is unaffected, so that the observed auditory deficits are most likely due to inner hair cell function or central mechanisms. Highly specific, rather than ubiquitous, expression of UCN3 in the brain renders it a promising candidate for designing drugs to ameliorate stress-related auditory deficits, including recovery from acoustic trauma. ABSTRACT: Environmental acoustic noise is omnipresent in our modern society, with sound levels that are considered non-damaging still causing long-lasting or permanent changes in the auditory system. The small neuromodulatory peptide urocortin-3 (UCN3) is the endogenous ligand for corticotropin-releasing factor receptor type 2 and together they are known to play an important role in stress recovery. UCN3 expression has been observed in the auditory brainstem, but its role remains unclear. Here we describe the detailed distribution of UCN3 expression in the murine auditory brainstem and provide evidence that UCN3 is expressed in the synaptic region of inner hair cells in the cochlea. We also show that mice with deficient UCN3 signalling experience premature ageing of the auditory system starting at an age of 4.7 months with significantly elevated thresholds of auditory brainstem responses (ABRs) compared to age-matched wild-type mice. Following a single, 2 h exposure to moderate (84 or 94 dB SPL) noise, UCN3-deficient mice exhibited significantly larger shifts in ABR thresholds combined with maladaptive recovery. In wild-type mice, the same noise exposure did not cause lasting changes to auditory thresholds. The presence of UCN3-expressing neurons throughout the auditory brainstem and the predisposition to hearing loss caused by preventing its normal expression suggests UCN3 as an important neuromodulatory peptide in the auditory system's response to loud sounds.

Seismic air guns damage rock lobster mechanosensory organs and impair righting reflex.

The effects of anthropogenic aquatic noise on marine invertebrates are poorly understood. We investigated the impact of seismic surveys on the righting reflex and statocyst morphology of the palinurid rock lobster, Jasus edwardsii, using field-based exposure to air gun signals. Following exposure equivalent to a full-scale commercial assay passing within 100-500 m, lobsters showed impaired righting and significant damage to the sensory hairs of the statocyst. Reflex impairment and statocyst damage persisted over the course of the experiments-up to 365 days post-exposure and did not improved following moulting. These results indicate that exposure to air gun signals caused morphological damage to the statocyst of rock lobsters, which can in turn impair complex reflexes. This damage and impairment adds further evidence that anthropogenic aquatic noise has the potential to harm invertebrates, necessitating a better understanding of possible ecological and economic impacts.

Regeneration of Cochlear Hair Cells and Hearing Recovery through Hes1 Modulation with siRNA Nanoparticles in Adult Guinea Pigs.

Deafness is commonly caused by the irreversible loss of mammalian cochlear hair cells (HCs) due to noise trauma, toxins, or infections. We previously demonstrated that small interfering RNAs (siRNAs) directed against the Notch pathway gene, hairy and enhancer of split 1 (Hes1), encapsulated within biocompatible poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) could regenerate HCs within ototoxin-ablated murine organotypic cultures. In the present study, we delivered this sustained-release formulation of Hes1 siRNA (siHes1) into the cochleae of noise-injured adult guinea pigs. Auditory functional recovery was measured by serial auditory brainstem responses over a nine-week follow-up period, and HC regeneration was evaluated by immunohistological evaluations and scanning electron microscopy. Significant HC restoration and hearing recovery were observed across a broad tonotopic range in ears treated with siHes1 NPs, beginning at three weeks and extending out to nine weeks post-treatment. Moreover, both ectopic and immature HCs were uniquely observed in noise-injured cochleae treated with siHes1 NPs, consistent with de novo HC production. Our results indicate that durable cochlear HCs were regenerated and promoted significant hearing recovery in adult guinea pigs through reversible modulation of Hes1 expression. Therefore, PLGA-NP-mediated delivery of siHes1 to the cochlea represents a promising pharmacologic approach to regenerate functional and sustainable mammalian HCs in vivo.

Protective and therapeutic effects of milrinone on acoustic trauma in rat cochlea.

OBJECTIVE: The aim of this study was to investigate the potential protective and therapeutic effects of milrinone, a specific phosphodiesterase (PDE) III inhibitor, on acoustic trauma-induced cochlear injury and apoptosis. METHODS: A total number of 30 healthy Wistar albino rats were evenly divided into five groups as follows: group 1 was assigned as control group; group 2 and 3 were assigned as low-dosage groups (0.25 mg/kg) in which milrinone was administered 1 h before acoustic trauma (AT) and 2 h after AT, respectively; group 4 and 5 were assigned as high-dosage groups (0.50 mg/kg) in which the drug was administered 1 h before AT and 2 h after AT, respectively. Except control group, all treatment groups received a single dosage of milrinone for 5 days. Distortion product otoacoustic emissions (DPOAE) measurements were recorded before AT as well as at second and fifth post-traumatic days. At the end of fifth day, all rats were sacrificed and the cochlea of the rats was removed for histopathological evaluation. In addition, the groups were compared in terms of apoptotic index via caspase-3 staining. RESULTS: In terms of signal-to-noise ratio (SNR), there was no statistically significant difference among the groups following AT (p > 0.05). After 5 days of milrinone treatment, the best SNR values were found in group 5, though all groups did not statistically differ (p > 0.05). In histopathological evaluation, vacuolization, inflammation, and edema scores in all treatment groups were statistically lower than those of the control group (p < 0.05). In group 2 and 4 where the drug was administered before AT, the inflammation and apoptosis index was lower than those of group 3 and 5 where the drug was administered after AT (p < 0.0001). CONCLUSION: We reveal that milrinone has a protective effect on cochlear damage in the experimental acoustic model of rats. This protective effect was more apparent following the pre-traumatic milrinone administration, and is associated with its effect on decreasing inflammation and apoptosis. Based on DPOAE measurements following AT, especially in the group 5 (high-dosage group), milrinone may also have a therapeutic effect.

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.

Treatment of military acoustic accidents with N-Acetyl-L-cysteine (NAC).

OBJECTIVE: To study if the antioxidant (AO) N-Acetyl-L-cysteine (NAC) reduces the risk of hearing loss after acoustic accidents in humans. DESIGN: A retrospective, observational study. STUDY SAMPLE: Personnel of the Swedish Armed Forces (SAF) exposed to military acoustic accidents during a 5 year period. Included in the study were 221 cases (mean age: 22.9 years). Most of the exposures, 84%, were weapon related. NAC (400 mg) was given directly after the accident in 146 cases; 75 had not received NAC. RESULTS: The prevalence of hearing thresholds ≥25 dB HL, and the incidence of threshold shifts ≥10 dB, was lower in the NAC group than in the non-NAC group directly after the noise exposure. The deterioration was temporary and not discernable a long time after the accident. The difference was most pronounced in the right ear. The risk reduction to get a temporary hearing loss (TTS), affecting one or both ears was 39% (significant) in the NAC group. CONCLUSIONS: The study has demonstrated a significant reduction of the incidence of TTS by the use of NAC. Since cases of both permanent hearing loss (PTS) and noise-induced tinnitus are recruited from cases with TTS, the demonstrated risk reduction indicates a positive effect of NAC.

Methionine Sulfoxide Reductase A Knockout Mice Show Progressive Hearing Loss and Sensitivity to Acoustic Trauma.

Methionine sulfoxide reductases (MsrA and MsrB) protect the biological activity of proteins from oxidative modifications to methionine residues and are important for protecting against the pathological effects of neurodegenerative diseases. In the current study, we characterized the auditory phenotype of the MsrA knockout mouse. Young MsrA knockout mice showed small high-frequency threshold elevations for auditory brainstem response and distortion product otoacoustic emission compared to those of wild-type mice, which progressively worsened in older MsrA knockout mice. MsrA knockout mice showed an increased sensitivity to noise at young and older ages, suggesting that MsrA is part of a mechanism that protects the cochlea from acoustic damage. MsrA mRNA in the cochlea was increased following acoustic stimulation. Finally, expression of mRNA MsrB1 was compromised at 6 months old, but not in younger MsrA knockout mice (compared to controls). The identification of MsrA in the cochlea as a protective mediator from both early onset hearing loss and acoustic trauma expands our understanding of the pathways that may induce protection from acoustic trauma and foster further studies on how to prevent the damaging effect of noise exposure through Msr-based therapy.

Inner Ear Damage by Firecracker Trauma.

Firecrackers are still popular among the general public of various populations worldwide. This study investigated inner ear damage in patients with firecracker trauma and analyzed noise levels in 6 kinds of commercially available firecrackers. During the past 20 years, we have experienced 30 patients with firecracker trauma. An inner ear test battery comprising audiometry, cervical and ocular vestibular-evoked myogenic potential (cVEMP and oVEMP) tests and a caloric test was performed. The real-time noise levels were measured outdoors at a distance of 2, 4 and 6 m away from a lighting firecracker to mimic a noise event. Mean hearing levels at high frequencies (4,000 and 8,000 Hz) were significantly higher than those at the low and middle frequencies, indicating that firecrackers mostly cause high-tone hearing loss. For the vestibular damage, abnormality percentages were higher in the results of cVEMP (80%) and oVEMP (60%) tests, but not in the caloric test (8%). In conclusion, most firecrackers exhibited noise levels > 110 dB SPL even at a distance of 6 m. This blast injury simultaneously damaged the cochlea, saccule and utricle, but spared the semicircular canals, indicating that blast exposure potentiates the adverse effect of noise exposure on both cochlear and vestibular partitions.

Unmyelinated type II afferent neurons report cochlear damage.

In the mammalian cochlea, acoustic information is carried to the brain by the predominant (95%) large-diameter, myelinated type I afferents, each of which is postsynaptic to a single inner hair cell. The remaining thin, unmyelinated type II afferents extend hundreds of microns along the cochlear duct to contact many outer hair cells. Despite this extensive arbor, type II afferents are weakly activated by outer hair cell transmitter release and are insensitive to sound. Intriguingly, type II afferents remain intact in damaged regions of the cochlea. Here, we show that type II afferents are activated when outer hair cells are damaged. This response depends on both ionotropic (P2X) and metabotropic (P2Y) purinergic receptors, binding ATP released from nearby supporting cells in response to hair cell damage. Selective activation of P2Y receptors increased type II afferent excitability by the closure of KCNQ-type potassium channels, a potential mechanism for the painful hypersensitivity (that we term "noxacusis" to distinguish from hyperacusis without pain) that can accompany hearing loss. Exposure to the KCNQ channel activator retigabine suppressed the type II fiber's response to hair cell damage. Type II afferents may be the cochlea's nociceptors, prompting avoidance of further damage to the irreparable inner ear.