Noise-induced Hidden Hearing Loss Research Articles

Mechanism of noise induced hidden hearing loss based on proteomics

Objective: To explore the mechanism of noise-induced hidden hearing loss by proteomics. Methods: In October 2022, 64 SPF male C57BL/6J mice were divided into control group and noise exposure group with 32 mice in each group according to random sampling method. The noise exposure group was exposed to 100 dB sound pressure level, 2000-16000 Hz broadband noise for 2 h, and the mouse hidden hearing loss model was established. Auditory brainstem response (ABR) was used to test the change of hearing threshold of mice on the 7th day after noise exposure, the damage of basal membrane hair cells was observed by immunofluorescence, and the differentially expressed proteins in the inner ear of mice in each group were identified and analyzed by 4D-Label-free quantitative proteomics, and verified by Western blotting. The results were statistically analyzed by ANOVA and t test. Results: On the 7th day after noise exposure, there was no significant difference in hearing threshold between the control group and the noise exposure group at click and 8000 Hz acoustic stimulation (P>0.05) . The hearing threshold in the noise exposure group was significantly higher than that in the control group under 16000 Hz acoustic stimulation (P<0.05) . Confocal immunofluorescence showed that the basal membrane hair cells of cochlear tissue in noise exposure group were arranged neatly, but the relative expression of C-terminal binding protein 2 antibody of presynaptic membrane in middle gyrus and basal gyrus was significantly lower than that in control group (P<0.05) . GO enrichment analysis showed that the functions of differentially expressed proteins were mainly concentrated in membrane potential regulation, ligand-gated channel activity, and ligand-gated ion channel activity. KEGG pathway enrichment analysis showed that differentially expressed proteins were significantly enriched in phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt) signaling pathway, NOD-like receptor signaling pathway, calcium signaling pathway, etc. Western blotting showed that the expression of inositol 1, 4, 5-trisphosphate receptor 3 (Itpr3) was increased and the expression of solute carrier family 38 member 2 (Slc38a2) was decreased in the noise exposure group (P<0.05) . Conclusion: Through proteomic analysis, screening and verification of the differential expression proteins Itpr3 and Slc38a2 in the constructed mouse noise-induced hidden hearing loss model, the glutaminergic synaptic related pathways represented by Itpr3 and Slc38a2 may be involved in the occurrence of hidden hearing loss.

Analysis of clinical audiological characteristics of noise-induced silent hearing loss

Objective: To explore the characteristics of audiology examination of Noise-Induced Hidden Hearing Loss (NIHHL), and then explore its valuable diagnostic methods.Methods: A total of 80 young men aged between 19 and 35 were selected. They were classified into the experimental group with noise exposure history and the control group without noise exposure history, with 40 men in each group. We carried out extended high-frequency audiometry test for good ears; conducted speech in noise measurement and distortion product emission for good ears; DPOAE test, compare and analyze the results of each test.Results: The extended high frequency hearing threshold test results showed that the hearing threshold of the experimental group was larger than that of the control group at the frequency above 8kHz, with significant statistical difference (p &lt; .01). The results of speech audiometry under noise showed that the signal-to-noise ratio loss in the experimental group was greater than that in the control group, with a significant statistical difference (p &lt; .01). The results of otoacoustic emission showed that the signal-to-noise ratio of the experimental group was lower than that of the control group at the frequency of 6 kHz and above, with a statistically significant difference (p &lt; .01). There is a correlation between pure tone audiometry and DPOAE test results at high frequencies (6 kHz: p &lt;. 0001, r = -.478; 8 kHz: p &lt; .0001, r = -.491;) ; There was a correlation between speech audiometry and DPOAE test results under noise (p = .031, r = -.299).Conclusion: Compared with the control group, the extended high frequency pure tone hearing threshold increased or could not be elicited in the experimental group, speech recognition ability decreased significantly under noise, DPOAE was normally elicited but signal-to-noise ratio decreased, and there was a certain correlation between them. The above three audiological examination methods have a certain reference value for early recognition of hidden hearing loss.

Recommended Auditory Brainstem Responses to Stimulation and Recording Parameters for Hidden Hearing Loss: A Systematic Review and Meta-Analysis

Although a lesion of hidden hearing loss (HHL) has focused on the sprial ganglion, stimulation and recording parameters for auditory brainstem response (ABR) are not yet specific enough to confirm its dysfunction. In the current review, we identify ABR parameters, especially Wave I, for diagnosing HHL through both a systemic review and meta-analysis of 14 articles retrieved from seven journal data bases. The most commonly used parameters were a click or 4 kHz tone burst as the stimulus at a rate of less than 11/sec at more than 80 dB intensity levels with alternating polarity through the ear canal. For quantitative results, our meta-analysis from eight articles demonstrated a significant difference in the overall effect size for amplitude between HHL patients and their counterparts with normal hearing. For the subgroup and its analysis, tone burst and high intensity level revealed significantly lower effect size in HHL patients compared to the control group, whereas the stimuli rate and electrode montage statstically were not statistical significance. Although we examined a small number of studies and their heterogenity, obtaining ABR Wave I was clinically differentiated when noise-induced HHL was considered. We thus suggest that stimulation and recording parameters should be applied to a large number of patients and thereby standardized as sensitive features for Wave I in the clinic.

Morphology changes in the cochlea of impulse noise-induced hidden hearing loss

Background This study was focused on impulse noise induces hidden hearing loss. Objectives This study was designed to determine the morphology changes of noise-induced hidden hearing loss (NIHHL). Method Fifteen guinea pigs were divided into three groups: noise-induced hidden hearing loss (NIHHL) group, noise-induced hearing loss (NIHL) group, and normal control group. For the NIHHL group, guinea pigs were exposed to 15 times of impulse noise with peak intensity of 163 dB SPL at one time. For the NIHL group, animals were exposed to two rounds of 100 times impulse noise, and the time interval is 24 h. Auditory brain response (ABR) was tested before, immediately, 24 h, one week, and one month after noise exposure to evaluate cochlear physiology changes. One month after noise exposure, all guinea pigs in three groups were sacrificed, and basement membranes were carefully dissected immediately after ABR tests. The cochlea samples were observed by transmission electron microscopy (TEM) to find out the morphology changes. Result The ABR results showed that 15 times of impulse noise exposure could cause NIHHL in guinea pigs and 200 times could cause completely hearing loss. Impulse noise exposure could cause a dramatic increase of mitochondria in the inner hair cell. The structures of ribbon synapse and heminode were also obviously impaired compared to the normal group. The nerve fiber and myelin sheath remained intact after impulse noise exposure. Conclusion This research revealed that impulse noise could cause hidden hearing loss, and the changes in inner hair cells, ribbon synapse, and heminode all played a vital role in the pathogenesis of hidden hearing loss.

Involvement of the SIRT1/PGC-1α Signaling Pathway in Noise-Induced Hidden Hearing Loss.

Objective: To establish an animal model of noise-induced hidden hearing loss (NIHHL), evaluate the dynamic changes in cochlear ribbon synapses and cochlear hair cell morphology, and observe the involvement of the SIRT1/PGC-1α signaling pathway in NIHHL. Methods: Male guinea pigs were randomly divided into three groups: control group, noise exposure group, and resveratrol treatment group. Each group was divided into five subgroups: the control group and 1 day, 1 week, 2 weeks, and 1 month post noise exposure groups. The experimental groups received noise stimulation at 105 dB SPL for 2 h. Hearing levels were examined by auditory brainstem response (ABR). Ribbon synapses were evaluated by inner ear basilar membrane preparation and immunofluorescence. The cochlear morphology was observed using scanning electron microscopy. Western blotting analysis and immunofluorescence was performed to assess the change of SIRT1/PGC-1α signaling. Levels of superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), ATP and SIRT1 activity were measured using commercial testing kits. Results: In the noise exposure group, hearing threshold exhibited a temporary threshold shift (TTS), and amplitude of ABR wave I decreased irreversibly. Ribbon synapse density decreased after noise exposure, and the stereocilia were chaotic and then returned to normal. The expression and activity of SIRT1 and PGC-1α protein was lower than that in the control group. SOD, CAT and ATP were also influenced by noise exposure and were lower than those in the control group, but MDA showed no statistical differences compared with the control group. After resveratrol treatment, SIRT1 expression and activity showed a significant increase after noise exposure, compared with the noise exposure group. In parallel, the PGC-1α and antioxidant proteins were also significantly altered after noise exposure, compared with the noise exposure group. The damage to the ribbon synapses and the stereocilia were attenuated by resveratrol as well. More importantly, the auditory function, especially ABR wave I amplitudes, was also promoted in the resveratrol treatment group. Conclusion: The SIRT1/PGC-1α signaling pathway and oxidative stress are involved in the pathogenesis of NIHHL and could be potential therapeutical targets in the future.

Impulse Noise Induced Hidden Hearing Loss, Hair Cell Ciliary Changes and Oxidative Stress in Mice.

Recent studies demonstrated that reversible continuous noise exposure may induce a temporary threshold shift (TTS) with a permanent degeneration of auditory nerve fibers, although hair cells remain intact. To probe the impact of TTS-inducing impulse noise exposure on hearing, CBA/J Mice were exposed to noise impulses with peak pressures of 145 dB SPL. We found that 30 min after exposure, the noise caused a mean elevation of ABR thresholds of ~30 dB and a reduction in DPOAE amplitude. Four weeks later, ABR thresholds and DPOAE amplitude were back to normal in the higher frequency region (8–32 kHz). At lower frequencies, a small degree of PTS remained. Morphological evaluations revealed a disturbance of the stereociliary bundle of outer hair cells, mainly located in the apical regions. On the other hand, the reduced suprathreshold ABR amplitudes remained until 4 weeks later. A loss of synapse numbers was observed 24 h after exposure, with full recovery two weeks later. Transmission electron microscopy revealed morphological changes at the ribbon synapses by two weeks post exposure. In addition, increased levels of oxidative stress were observed immediately after exposure, and maintained for a further 2 weeks. These results clarify the pathology underlying impulse noise-induced sensory dysfunction, and suggest possible links between impulse-noise injury, cochlear cell morphology, metabolic changes, and hidden hearing loss.

RNA-seq Profiling and Co-expression Network Analysis of Long Noncoding RNAs and mRNAs Reveal Novel Pathogenesis of Noise-induced Hidden Hearing Loss

Noise-induced hidden hearing loss (NIHHL), one of the family of conditions described as noise-induced hearing loss (NIHL), is characterized by synaptopathy following moderate noise exposure that causes only temporary threshold elevation. Long noncoding RNAs (lncRNAs) mediate several essential regulatory functions in a wide range of biological processes and diseases, but their roles in NIHHL remain largely unknown. In order to determine the potential roles of these lncRNAs in the pathogenesis of NIHHL, we first evaluated their expression in NIHHL mice model and mapped possible regulatory functions and targets using RNA-sequencing (RNA-seq). In total, we identified 133 lncRNAs and 522 mRNAs that were significantly dysregulated in the NIHHL model. Gene Ontology (GO) showed that these lncRNAs were involved in multiple cell components and systems including synapses and the nervous and sensory systems. In addition, a lncRNA–mRNA network was constructed to identify core regulatory lncRNAs and transcription factors. KEGG analysis was also used to identify the potential pathways being affected in NIHHL. These analyses allowed us to identify the guanine nucleotide binding protein alpha stimulating (GNAS) gene as a key transcription factor and the adrenergic signaling pathway as a key pathway in the regulation of NIHHL pathogenesis. Our study is the first, to our knowledge, to isolate a lncRNA mediated regulatory pathway associated with NIHHL pathogenesis; these observations may provide fresh insight into the pathogenesis of NIHHL and may pave the way for therapeutic intervention in the future.

RNA-Seq Profiling and Co-Expression Network Analysis of lncRNAs and mRNAs Reveal Novel Pathogenesis of Noise-Induced Hidden Hearing Loss

Background: Long noncoding RNAs (lncRNAs) mediate essential epigenetic regulation in a wide range of biological processes and diseases. In this study, we aimed to uncover the novel pathogenesis in noise-induced hidden hearing loss (NIHHL). Methods: We developed murine NIHHL model and murine noise-induced hearing loss (NIHL), respectively. Auditory brainstem response (ABR) were used to detect hearing function. The ribbon synapses alteration was determined by immunofluorescence. We investigated the potential roles of lncRNAs in NIHHL model via second sequencing. LncRNA-mRNA co-expression network were generated to identify lncRNA-expression trend and potential lncRNA target genes. The screened potential target genes were verified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Findings: We identified 71 lncRNAs and 290 mRNAs specifically dysregulated in NIHHL model. Further, an association of lncRNA-mRNA showed that 27 dysregulated lncRNA were successfully predicted an interaction with mRNAs. Finally, a further KEGG analysis showed that 6 signaling pathways were putative pathway in the process of NIHHL, and among them, adrenergic signaling is the most likely pathway. LncRNA Sept7 and mRNA GNAS were found to be able to differentiate NIHHL model from Control Group and NIHL model. Validation of up-regulated of mRNA GNAS and lncRNA Sept7 in NIHHL model compared to Control Group and NIHL model by qRT-PCR. Interpretation: lncRNA Sept7 and mRNA GNAS served a promoter in combination with adrenergic signaling pathway, which might reveal novel pathogenesis of NIHHL and also might be a group of potential biomarkers in the prognosis of NIHHL. Funding Statement: The research was generously funded by [the National Natural Science Foundation of China] under Grant [81830030]; [the National Natural Science Foundation of China] under Grant [81770997]; [the Beijing Science and Technology Commission - Education Commission Joint Fund Project] under Grant [KZ201810025040] and [the National Natural Science Foundation of China] under Grant [81771016]. Declaration of Interests: None of the authors have any relevant conflicts of interests to declare. Ethics Approval Statement: All the experiments and animal welfares were carried out in accordance with National Institute of Health Guide for Care and Use of Laboratory Animals which were revised in 1996. Besides, all the experiments were approved by the animal committee of the Shengjing Hospital of China Medical University (2019PS355K). And all the efforts were aimed to minimize the animals’ suffering and the number of sacrificing mice.

Can You Hear Me Later and Believe Me Now? Behavioral Law and Economics of Chronic Repeated Ambient Acoustic Pollution Causing Noise-Induced (Hidden) Hearing Loss

This Article analyzes the public health issues of Noise-Induced Hearing Loss (NIHL) and Noise-Induced Hidden Hearing Loss (NIHHL) due to Chronic Repeated Ambient Acoustic Pollution (CRAAP). This Article examines the clinical and empirical medical data about NIHL and NIHHL and its normative implications. This Article applies behavioral law and economics and information economics to advocate legal policies to reduce CRAAP. Finally, this Article advocates changing individual and social attitudes about deafness and hearing loss to raise political awareness and social consciousness about NIHL and NIHHL. One way to change our attitudes is by practicing empathy and kindness, including loving kindness mindfulness (LKM) meditation.

Coding-in-Noise Deficits are Not Seen in Responses to Amplitude Modulation in Subjects with cochlear Synaptopathy Induced by a Single Noise Exposure

Since the first report of noise-induced synaptic damage in animals without permanent threshold shifts (PTSs), the concept of noise-induced hidden hearing loss (NIHHL) has been proposed to cover the functional deficits in hearing associated with noise-induced synaptopathy. Moreover, the potential functional deficit associated with the noise-induced synaptopathy has been largely attributed to the loss of auditory nerve fibers (ANFs) with a low spontaneous spike rate (SSR). As this group of ANFs is critical for coding at suprathreshold levels and in noisy background, coding-in-noise deficit (CIND) has been considered to be main consequence of the synaptopathy. However, such deficits have not been verified after a single, brief exposure to noise without PTS. In the present study, synaptopathy was generated by such noise exposure in both mice and guinea pigs. Responses to amplitude modulation (AM) were recorded at a high sound level in combination with masking to evaluate the existence of CINDs that might be associated with loss of low-SSR ANFs. An overall reduction in response amplitude was seen in AM-evoked compound action potential (CAP). However, no such reduction was seen in the scalp-recorded envelope following response (EFR), suggesting a compensation due to increased central gain. Moreover, there was no significant difference in masking effect between the control and noise groups. The results suggest that either there is no significant CIND after the synaptopathy we created, or the AM response tested with our protocol was not sufficiently sensitive to detect such a deficit; far-field EFR is not sensitive to cochlear pathology.

Coding Deficits in Noise-Induced Hidden Hearing Loss May Stem from Incomplete Repair of Ribbon Synapses in the Cochlea.

Recent evidence has shown that noise-induced damage to the synapse between inner hair cells (IHCs) and type I afferent auditory nerve fibers (ANFs) may occur in the absence of permanent threshold shift (PTS), and that synapses connecting IHCs with low spontaneous rate (SR) ANFs are disproportionately affected. Due to the functional importance of low-SR ANF units for temporal processing and signal coding in noisy backgrounds, deficits in cochlear coding associated with noise-induced damage may result in significant difficulties with temporal processing and hearing in noise (i.e., “hidden hearing loss”). However, significant noise-induced coding deficits have not been reported at the single unit level following the loss of low-SR units. We have found evidence to suggest that some aspects of neural coding are not significantly changed with the initial loss of low-SR ANFs, and that further coding deficits arise in association with the subsequent reestablishment of the synapses. This suggests that synaptopathy in hidden hearing loss may be the result of insufficient repair of disrupted synapses, and not simply due to the loss of low-SR units. These coding deficits include decreases in driven spike rate for intensity coding as well as several aspects of temporal coding: spike latency, peak-to-sustained spike ratio and the recovery of spike rate as a function of click-interval.

Cochlear Synaptopathy and Noise-Induced Hidden Hearing Loss.

Recent studies on animal models have shown that noise exposure that does not lead to permanent threshold shift (PTS) can cause considerable damage around the synapses between inner hair cells (IHCs) and type-I afferent auditory nerve fibers (ANFs). Disruption of these synapses not only disables the innervated ANFs but also results in the slow degeneration of spiral ganglion neurons if the synapses are not reestablished. Such a loss of ANFs should result in signal coding deficits, which are exacerbated by the bias of the damage toward synapses connecting low-spontaneous-rate (SR) ANFs, which are known to be vital for signal coding in noisy background. As there is no PTS, these functional deficits cannot be detected using routine audiological evaluations and may be unknown to subjects who have them. Such functional deficits in hearing without changes in sensitivity are generally called “noise-induced hidden hearing loss (NIHHL).” Here, we provide a brief review to address several critical issues related to NIHHL: (1) the mechanism of noise induced synaptic damage, (2) reversibility of the synaptic damage, (3) the functional deficits as the nature of NIHHL in animal studies, (4) evidence of NIHHL in human subjects, and (5) peripheral and central contribution of NIHHL.