Evidence of noise-induced subclinical hearing loss using auditory brainstem responses and objective measures of noise exposure in humans

AbstractDamage to the cochlear sensory epithelium is a key contributor to noise-induced sensorineural hearing loss (SNHL). KCNQ4 plays an important role in the cochlear potassium circulation and outer hair cells survival. As miR-153 can target and regulate KCNQ4, we sought to study the role of miR-153 in SNHL. 12-week-old male CBA/J mice were exposed to 2–20 kHz broadband noise at 96 dB SPL to induce temporary threshold shifts and 101 dB SPL to induce permanent threshold shifts. Hearing loss was determined by auditory brainstem responses (ABR). Relative expression of miR-153 and KCNQ4 in mice cochlea were determined by Real-Time quantitative PCR. miR-153 mimics were co-transfected with wild type or mutated KCNQ4 into HEK293 cells. Luciferase reporter assay was used to validate the binding between miR-153 and KCNQ4. AAV-sp-153 was constructed and administrated intra-peritoneally 24- and 2-h prior and immediately after noise exposure to knockdown miR-153. The KCNQ4 is mainly expressed in outer hair cells (OHCs). We showed that the expression of KCNQ4 in mice cochlea was reduced and miR-153 expression was significantly increased after noise exposure compared to control. miR-153 bound to 3′UTR of KNCQ4, and the knockdown of miR-153 with the AAV-sp-153 administration restored KCNQ4 mRNA and protein expression. In addition, the knockdown of miR-153 reduced ABR threshold shifts at 8, 16, and 32 kHz after permanent threshold shifts (PTS) noise exposure. Correspondingly, OHC losses were attenuated with inhibition of miR-153. This study demonstrates that miR-153 inhibition significantly restores KNCQ4 in cochlea after noise exposure, which attenuates SNHL. Our study provides a new potential therapeutic target in the prevention and treatment of SNHL.

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The DNA methylation inhibitor RG108 protects against noise-induced hearing loss

Cell Biology and Toxicology ◽

10.1007/s10565-021-09596-y ◽

2021 ◽

Author(s):

Zhiwei Zheng ◽

Shan Zeng ◽

Chang Liu ◽

Wen Li ◽

Liping Zhao ◽

...

Keyword(s):

Dna Methylation ◽

Hearing Loss ◽

Dna Methyltransferase ◽

Noise Exposure ◽

Auditory Brainstem ◽

Auditory Brainstem Responses ◽

Dna Methyltransferase 1 ◽

Noise Induced Hearing Loss ◽

Threshold Elevation ◽

Whole Mount

Abstract Background Noise-induced hearing loss represents a commonly diagnosed type of hearing disability, severely impacting the quality of life of individuals. The current work is aimed at assessing the effects of DNA methylation on noise-induced hearing loss. Methods Blocking DNA methyltransferase 1 (DNMT1) activity with a selective inhibitor RG108 or silencing DNMT1 with siRNA was used in this study. Auditory brainstem responses were measured at baseline and 2 days after trauma in mice to assess auditory functions. Whole-mount immunofluorescent staining and confocal microcopy of mouse inner ear specimens were performed to analyze noise-induced damage in cochleae and the auditory nerve at 2 days after noise exposure. Results The results showed that noise exposure caused threshold elevation of auditory brainstem responses and cochlear hair cell loss. Whole-mount cochlea staining revealed a reduction in the density of auditory ribbon synapses between inner hair cells and spiral ganglion neurons. Inhibition of DNA methyltransferase activity via a non-nucleoside specific pharmacological inhibitor, RG108, or silencing of DNA methyltransferase-1 with siRNA significantly attenuated ABR threshold elevation, hair cell damage, and the loss of auditory synapses. Conclusions This study suggests that inhibition of DNMT1 ameliorates noise-induced hearing loss and indicates that DNMT1 may be a promising therapeutic target. Graphical abstract

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Effect of Electroacupuncture on Noise-Induced Hearing Loss in Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/9114676 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Chia-Hao Chang ◽

Chia-Der Lin ◽

Ching-Liang Hsieh

Keyword(s):

Hearing Loss ◽

Noise Exposure ◽

Histopathological Examination ◽

Spiral Ganglion ◽

Auditory Brainstem ◽

Auditory Threshold ◽

Auditory Brainstem Responses ◽

Control Group ◽

Noise Induced Hearing Loss ◽

Ganglion Neurons

Acupuncture has long been used to relieve some inner ear diseases such as deafness and tinnitus. The present study examined the effect of electroacupuncture (EA) on noise-induced hearing loss (NIHL) in animals. A NIHL rat model was established. Electroacupuncture pretreatment at 2 Hz or posttreatment at the right Zhongzhu (TE3) acupoint was applied for 1 hour. Auditory thresholds were measured using auditory brainstem responses (ABRs), and histopathology of the cochlea was examined. The results indicated that the baseline auditory threshold of ABR was not significantly different between the control (no noise), EA-only (only EA without noise), noise (noise exposure only), pre-EA (pretreating EA then noise), and post-EA (noise exposure then posttreating with EA) groups. Significant auditory threshold shifts were found in the noise, pre-EA, and post-EA groups in the immediate period after noise exposure, whereas auditory recovery was better in the pre-EA and post-EA groups than that in the noise group at the three days, one week (W1), two weeks (W2), three weeks (W3), and four weeks(W4) after noise stimulation. Histopathological examination revealed greater loss of the density of spiral ganglion neurons in the noise group than in the control group at W1 and W2. Although significant loss of spiral ganglion loss happened in pre-EA and post-EA groups, such loss was less than the loss of the noise group, especially W1. These results indicate that either pretreatment or posttreatment with EA may facilitate auditory recovery after NIHL. The detailed mechanism through which EA alleviates NIHL requires further study.

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Strain Comparison in Rats Differentiates Strain-Specific from More General Correlates of Noise-Induced Hearing Loss and Tinnitus

Journal of the Association for Research in Otolaryngology ◽

10.1007/s10162-021-00822-2 ◽

2021 ◽

Author(s):

L. Koch ◽

B. H. Gaese ◽

Manuela Nowotny

Keyword(s):

Hearing Loss ◽

Noise Exposure ◽

Auditory Brainstem ◽

Specific Pattern ◽

Auditory Brainstem Responses ◽

Sprague Dawley ◽

Rat Strains ◽

Long Evans ◽

Underlying Mechanisms ◽

Strain Dependent

AbstractExperiments in rodent animal models help to reveal the characteristics and underlying mechanisms of pathologies related to hearing loss such as tinnitus or hyperacusis. However, a reliable understanding is still lacking. Here, four different rat strains (Sprague Dawley, Wistar, Long Evans, and Lister Hooded) underwent comparative analysis of electrophysiological (auditory brainstem responses, ABRs) and behavioral measures after noise trauma induction to differentiate between strain-dependent trauma effects and more consistent changes across strains, such as frequency dependence or systematic temporal changes. Several hearing- and trauma-related characteristics were clearly strain-dependent. Lister Hooded rats had especially high hearing thresholds and were unable to detect a silent gap in continuous background noise but displayed the highest startle amplitudes. After noise exposure, ABR thresholds revealed a strain-dependent pattern of recovery. ABR waveforms varied in detail among rat strains, and the difference was most prominent at later peaks arising approximately 3.7 ms after stimulus onset. However, changes in ABR waveforms after trauma were small compared to consistent strain-dependent differences between individual waveform components. At the behavioral level, startle-based gap-prepulse inhibition (gap-PPI) was used to evaluate the occurrence and characteristics of tinnitus after noise exposure. A loss of gap-PPI was found in 33% of Wistar, 50% of Sprague Dawley, and 75% of Long Evans rats. Across strains, the most consistent characteristic was a frequency-specific pattern of the loss of gap-PPI, with the highest rates at approximately one octave above trauma. An additional range exhibiting loss of gap-PPI directly below trauma frequency was revealed in Sprague Dawley and Long Evans rats. Further research should focus on these frequency ranges when investigating the underlying mechanisms of tinnitus induction.

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Comparing the electrophysiological effects of traumatic noise exposure between rodents

Journal of Neurophysiology ◽

10.1152/jn.00081.2021 ◽

2022 ◽

Author(s):

Lenneke Kiefer ◽

Lisa Koch ◽

Melisa Merdan-Desik ◽

Bernhard H. Gaese ◽

Manuela Nowotny

Keyword(s):

Hearing Loss ◽

Noise Exposure ◽

Temporal Dynamics ◽

Auditory Pathway ◽

Auditory Brainstem ◽

Individual Variability ◽

Rodent Species ◽

Waveform Analysis ◽

Auditory Brainstem Responses ◽

Noise Induced Hearing Loss

Noise-induced hearing deficits are important health problems in the industrialized world. As the underlying physiological dysfunctions are not well understood, research in suitable animal models is urgently needed. Three rodent species (Mongolian gerbil, rat and mouse) were studied to compare the temporal dynamics of noise-induced hearing loss after identical procedures of noise exposure. Auditory brainstem responses (ABRs) were measured before, during and up to eight weeks after noise exposure for threshold determination and ABR waveform analysis. Trauma induction with stepwise increasing sound pressure level was interrupted by five interspersed ABR measurements. Comparing short- and long-term dynamics underlying the following noise-induced hearing loss revealed diverging time courses between the three species. Hearing loss occurred early on during noise exposure in all three rodent species at or above trauma frequency. Initial noise level (105 dB SPL) was most effective in rats while the delayed level-increase to 115 dB SPL affected mice much stronger. Induced temporary threshold shifts in rats and mice were larger in animals with lower pre-trauma ABR thresholds. The increase in activity (gain) along the auditory pathway was derived by comparing the amplitudes of short- and long-latency ABR waveform components. Directly after trauma, significant effects were found for rats (decreasing gain) and mice (increasing gain) while gerbils revealed high individual variability in gain changes. Taken together, our comparative study revealed pronounced species-specific differences in the development of noise-induced hearing loss and the related processing along the auditory pathway.

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Effects of Presbycusis and Other Types of Hearing Loss on Auditory Brainstem Responses

International Journal of Audiology ◽

10.3109/14992028609042141 ◽

1986 ◽

Vol 15 (4) ◽

pp. 179-185

Author(s):

Ulf Rosenhall ◽

Kai Pedersen ◽

Mats Dotevall

Keyword(s):

Hearing Loss ◽

Auditory Brainstem ◽

Auditory Brainstem Responses

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Hearing recovery from deafness caused by bromate intoxication

The Journal of Laryngology & Otology ◽

10.1017/s0022215118002001 ◽

2018 ◽

Vol 132 (11) ◽

pp. 1039-1041 ◽

Cited By ~ 1

Author(s):

J Suzuki ◽

Y Takanashi ◽

A Koyama ◽

Y Katori

Keyword(s):

Hearing Loss ◽

Sensorineural Hearing Loss ◽

Pure Tone ◽

Pure Tone Audiometry ◽

Auditory Brainstem ◽

Sensorineural Hearing ◽

Auditory Brainstem Responses ◽

Common Symptom ◽

Hearing Recovery ◽

Continuous Haemodiafiltration

AbstractObjectivesSodium bromate is a strong oxidant, and bromate intoxication can cause irreversible severe-to-profound sensorineural hearing loss. This paper reports the first case in the English literature of bromate-induced hearing loss with hearing recovery measured by formal audiological assessment.Case reportA 72-year-old woman was admitted to hospital with complaints of profound hearing loss, nausea, diarrhoea and anuria after bromate ingestion in a suicide attempt. On admission, pure tone audiometry and auditory brainstem responses showed profound bilateral deafness. Under the diagnosis of bromate-induced acute renal failure and sensorineural hearing loss, continuous haemodiafiltration was performed. When dialysis was discontinued, pure tone audiometry and auditory brainstem responses showed partial threshold recovery from profound deafness.ConclusionSevere-to-profound sensorineural hearing loss is a common symptom of bromate intoxication. Bromate-induced hearing loss may be partially treated, and early application of continuous haemodiafiltration might be useful as a treatment for this intractable condition.

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Auditory Brainstem Responses in a Case of High-Frequency Conductive Hearing Loss

Journal of Speech and Hearing Disorders ◽

10.1044/jshd.5004.346 ◽

1985 ◽

Vol 50 (4) ◽

pp. 346-350 ◽

Cited By ~ 8

Author(s):

Michael P. Gorga ◽

Jan K. Reiland ◽

Kathryn A. Beauchaine

Keyword(s):

Hearing Loss ◽

High Frequency ◽

Conductive Hearing Loss ◽

Auditory Brainstem ◽

Intensity Function ◽

Auditory Brainstem Responses ◽

Normal Limits ◽

Interpeak Latency ◽

Lower Limits ◽

Conductive Hearing

Click-evoked auditory brainstem responses were measured in a patient with high-frequency conductive hearing loss. As is typical in cases of conductive hearing loss, Wave I latency was prolonged beyond normal limits. Interpeak latency differences were just below the lower limits of the normal range. The Wave V latency-intensity function, however was abnormally steep. This pattern is explained by the hypothesis that the slope of the latency-intensity function is determined principally by the configuration of the hearing loss. In cases of high-frequency hearing loss (regardless of the etiology), the response may be dominated by more apical regions of the cochlea at lower intensities and thus have a longer latency.

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