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

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1880
Author(s):  
Paul Gratias ◽  
Jamal Nasr ◽  
Corentin Affortit ◽  
Jean-Charles Ceccato ◽  
Florence François ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Hair Cells ◽  
Impulse Noise ◽  
Noise Exposure ◽  
Morphological Changes ◽  
Nerve Fibers ◽  
Outer Hair Cells ◽  
Hidden Hearing Loss ◽  
The Impact

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.

Morphology Changes in the Cochlea of Impulse Noiseinduced Hidden Hearing Loss

2021 ◽  
Author(s):  
Guo-wei Qi ◽  
Lei Shi ◽  
Han-dai Qin ◽  
Yuhua Zhu ◽  
Qing-qing Jiang ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Guinea Pigs ◽  
Impulse Noise ◽  
Noise Exposure ◽  
Nerve Fibers ◽  
Basement Membranes ◽  
Time Interval ◽  
Noise Induced Hearing Loss ◽  
Hidden Hearing Loss ◽  
Morphology Changes

Abstract 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 noise-induced hidden hearing loss group, the guinea pigs were exposed to 15 times of impulse noise at one time. For the noise-induced hearing loss group, the animals were exposed to a total of 200 times of impulse noise in two times, and the time interval is 24 hours. Auditory brain response (ABR) was tested before, immediately, 24h, 1week, 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 found out the monograph 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 in chondriosome in the inner hair cell. The structures of ribbon synapses and heminodes were also obviously impaired compared to the normal group. The nerve fibers and myelin sheaths remained intact after impulse noise exposure. Conclusion: This research revealed for the first time 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.

scholarly journals Primed to die: an investigation of the genetic mechanisms underlying noise-induced hearing loss and cochlear damage in homozygous Foxo3-knockout mice

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Holly J. Beaulac ◽  
Felicia Gilels ◽  
Jingyuan Zhang ◽  
Sarah Jeoung ◽  
Patricia M. White
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Noise Exposure ◽  
Multiphoton Microscopy ◽  
Cell Loss ◽  
Outer Hair Cells ◽  
Noise Induced Hearing Loss ◽  
Knock Out ◽  
Cell Death Pathway ◽  
Cochlear Damage

AbstractThe prevalence of noise-induced hearing loss (NIHL) continues to increase, with limited therapies available for individuals with cochlear damage. We have previously established that the transcription factor FOXO3 is necessary to preserve outer hair cells (OHCs) and hearing thresholds up to two weeks following mild noise exposure in mice. The mechanisms by which FOXO3 preserves cochlear cells and function are unknown. In this study, we analyzed the immediate effects of mild noise exposure on wild-type, Foxo3 heterozygous (Foxo3+/−), and Foxo3 knock-out (Foxo3−/−) mice to better understand FOXO3’s role(s) in the mammalian cochlea. We used confocal and multiphoton microscopy to examine well-characterized components of noise-induced damage including calcium regulators, oxidative stress, necrosis, and caspase-dependent and caspase-independent apoptosis. Lower immunoreactivity of the calcium buffer Oncomodulin in Foxo3−/− OHCs correlated with cell loss beginning 4 h post-noise exposure. Using immunohistochemistry, we identified parthanatos as the cell death pathway for OHCs. Oxidative stress response pathways were not significantly altered in FOXO3’s absence. We used RNA sequencing to identify and RT-qPCR to confirm differentially expressed genes. We further investigated a gene downregulated in the unexposed Foxo3−/− mice that may contribute to OHC noise susceptibility. Glycerophosphodiester phosphodiesterase domain containing 3 (GDPD3), a possible endogenous source of lysophosphatidic acid (LPA), has not previously been described in the cochlea. As LPA reduces OHC loss after severe noise exposure, we treated noise-exposed Foxo3−/− mice with exogenous LPA. LPA treatment delayed immediate damage to OHCs but was insufficient to ultimately prevent their death or prevent hearing loss. These results suggest that FOXO3 acts prior to acoustic insult to maintain cochlear resilience, possibly through sustaining endogenous LPA levels.

A Review of Gunshot Noise as Factor in Hearing Disorders

2019 ◽  
Vol 105 (6) ◽  
pp. 904-911 ◽  
Author(s):  
Ewa Skrodzka ◽  
Andrzej Wicher ◽  
Roman Gołe¸biewski
Keyword(s):  
Hearing Loss ◽  
Hair Cells ◽  
Impulse Noise ◽  
Noise Exposure ◽  
Single Shot ◽  
Negative Consequences ◽  
Mean Values ◽  
Sport Training ◽  
Wide Range ◽  
Auditory Systems

The impulse noise produced by personal weapons (guns, rifles, shotguns) during military activity, and while people engage in sport, training and hunting, is a threat to the auditory systems of soldiers, civilians, policemen, hunters, forest officers, sportspeople and bystanders not actively engaged in professional or recreational firing. An overview of noise levels generated by different types of weapon is provided, and potential short-term and long-term consequences for the human auditory system are described. The mean values of LC, peak sound pressure level during the shot, at the shooter's ears, for various types of weapons are approximately 160 dB SPL. These are levels that can cause permanent, irreversible negative effects on hearing (hearing loss, tinnitus, etc.) even as a result of a single shot being fired. One of the largest groups of weapon users in Poland (about 120 thousand) are hunters and field masters. They are not obligated by any regulations to protect their auditory systems from impulse noise. This means that this group of firearm users is at particularly high risk of hearing damage. On the basis of the literature review, it is shown that hearing exposure to high-level impulse noise such as a gunshot can result in such consequences as damage to the middle ear and destruction of the outer/inner hair cells in the cochlea. Especially difficult to diagnose is 'hidden hearing loss', i.e. damage to the synaptic connections between the hair cells of the inner ear and the auditory nerve fibres, which is not reflected in the results of basic audiometric testing and can cause hearing problems many years after impulse noise exposure. The wide range of negative consequences of gunfire noise clearly indicates the need for the hearing of the shooters to be protected.

scholarly journals miR-153/KCNQ4 axis contributes to noise-induced hearing loss in a mouse model

2021 ◽  
Vol 71 (1) ◽  
Author(s):  
Qin Wang ◽  
Wei Li ◽  
Cuiyun Cai ◽  
Peng Hu ◽  
Ruosha Lai
Keyword(s):  
Hearing Loss ◽  
Hair Cells ◽  
Noise Exposure ◽  
Auditory Brainstem ◽  
Sensory Epithelium ◽  
Outer Hair Cells ◽  
Broadband Noise ◽  
Hek293 Cells ◽  
Auditory Brainstem Responses ◽  
Luciferase Reporter

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.

scholarly journals Treatment With Calcineurin Inhibitor FK506 Attenuates Noise-Induced Hearing Loss

2021 ◽  
Vol 9 ◽  
Author(s):  
Zu-Hong He ◽  
Song Pan ◽  
Hong-Wei Zheng ◽  
Qiao-Jun Fang ◽  
Kayla Hill ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hair Cells ◽  
Calcineurin Inhibitor ◽  
Noise Exposure ◽  
Cell Loss ◽  
Outer Hair Cells ◽  
Oxygen Species ◽  
Noise Induced Hearing Loss ◽  
Activated T Cells ◽  
Interfering Rna

Attenuation of noise-induced hair cell loss and noise-induced hearing loss (NIHL) by treatment with FK506 (tacrolimus), a calcineurin (CaN/PP2B) inhibitor used clinically as an immunosuppressant, has been previously reported, but the downstream mechanisms of FK506-attenuated NIHL remain unknown. Here we showed that CaN immunolabeling in outer hair cells (OHCs) and nuclear factor of activated T-cells isoform c4 (NFATc4/NFAT3) in OHC nuclei are significantly increased after moderate noise exposure in adult CBA/J mice. Consequently, treatment with FK506 significantly reduces moderate-noise-induced loss of OHCs and NIHL. Furthermore, induction of reactive oxygen species (ROS) by moderate noise was significantly diminished by treatment with FK506. In agreement with our previous finding that autophagy marker microtubule-associated protein light chain 3B (LC3B) does not change in OHCs under conditions of moderate-noise-induced permanent threshold shifts, treatment with FK506 increases LC3B immunolabeling in OHCs after exposure to moderate noise. Additionally, prevention of NIHL by treatment with FK506 was partially abolished by pretreatment with LC3B small interfering RNA. Taken together, these results indicate that attenuation of moderate-noise-induced OHC loss and hearing loss by FK506 treatment occurs not only via inhibition of CaN activity but also through inhibition of ROS and activation of autophagy.

scholarly journals The Physiological Bases of Hidden Noise-Induced Hearing Loss: Protocol for a Functional Neuroimaging Study (Preprint)

2017 ◽  
Author(s):  
Rebecca Susan Dewey ◽  
Deborah A Hall ◽  
Hannah Guest ◽  
Garreth Prendergast ◽  
Christopher J Plack ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Noise Exposure ◽  
Functional Neuroimaging ◽  
Nerve Fibers ◽  
High Threshold ◽  
Hearing Level ◽  
Noise Induced Hearing Loss ◽  
Brainstem Response ◽  
Neuroimaging Study ◽  
Hidden Hearing Loss

BACKGROUND Rodent studies indicate that noise exposure can cause permanent damage to synapses between inner hair cells and high-threshold auditory nerve fibers, without permanently altering threshold sensitivity. These demonstrations of what is commonly known as hidden hearing loss have been confirmed in several rodent species, but the implications for human hearing are unclear. OBJECTIVE Our Medical Research Council–funded program aims to address this unanswered question, by investigating functional consequences of the damage to the human peripheral and central auditory nervous system that results from cumulative lifetime noise exposure. Behavioral and neuroimaging techniques are being used in a series of parallel studies aimed at detecting hidden hearing loss in humans. The planned neuroimaging study aims to (1) identify central auditory biomarkers associated with hidden hearing loss; (2) investigate whether there are any additive contributions from tinnitus or diminished sound tolerance, which are often comorbid with hearing problems; and (3) explore the relation between subcortical functional magnetic resonance imaging (fMRI) measures and the auditory brainstem response (ABR). METHODS Individuals aged 25 to 40 years with pure tone hearing thresholds ≤20 dB hearing level over the range 500 Hz to 8 kHz and no contraindications for MRI or signs of ear disease will be recruited into the study. Lifetime noise exposure will be estimated using an in-depth structured interview. Auditory responses throughout the central auditory system will be recorded using ABR and fMRI. Analyses will focus predominantly on correlations between lifetime noise exposure and auditory response characteristics. RESULTS This paper reports the study protocol. The funding was awarded in July 2013. Enrollment for the study described in this protocol commenced in February 2017 and was completed in December 2017. Results are expected in 2018. CONCLUSIONS This challenging and comprehensive study will have the potential to impact diagnostic procedures for hidden hearing loss, enabling early identification of noise-induced auditory damage via the detection of changes in central auditory processing. Consequently, this will generate the opportunity to give personalized advice regarding provision of ear defense and monitoring of further damage, thus reducing the incidence of noise-induced hearing loss.

scholarly journals Outcomes of Peptide Vaccine GV1001 Treatment in a Murine Model of Acute Noise-Induced Hearing Loss

Antioxidants ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 112
Author(s):  
Sang-Yeon Lee ◽  
Jae Joon Han ◽  
Sang-Youp Lee ◽  
Gaon Jung ◽  
Hyun Jin Min ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
White Noise ◽  
Hair Cells ◽  
Murine Model ◽  
Outer Hair Cells ◽  
Saline Control ◽  
Noise Induced Hearing Loss ◽  
Cochlear Hair Cells ◽  
Ribbon Synapses

Noise-induced hearing loss (NIHL) is primarily caused by damage to cochlear hair cells, associated with synaptopathy. The novel cell-penetrating peptide GV1001, an antitumor agent, also has antioxidant and anti-inflammatory effects, and is otoprotective in a murine model of kanamycin-induced ototoxicity. Here, we explored whether GV1001 attenuated NIHL, and the underlying mechanism at play. We established an NIHL model by exposing 4- to 6-week-old C57/BL6 mice to white noise at 120 dB SPL for 2 h, resulting in a significant permanent threshold shift (PTS). We then subcutaneously injected saline (control), GV1001, or dexamethasone immediately after cessation of PTS-noise exposure and evaluated the threshold shifts, structural damages to outer hair cells (OHCs), and ribbon synapses. We also verified whether GV1001 attenuates oxidative stress at the level of lipid peroxidation or protein nitration in OHCs 1 h after exposure to white noise at 120 dB SPL. GV1001-treated mice exhibited significantly less hearing threshold shifts over 2 weeks and preserved OHCs and ribbon synapses compared with controls. Similarly, dexamethasone-treated mice showed comparable protection against NIHL. Importantly, GV1001 markedly attenuated oxidative stress in OHCs. Our findings suggest that GV1001 may protect against NIHL by lowering oxidative stress and may serve as preventive or adjuvant treatment.

scholarly journals Cochlear Synaptopathy and Noise-Induced Hidden Hearing Loss

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Lijuan Shi ◽  
Ying Chang ◽  
Xiaowei Li ◽  
Steve Aiken ◽  
Lijie Liu ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Noise Exposure ◽  
Human Subjects ◽  
Spiral Ganglion ◽  
Nerve Fibers ◽  
Type I ◽  
Functional Deficits ◽  
Ganglion Neurons ◽  
Hidden Hearing Loss ◽  
Signal Coding

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.

scholarly journals Inhibition of Cochlear HMGB1 Expression Attenuates Oxidative Stress and Inflammation in an Experimental Murine Model of Noise-Induced Hearing Loss

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 810
Author(s):  
Cheng-Ping Shih ◽  
Chao-Yin Kuo ◽  
Yuan-Yung Lin ◽  
Yi-Chun Lin ◽  
Hang-Kang Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Noise Exposure ◽  
Outer Hair Cells ◽  
Control Group ◽  
Noise Induced Hearing Loss ◽  
Post Exposure ◽  
Nadph Oxidase 4 ◽  
Brainstem Response ◽  
Ros Formation

Noise-induced hearing loss (NIHL) is a common inner ear disease but has complex pathological mechanisms, one of which is increased oxidative stress in the cochlea. The high-mobility group box 1 (HMGB1) protein acts as an inflammatory mediator and shows different activities with redox modifications linked to the generation of reactive oxygen species (ROS). We aimed to investigate whether manipulation of cochlear HMGB1 during noise exposure could prevent noise-induced oxidative stress and hearing loss. Sixty CBA/CaJ mice were divided into two groups. An intraperitoneal injection of anti-HMGB1 antibodies was administered to the experimental group; the control group was injected with saline. Thirty minutes later, all mice were subjected to white noise exposure. Subsequent cochlear damage, including auditory threshold shifts, hair cell loss, expression of cochlear HMGB1, and free radical activity, was then evaluated. The levels of HMGB1 and 4-hydroxynonenal (4-HNE), as respective markers of reactive nitrogen species (RNS) and ROS formation, showed slight increases on post-exposure day 1 and achieved their highest levels on post-exposure day 4. After noise exposure, the antibody-treated mice showed markedly less ROS formation and lower expression of NADPH oxidase 4 (NOX4), nitrotyrosine, inducible nitric oxide synthase (iNOS), and intercellular adhesion molecule-1 (ICAM‑1) than the saline-treated control mice. A significant amelioration was also observed in the threshold shifts of the auditory brainstem response and the loss of outer hair cells in the antibody-treated versus the saline-treated mice. Our results suggest that inhibition of HMGB1 by neutralization with anti-HMGB1 antibodies prior to noise exposure effectively attenuated oxidative stress and subsequent inflammation. This procedure could therefore have potential as a therapy for NIHL.

scholarly journals Primed to Die: An Investigation of the Genetic Mechanisms Underlying Noise-Induced Hearing Loss and Cochlear Damage in Homozygous Foxo3-knockout Mice

2021 ◽  
Author(s):  
Holly J. Beaulac ◽  
Felicia Gilels ◽  
Jingyuan Zhang ◽  
Sarah Jeoung ◽  
Patricia M. White
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Noise Exposure ◽  
Multiphoton Microscopy ◽  
Cell Loss ◽  
Outer Hair Cells ◽  
Noise Induced Hearing Loss ◽  
Knock Out ◽  
Cell Death Pathway ◽  
Cochlear Damage

AbstractThe prevalence of noise-induced hearing loss (NIHL) continues to increase, with limited therapies available for individuals with cochlear damage. We have previously established that the transcription factor FOXO3 is necessary to preserve outer hair cells (OHCs) and hearing thresholds up to two weeks following a mild noise exposure in mice. The mechanisms by which FOXO3 preserves cochlear cells and function are unknown. In this study, we analyzed the immediate effects of mild noise exposure on wild-type, Foxo3 heterozygous (Foxo3+/KO), and Foxo3 knock-out (Foxo3KO/KO) mice to better understand FOXO3’s role(s) in the mammalian cochlea. We used confocal and multiphoton microscopy to examine well-characterized components of noise-induced damage including calcium regulators, oxidative stress, necrosis, and caspase-dependent and -independent apoptosis. Lower immunoreactivity of the calcium buffer oncomodulin in Foxo3KO/KO OHCs correlated with cell loss beginning 4 hours post-noise exposure. Using immunohistochemistry, we identified parthanatos as the cell death pathway for OHCs. Oxidative stress response pathways were not significantly altered in FOXO3’s absence. We used RNA sequencing to identify and RT-qPCR to confirm differentially expressed genes. We further investigated a gene downregulated in the unexposed Foxo3KO/KO mice that may contribute to OHC noise susceptibility. Glycerophosphodiester Phosphodiesterase Domain Containing 3 (GDPD3), a possible endogenous source of lysophosphatidic acid (LPA), has not previously been described in the cochlea. As LPA reduces OHC loss after severe noise exposure, we treated noise exposed Foxo3KO/KO mice with exogenous LPA. LPA treatment delayed immediate damage to OHCs but was insufficient to ultimately prevent their death or prevent hearing loss. These results suggest that FOXO3 acts prior to acoustic insult to maintain cochlear resilience, possibly through sustaining endogenous LPA levels.

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