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Journal of Otolaryngology - Head & Neck... Dec 2023Noise exposure is an important cause of acquired hearing loss. Studies have found that noise exposure causes dysregulated redox homeostasis in cochlear tissue, which has... (Review)
Review
Noise exposure is an important cause of acquired hearing loss. Studies have found that noise exposure causes dysregulated redox homeostasis in cochlear tissue, which has been recognized as a signature feature of hearing loss. Oxidative stress plays a pivotal role in many diseases via very complex and diverse mechanisms and targets. Reactive oxygen species are products of oxidative stress that exert toxic effects on a variety of physiological activities and are considered significant in noise-induced hearing loss (NIHL). Endogenous cellular antioxidants can directly or indirectly counteract oxidative stress and regulate intracellular redox homeostasis, and exogenous antioxidants can complement and enhance this effect. Therefore, antioxidant therapy is considered a promising direction for NIHL treatment. However, drug experiments have been limited to animal models of NIHL, and these experiments and related observations are difficult to translate in humans; therefore, the mechanisms and true effects of these drugs need to be further analyzed. This review outlines the effects of oxidative stress in NIHL and discusses the main mechanisms and strategies of antioxidant treatment for NIHL.
Topics: Animals; Humans; Hearing Loss, Noise-Induced; Antioxidants; Oxidative Stress; Oxidation-Reduction; Homeostasis
PubMed: 38082455
DOI: 10.1186/s40463-023-00686-x -
Journal of Speech, Language, and... Dec 2023The purpose of this study is to critically evaluate lifetime noise exposure history (LNEH) reporting. First, two different approaches to evaluate the cumulative LNEH...
PURPOSE
The purpose of this study is to critically evaluate lifetime noise exposure history (LNEH) reporting. First, two different approaches to evaluate the cumulative LNEH were compared. Second, individual LNEH was associated with the subjects' hearing status. Third, loudness estimates of exposure activities, by means of Jokitulppo- and Ferguson-based exposure levels, were compared with dosimeter sound-level measurements.
METHOD
One hundred one young adults completed the questionnaires, and a subgroup of 30 subjects underwent audiological assessment. Pure-tone audiometry, speech-in-noise intelligibility, distortion product otoacoustic emissions, auditory brainstem responses, and envelope following responses were included. Fifteen out of the 30 subjects took part in a noisy activity while wearing a dosimeter.
RESULTS
First, results demonstrate that the structured questionnaire yielded a greater amount of information pertaining to the diverse activities, surpassing the insights obtained from an open-ended questionnaire. Second, no significant correlations between audiological assessment and LNEH were found. Lastly, the results indicate that Ferguson-based exposure levels offer a more precise estimation of the actual exposure levels, in contrast to Jokitulppo-based estimates.
CONCLUSIONS
We propose several recommendations for determining the LNEH. First, it is vital to define accurate loudness categories and corresponding allocated levels, with a preference for the loudness levels proposed by Ferguson et al. (2019), as identified in this study. Second, a structured questionnaire regarding LNEH is recommended, discouraging open-ended questioning. Third, it is essential to include a separate category exclusively addressing work-related activities, encompassing various activities for more accurate surveying.
Topics: Young Adult; Humans; Otoacoustic Emissions, Spontaneous; Auditory Threshold; Noise; Audiometry, Pure-Tone; Hearing Loss, Noise-Induced
PubMed: 37988687
DOI: 10.1044/2023_JSLHR-23-00266 -
International Journal of Audiology Apr 2024
Topics: Humans; Hearing Loss, Noise-Induced
PubMed: 37029688
DOI: 10.1080/14992027.2023.2197147 -
Brain, Behavior, and Immunity Nov 2023Acquired peripheral hearing loss (APHL) in midlife has been identified as the greatest modifiable risk factor for dementia; however, the pathophysiological neural...
Voluntary wheel exercise ameliorates cognitive impairment, hippocampal neurodegeneration and microglial abnormalities preceded by demyelination in a male mouse model of noise-induced hearing loss.
Acquired peripheral hearing loss (APHL) in midlife has been identified as the greatest modifiable risk factor for dementia; however, the pathophysiological neural mechanisms linking APHL with an increased risk of dementia remain to be elucidated. Here, in an adult male mouse model of noise-induced hearing loss (NIHL), one of the most common forms of APHL, we demonstrated accelerated age-related cognitive decline and hippocampal neurodegeneration during a 6-month follow-up period, accompanied by progressive hippocampal microglial aberrations preceded by immediate-onset transient elevation in serum glucocorticoids and delayed-onset sustained myelin disruption in the hippocampus. Pretreatment with the glucocorticoid receptor antagonist RU486 before stressful noise exposure partially mitigated the early activation of hippocampal microglia, which were present at 7 days post noise exposure (7DPN), but had no impact on later microglial aberrations, hippocampal neurodegeneration, or cognitive decline exhibited at 1 month post noise exposure (1MPN). One month of voluntary wheel exercise following noise exposure barely affected either the hearing threshold shift or hippocampal myelin changes but effectively countered cognitive impairment and the decline in hippocampal neurogenesis in NIHL mice at 1MPN, paralleled by the normalization of microglial morphology, which coincided with a reduction in microglial myelin inclusions and a restoration of microglial hypoxia-inducible factor-1α (HIF1α) expression. Our results indicated that accelerated cognitive deterioration and hippocampal neuroplastic decline following NIHL are most likely driven by the maladaptive response of hippocampal microglia to myelin damage secondary to hearing loss, and we also demonstrated the potential of voluntary physical exercise as a promising and cost-effective strategy to alleviate the detrimental impact of APHL on cognitive function and thus curtail the high and continuously increasing global burden of dementia. Furthermore, the findings of the present study highlight the contribution of myelin debris overload to microglial malfunction and identify the microglial HIF1α-related pathway as an attractive candidate for future comprehensive investigation to obtain a more definitive picture of the underlying mechanisms linking APHL and dementia.
PubMed: 37683962
DOI: 10.1016/j.bbi.2023.09.002 -
Antioxidants & Redox Signaling Mar 2024The stria vascularis, located in the inner ear, consists of three layers, one of which is the blood-labyrinth barrier (BLB). It is formed by endothelial cells, sealed... (Review)
Review
The stria vascularis, located in the inner ear, consists of three layers, one of which is the blood-labyrinth barrier (BLB). It is formed by endothelial cells, sealed together to prevent the passage of toxic substances from the blood to the inner ear, by pericytes and perivascular-resident macrophage-like melanocyte. There are various causes that lead to hearing loss, and among these are noise-induced and autoimmune hearing loss, ear disorders related to ototoxic medication, Ménière's disease, and age-related hearing loss. For all of these, major therapeutic interventions include drug-loaded nanoparticles, intratympanic or intracochlear delivery. Since many pathologies associated with hearing loss are characterized by a weakening of the BLB, in this review, the molecular mechanisms underlying the response to damage of BLB cellular components have been discussed. In addition, insight into the role of hormetic nutrients against hearing loss pathology is proposed. BLB cellular components of neurovascular cochlear unit play important physiological roles, owing to their impermeable function against all ototoxic substances that can induce damage. Studies are needed to investigate the cross talk occurring between these cellular components to exploit their possible role as novel targets for therapeutic interventions that may unravel future path based on the use of hormetic nutrients. 40, 542-563.
Topics: Humans; Endothelial Cells; Ear, Inner; Cochlea; Hearing Loss; Pericytes
PubMed: 37565276
DOI: 10.1089/ars.2023.0251 -
Biomedicine & Pharmacotherapy =... Oct 2023Over-production of reactive oxygen species (ROS) in the inner ear can be triggered by a variety of pathological events identified in animal models after traumatic noise...
Over-production of reactive oxygen species (ROS) in the inner ear can be triggered by a variety of pathological events identified in animal models after traumatic noise exposure. Our previous research found that inhibition of the AMP-activated protein kinase alpha subunit (AMPKα) protects against noise-induced cochlear hair cell loss and hearing loss by reducing ROS accumulation. However, the molecular pathway through which AMPKα exerts its antioxidative effect is still unclear. In this study, we have investigated a potential target of AMPKα and ROS, cystic fibrosis transmembrane conductance regulator (CFTR), and the protective effect against noise-induced hair cell loss of an FDA-approved CFTR potentiator, ivacaftor, in FVB/NJ mice, mouse explant cultures, and HEI-OC1 cells. We found that noise exposure increases phosphorylation of CFTR at serine 737 (p-CFTR, S737), which reduces wildtype CFTR function, resulting in oxidative stress in cochlear sensory hair cells. Pretreatment with a single dose of ivacaftor maintains CFTR function by preventing noise-increased p-CFTR (S737). Furthermore, ivacaftor treatment increases nuclear factor E2-related factor 2 (Nrf2) expression, diminishes ROS formation, and attenuates noise-induced hair cell loss and hearing loss. Additionally, inhibition of noise-induced AMPKα activation by compound C also diminishes p-CFTR (S737) expression. In line with these in-vivo results, administration of hydrogen peroxide to cochlear explants or HEI-OC1 cells increases p-CFTR (S737) expression and induces sensory hair cell or HEI-OC1 cell damage, while application of ivacaftor halts these effects. Although ivacaftor increases Nrf2 expression and reduces ROS accumulation, cotreatment with ML385, an Nrf2 inhibitor, abolishes the protective effects of ivacaftor against hydrogen-peroxide-induced HEI-OC1 cell death. Our results indicate that noise-induced sensory hair cell damage is associated with p-CFTR. Ivacaftor has potential for treatment of noise-induced hearing loss by maintaining CFTR function and increasing Nrf2 expression for support of redox homeostasis in sensory hair cells.
Topics: Animals; Mice; NF-E2-Related Factor 2; Reactive Oxygen Species; Cystic Fibrosis Transmembrane Conductance Regulator; Oxidative Stress; Hair Cells, Auditory; AMP-Activated Protein Kinases; Alopecia; Antibodies; Oxidation-Reduction
PubMed: 37657258
DOI: 10.1016/j.biopha.2023.115399 -
Frontiers in Pediatrics 2023An increasingly 24/7 connected and urbanised world has created a silent pandemic of noise-induced hearing loss. Ensuring survival to children born (extremely) preterm is...
BACKGROUND
An increasingly 24/7 connected and urbanised world has created a silent pandemic of noise-induced hearing loss. Ensuring survival to children born (extremely) preterm is crucial. The incubator is a closed medical device, modifying the internal climate, and thus providing an environment for the child, as safe, warm, and comfortable as possible. While sound outside the incubator is managed and has decreased over the years, managing the noise inside the incubator is still a challenge.
METHOD
Using active noise cancelling in an incubator will eliminate unwanted sounds (i.e., from the respirator and heating) inside the incubator, and by adding sophisticated algorithms, normal human speech, neonatal intensive care unit music-based therapeutic interventions, and natural sounds will be sustained for the child in the pod. Applying different methods such as active noise cancelling, motion capture, sonological engineering. and sophisticated machine learning algorithms will be implemented in the development of the incubator.
PROJECTED RESULTS
A controlled and active sound environment in and around the incubator can in turn promote the wellbeing, neural development, and speech development of the child and minimise distress caused by unwanted noises. While developing the hardware and software pose individual challenges, it is about the system design and aspects contributing to it. On the one hand, it is crucial to measure the auditory range and frequencies in the incubator, as well as the predictable sounds that will have to be played back into the environment. On the other, there are many technical issues that have to be addressed when it comes to algorithms, datasets, delay, microphone technology, transducers, convergence, tracking, impulse control and noise rejection, noise mitigation stability, detection, polarity, and performance.
CONCLUSION
Solving a complex problem like this, however, requires a de-disciplinary approach, where each discipline will realise its own shortcomings and boundaries, and in turn will allow for innovations and new avenues. Technical developments used for building the active noise cancellation-incubator have the potential to contribute to improved care solutions for patients, both infants and adults.Code available at: 10.3389/fped.2023.1187815.
PubMed: 37465419
DOI: 10.3389/fped.2023.1187815 -
Advanced Science (Weinheim,... Jan 2024Noise-induced hearing loss (NIHL) is a common outcome of excessive reactive oxygen species in the cochlea, and the targeted delivery of antioxidants to the inner ear is...
Noise-induced hearing loss (NIHL) is a common outcome of excessive reactive oxygen species in the cochlea, and the targeted delivery of antioxidants to the inner ear is a potential therapeutic strategy. In this paper, a novel natural biomaterials-derived multifunctional delivery system using silk fibroin-polydopamine (PDA)-composited inverse opal microcarriers (PDA@SFMCs) is presented for inner ear drug delivery and NIHL therapy. Due to their large specific surface area and interpenetrating nanochannels, PDA@SFMCs can rapidly load active biomolecules making them a convenient medium for the storage and delivery of such molecules. In addition, surface modification of PDA enables the microcarriers to remain in the round window niche, thus facilitating the precise local and directed delivery of loaded drugs. Based on these features, it is demonstrated here that n-acetylcysteine-loaded silk microcarriers have satisfactory antioxidant properties on cells and can successfully prevent NIHL in guinea pigs. These results indicate that the natural multifunctional silk microcarriers are promising agents for local inner ear drug delivery in the clinic.
Topics: Animals; Guinea Pigs; Hearing Loss, Noise-Induced; Silk; Ear, Inner; Cochlea; Drug Delivery Systems; Antioxidants
PubMed: 37984871
DOI: 10.1002/advs.202305215 -
National Science Review Jun 2024Noise-induced hearing loss (NIHL) is a highly prevalent form of sensorineural hearing damage that has significant negative effects on individuals of all ages and there...
Noise-induced hearing loss (NIHL) is a highly prevalent form of sensorineural hearing damage that has significant negative effects on individuals of all ages and there are no effective drugs approved by the US Food and Drug Administration. In this study, we unveil the potential of superparamagnetic iron oxide nanoparticle assembly (SPIOCA) to reshape the dysbiosis of gut microbiota for treating NIHL. This modulation inhibits intestinal inflammation and oxidative stress responses, protecting the integrity of the intestinal barrier. Consequently, it reduces the transportation of pathogens and inflammatory factors from the bloodstream to the cochlea. Additionally, gut microbiota-modulated SPIOCA-induced metabolic reprogramming in the gut-inner ear axis mainly depends on the regulation of the sphingolipid metabolic pathway, which further contributes to the restoration of hearing function. Our study confirms the role of the microbiota-gut-inner ear axis in NIHL and provides a novel alternative for the treatment of NIHL and other microbiota dysbiosis-related diseases.
PubMed: 38707203
DOI: 10.1093/nsr/nwae100 -
Proceedings of the National Academy of... Feb 2024Exposure to loud noise triggers sensory organ damage and degeneration that, in turn, leads to hearing loss. Despite the troublesome impact of noise-induced hearing loss...
Exposure to loud noise triggers sensory organ damage and degeneration that, in turn, leads to hearing loss. Despite the troublesome impact of noise-induced hearing loss (NIHL) in individuals and societies, treatment strategies that protect and restore hearing are few and insufficient. As such, identification and mechanistic understanding of the signaling pathways involved in NIHL are required. Biological zinc is mostly bound to proteins, where it plays major structural or catalytic roles; however, there is also a pool of unbound, mobile (labile) zinc. Labile zinc is mostly found in vesicles in secretory tissues, where it is released and plays a critical signaling role. In the brain, labile zinc fine-tunes neurotransmission and sensory processing. However, injury-induced dysregulation of labile zinc signaling contributes to neurodegeneration. Here, we tested whether zinc dysregulation occurs and contributes to NIHL in mice. We found that ZnT3, the vesicular zinc transporter responsible for loading zinc into vesicles, is expressed in cochlear hair cells and the spiral limbus, with labile zinc also present in the same areas. Soon after noise trauma, ZnT3 and zinc levels are significantly increased, and their subcellular localization is vastly altered. Disruption of zinc signaling, either via ZnT3 deletion or pharmacological zinc chelation, mitigated NIHL, as evidenced by enhanced auditory brainstem responses, distortion product otoacoustic emissions, and number of hair cell synapses. These data reveal that noise-induced zinc dysregulation is associated with cochlear dysfunction and recovery after NIHL, and point to zinc chelation as a potential treatment for mitigating NIHL.
Topics: Mice; Animals; Hearing Loss, Noise-Induced; Zinc; Cochlea; Noise; Hearing; Evoked Potentials, Auditory, Brain Stem; Auditory Threshold
PubMed: 38354264
DOI: 10.1073/pnas.2310561121