scholarly journals Nondeterministic nature of sensorineural outcomes following noise trauma

Biology Open ◽  
2021 ◽  
Vol 10 (10) ◽  
Author(s):  
O'neil W. Guthrie ◽  
Ishan S. Bhatt
Keyword(s):  
Hearing Loss ◽  
Noise Exposure ◽  
Outer Hair Cells ◽  
Male Rats ◽  
Noise Induced Hearing Loss ◽  
Cochlear Function ◽  
History Of Research ◽  
History Of ◽  
And Control ◽  
The Relationship

ABSTRACT Over 1.1 billion individuals are at risk for noise induced hearing loss yet there is no accepted therapy. A long history of research has demonstrated that excessive noise exposure will kill outer hair cells (OHCs). Such observations have fueled the notion that dead OHCs underlie hearing loss. Therefore, previous and current therapeutic approaches are based on preventing the loss of OHCs. However, the relationship between OHC loss and hearing loss is at best a modest correlation. This suggests that in addition to the death of OHCs, other mechanisms may regulate the type and degree of hearing loss. In the current study, we tested the hypothesis that permanent noise-induced-hearing loss is consequent to additional mechanisms beyond the noise dose and the death of OHCs. Hooded male rats were randomly divided into noise and control groups. Morphological and physiological assessments were conducted on both groups. The combined results suggest that beyond OHC loss, the surviving cochlear elements shape sensorineural outcomes, which can be nondeterministic. These findings provide the basis for individualized ototherapeutics that manipulate surviving cellular elements in order to bias cochlear function towards normal hearing even in the presence of dead OHCs.

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.

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 Relationship between CDH23 gene and risk of noise-induced hearing loss

2021 ◽  
Author(s):  
Jie Jiao ◽  
Shanfa Yu ◽  
Guizhen Gu ◽  
Guoshun Chen ◽  
Huanling Zhang ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Noise Exposure ◽  
Control Group ◽  
Case Group ◽  
Noise Induced Hearing Loss ◽  
Nucleotide Polymorphisms ◽  
Significant Relationships ◽  
Increased Risk ◽  
Main Effects ◽  
The Relationship

Abstract Objective: To investigate the relationship between CDH23 gene and the risk of noise-induced hearing loss (NIHL).Methods: This was a case-control study. Noise-exposed workers worked in a steel factory in North China was recruited and been divided into two groups: the case group (BHFTA ≥40 dB) and the control group (BHFTA<25 dB). We analyzed the association among 18 single nucleotide polymorphisms (SNPs) in CDH23 and NIHL risk using the generalized multifactor dimensionality reduction (GMDR) method. Logistic regression was performed to analyze the main effects of SNPs and the interactions between CNE and SNPs adjusting cumulative noise exposure (CNE), smoking, drinking, physical exercise and hypertension. Results: In this study, 776 subjects of period I and 1117 subjects of period I+II were recruited. The results showed that subjects who carried the AA genotype of rs3802711possessed significantly increased risk of NIHL than those carrying GG (OR: 2.71; 95% CI:1.15, 6.39) and GA+GG (OR: 2.54; 95% CI: 1.09, 6.00) in period I, respectively. For rs11592462, subjects carrying the GG genotype showed a significantly increased risk of NIHL compared with the subjects. Significant relationships were showed between rs10999947, rs3802711, rs10762480, rs3752751, rs3752752, rs3747867, and rs11592462 for NIHL overall and various CNE strata. There was no significant association between the rs1227049 - rs3752752 - rs10999947 - rs3752751 - rs10762480 - rs3802711 - rs11592462 - rs4747195 - rs4747194 - rs10466026 haplotypes and NIHL risk. Conclusions: The genetic variation in the CDH23 gene might play an important role in determining individual susceptibility to NIHL.

scholarly journals Association of Dietary Factors with Noise Induced Hearing Loss in Korean Population: A 3-Year National Cohort Study

2021 ◽  
Author(s):  
Hyun Jin Lee ◽  
Juhyung Lee ◽  
Chulyoung Yoon ◽  
Yesai Park ◽  
Young-Hoon Joo ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Marital Status ◽  
Noise Exposure ◽  
Smoking Status ◽  
Dietary Factors ◽  
Noise Induced Hearing Loss ◽  
Health And Nutrition ◽  
National Cohort ◽  
Using Data ◽  
The Relationship

Abstract Noise-induced hearing loss (NIHL) is a hearing impairment caused by various epidemiologic and clinical factors. Identifying the relationship between NIHL and nutrients could help reduce the prevalence of hearing loss. This study analyzed the relationship between NIHL and dietary factors using data of the Korea National Health and Nutrition Examination survey. The survey was taken by a total of 10,850 participants aged 20-65 years. Air conduction audiometry was measured at 500, 1000, 2000, and 4000Hz in both ears. Metabolic syndrome, noise exposure, drink, smoke, income, marital status, and nutritional intake were evaluated. The differences between non-HI and HI participants in noise-exposed group have shown statistically significant differences in age, sex, marital status, smoking status, alcohol consumption, fast glucose level, and triglyceride level (p<0.05). In a multiple regression analysis, the age factor showed a significant association with HI (OR: 0.604; 95% CI: 0.538-0.678). In multivariate analysis for dietary factors, Retinol (OR: 1.356; 95% CI: 1.068-1.722), Niacin (OR: 1.5; 95% CI: 1.022-2.201) and Carbohydrates (OR: 0.692; 95% CI: 0.486-0.985) showed a significant association with NIHL. When the dietary factors of the noise exposure group were analyzed, high intake of Niacin and Retinol and low intake of Carbohydrates appear to prevent hearing loss.

scholarly journals Constant Light Dysregulates Cochlear Circadian Clock and Exacerbates Noise-Induced Hearing Loss

2020 ◽  
Vol 21 (20) ◽  
pp. 7535
Author(s):  
Chao-Hui Yang ◽  
Chung-Feng Hwang ◽  
Jiin-Haur Chuang ◽  
Wei-Shiung Lian ◽  
Feng-Sheng Wang ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Circadian Clock ◽  
Auditory System ◽  
High Intensity ◽  
Noise Exposure ◽  
Clock Genes ◽  
Outer Hair Cells ◽  
Constant Light ◽  
Noise Induced Hearing Loss ◽  
Brainstem Response

Noise-induced hearing loss is one of the major causes of acquired sensorineural hearing loss in modern society. While people with excessive exposure to noise are frequently the population with a lifestyle of irregular circadian rhythms, the effects of circadian dysregulation on the auditory system are still little known. Here, we disturbed the circadian clock in the cochlea of male CBA/CaJ mice by constant light (LL) or constant dark. LL significantly repressed circadian rhythmicity of circadian clock genes Per1, Per2, Rev-erbα, Bmal1, and Clock in the cochlea, whereas the auditory brainstem response thresholds were unaffected. After exposure to low-intensity (92 dB) noise, mice under LL condition initially showed similar temporary threshold shifts to mice under normal light–dark cycle, and mice under both conditions returned to normal thresholds after 3 weeks. However, LL augmented high-intensity (106 dB) noise-induced permanent threshold shifts, particularly at 32 kHz. The loss of outer hair cells (OHCs) and the reduction of synaptic ribbons were also higher in mice under LL after noise exposure. Additionally, LL enhanced high-intensity noise-induced 4-hydroxynonenal in the OHCs. Our findings convey new insight into the deleterious effect of an irregular biological clock on the auditory system.

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 A retrospective study of noise induced hearing loss in a tertiary care hospital of Jharkhand - an alarming but ignorant truth

2017 ◽  
Vol 3 (2) ◽  
pp. 340
Author(s):  
Pradeep Kumar Singh ◽  
Nishant Kumar ◽  
Dheeraj Kumar ◽  
Nisha Shrivastava ◽  
Abhishek Kumar
Keyword(s):  
Hearing Loss ◽  
Noise Exposure ◽  
Tertiary Care ◽  
Total Sample ◽  
Care Hospital ◽  
Age Group ◽  
Noise Induced Hearing Loss ◽  
Medical Sciences ◽  
Urban Males ◽  
History Of

<p class="abstract"><strong>Background:</strong> Noise induced hearing loss (NIHL) is hearing impairment resulting from exposure to loud sound. People may have a loss of perception of a narrow range of frequencies, impaired cognitive perception of sound, or other impairment, including sensitivity to sound or ringing in the ears. NIHL is 2<sup>nd</sup> most common cause of hearing loss, next to presbycusis. Most of the population of developing countries is ignorant of the hazards of excessive noise exposure. 1) To describe the socio-demograpic profile of patients in the young age group (18-35 years) with noise induced hearing loss in Rajendra Institute of Medical Sciences (RIMS), Ranchi during June 2015- November 2016. 2) To study the major presenting complaints. 3) To categorize the patients on the basis of degree of hearing loss.</p><p class="abstract"><strong>Methods:</strong> Data for study was collected from RIMS Out Patient Department (OPD) register during period June 2015 – November 2016 (18 months).Total sample size for this period was 50. Templates were generated in MS excel sheet and data analysis was done using SPSS software (version 20).  </p><p class="abstract"><strong>Results:</strong> Study showed NIHL was more common in urban (82%) and male (72%) population. More than half (54%) patients presented with hearing loss and 24% with tinnitus. Most of the patients had bilateral mild hearing loss (70%).</p><p><strong>Conclusions:</strong> NIHL is more common in urban males, mostly in age group (26-35 years). More than 2/3<sup>rd</sup> (68% ) of patients had history of exposure to loud noise. </p>

scholarly journals Audiometric Phenotypes of Noise-Induced Hearing Loss by Data-Driven Cluster Analysis and Their Relevant Characteristics

2021 ◽  
Vol 8 ◽  
Author(s):  
Qixuan Wang ◽  
Minfei Qian ◽  
Lu Yang ◽  
Junbo Shi ◽  
Yingying Hong ◽  
...  
Keyword(s):  
Cluster Analysis ◽  
Hearing Loss ◽  
Noise Exposure ◽  
Multinomial Logistic Regression ◽  
Eastern China ◽  
Normal Hearing ◽  
The Other ◽  
Data Driven ◽  
Noise Induced Hearing Loss ◽  
History Of

Background: The definition of notched audiogram for noise-induced hearing loss (NIHL) is presently based on clinical experience, but audiometric phenotypes of NIHL are highly heterogeneous. The data-driven clustering of subtypes could provide refined characteristics of NIHL, and help identify individuals with typical NIHL at diagnosis.Methods: This cross-sectional study initially recruited 12,218 occupational noise-exposed employees aged 18–60 years from two factories of a shipyard in Eastern China. Of these, 10,307 subjects with no history of otological injurie or disease, family history of hearing loss, or history of ototoxic drug use were eventually enrolled. All these subjects completed health behavior questionnaires, cumulative noise exposure (CNE) measurement, and pure-tone audiometry. We did data-driven cluster analysis (k-means clustering) in subjects with hearing loss audiograms (n = 6,599) consist of two independent datasets (n = 4,461 and n = 2,138). Multinomial logistic regression was performed to analyze the relevant characteristics of subjects with different audiometric phenotypes compared to those subjects with normal hearing audiograms (n = 3,708).Results: A total of 10,307 subjects (9,165 males [88.9%], mean age 34.5 [8.8] years, mean CNE 91.2 [22.7] dB[A]) were included, 3,708 (36.0%) of them had completely normal hearing, the other 6,599 (64.0%) with hearing loss audiograms were clustered into four audiometric phenotypes, which were replicable in two distinct datasets. We named the four clusters as the 4–6 kHz sharp-notched, 4–6 kHz flat-notched, 3–8 kHz notched, and 1–8 kHz notched audiogram. Among them, except for the 4–6 kHz flat-notched audiogram which was not significantly related to NIHL, the other three phenotypes with different relevant characteristics were strongly associated with noise exposure. In particular, the 4–6 kHz sharp-notched audiogram might be a typical subtype of NIHL.Conclusions: By data-driven cluster analysis of the large-scale noise-exposed population, we identified three audiometric phenotypes associated with distinct NIHL subtypes. Data-driven sub-stratification of audiograms might eventually contribute to the precise diagnosis and treatment of 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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