Basic and applied aspects of noise-induced hearing loss: R.J. Salvi, D. Henderson, R.P. Hamernik and V. Colletti (Eds.) (Plenum, New York, 1986, 666 p., U.S. $97.50)

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.

Hearing loss is a major disability in everyday life and therapeutic interventions to protect hearing would benefit a large portion of the world population. Here we found that mice devoid of the protein kinase suppressor of RAS 1 (KSR1) in their tissues (germline KO mice) exhibit resistance to both cisplatin- and noise-induced permanent hearing loss compared with their wild-type KSR1 littermates. KSR1 is a scaffold protein that brings in proximity the mitogen-activated protein kinase (MAPK) proteins BRAF, MEK1/2 and ERK1/2 and assists in their activation through a phosphorylation cascade induced by both cisplatin and noise insults in the cochlear cells. KSR1, BRAF, MEK1/2, and ERK1/2 are all ubiquitously expressed in the cochlea. Deleting the KSR1 protein tempered down the MAPK phosphorylation cascade in the cochlear cells following both cisplatin and noise insults and conferred hearing protection of up to 30 dB SPL in three tested frequencies in male and female mice. Treatment with dabrafenib, an FDA-approved oral BRAF inhibitor, protected male and female KSR1 wild-type mice from both cisplatin- and noise-induced hearing loss. Dabrafenib treatment did not enhance the protection of KO KSR1 mice, providing evidence dabrafenib works primarily through the MAPK pathway. Thus, either elimination of the KSR1 gene expression or drug inhibition of the MAPK cellular pathway in mice resulted in profound protection from both cisplatin- and noise-induced hearing loss. Inhibition of the MAPK pathway, a cellular pathway that responds to damage in the cochlear cells, can prove a valuable strategy to protect and treat hearing loss.

본 연구는 소음성 감각신경성난청 환자의 유전적 관련요인을 파악하고자 관련성이 의심되는 mitochondrial DNA의 돌연변이와 소음성 감각신경성난청과의 관련성을 조사하였다. 말초혈액 백혈구로부터 DNA를 추출한 후, mtDNA 3243, 1555, 7445부위의 <TEX>$A{\rightarrow}G$</TEX> 돌연변이 유무를 관찰하기 위하여 mtDNA 3243, 1555, 7445부위 가 포함된 mtDNA fragment를 중합효소 연쇄반응으로 증폭하고 유전자 제한효소로 소화하여 전기영동하고 ethidium bromide 용액으로 염색하여 UV transilluminator에서 관찰하였다. 그리고, PCR 산물을 이용하여 DNA 염기서열을 분석하여 mtDNA 3243, 1555, 7445부 위에서의 염기서열 분석을 실시하여 mtDNA 3243, 1555, 7445부위 의 <TEX>$A{\rightarrow}G$</TEX> 돌연변이를 관찰하였다 MtDNA A3243G, A1555G, A7445G의 돌연변이를 관찰한 결과 돌연변이 부위가 포함된 fragment가 소음성 감각신경성난청 환자군, 감각신경성난청 환자군, 대조군 모두에서 증폭됨을 관찰하였다. 또한 PCR 산물을 제한효소로 처 리 한 결과에서도 mtDNA에서 3243, 1555, 7445부위의 <TEX>$A{\rightarrow}G$</TEX> 돌연변이가 일어나지 않았음을 알 수 있었다. PCR산물을 이용하여 DNA 염기서열을 분석하여 mtDNA 3243, 1555, 7445부위에서의 염기서열을 확인한 결과 이미 밝혀진 사람의 mtDNA 3243, 1555, 7445부 위의 염기서열과 동일한 염기서열임이 확인되었으므로 mtDNA 3243, 1555, 7445부위의 <TEX>$A{\rightarrow}G$</TEX> 돌연변이가 일어나지 않았음을 확인하였다. 소음성 감각신경성난청과 mtDNA 3243, 1555, 7445부위의 <TEX>$A{\rightarrow}G$</TEX> 돌연변이와는 관련이 없는 것으로 관찰되었다. Mitochondrial DNA mutations have been reported in recent years in association with sensorineural hering loss. The purpose of this study is to identify the association between the noise-induced sensorineural hearing loss and the A to G mutation at nucleotide 3243, 1555, 7445 of mitochondrial DNA. Study subjects were established by history and chart review, and audiological and clinical data were obtained. Blood was sampled from 214 normal controls, 102 noise-induced hearing loss, and 28 sensorineural hearing loss. The DNA of these individuals were extracted, and mitochondrial DNA fragments were analyzed by polymerase chain reaction. Subsequently, the coding sequence of mitochondrial DNA 3243, 1555, 7445 were sequenced, and compared to the normal sequence, and all sequence variations were analyzed by restriction enzymes. Mitochondrial DNA mutations <TEX>$(3243A{\rightarrow}G,\;1555A{\rightarrow}4G,\;7445A{\rightarrow}G)$</TEX> were not detected by polymerase chain reactions in any patients with noise-induced hearing loss, sensorineural hearing loss, and normal controls. The DNA sequencing of PCR products did not revealed an A to G substitution at nucleotide 3243, 1555, 7445 of mitochondrial DNA. The noise-induced sensorineural hearing loss was not associated with mitochondrial DNA mutation <TEX>$(3243A{\rightarrow}G,\;1555A{\rightarrow}4G,\;7445A{\rightarrow}G)$</TEX>.

More than 5% of the global population suffers from disabling hearing loss, primarily sensorineural hearing loss (SNHL). SNHL is often caused by factors such as vascular disorders, viral infections, ototoxic drugs, systemic inflammation, age-related labyrinthine membrane degeneration, and noise-induced hearing loss (NIHL). NIHL, in particular, leads to changes in blood-labyrinth-barrier (BLB) physiology, increased permeability, and various health issues, including cardiovascular disease, hypertension, diabetes, neurological disorders, and adverse reproductive outcomes. Recent advances in neuromodulation and vector-based approaches offer hope for overcoming biological barriers such as the BLB in the development of innovative treatments. Computational methods, including molecular docking, molecular dynamics simulations, QSAR/QSPR analysis with machine/deep learning algorithms, and network pharmacology, hold potential for identifying drug candidates and optimizing their interactions with BLB transporters, such as the glutamate transporter. This paper provides an overview of NIHL, focusing on its pathophysiology; its impact on membrane transporters, ion channels, and BLB structures; and associated symptoms, comorbidities, and emerging therapeutic approaches. Recent advancements in neuromodulation and vector-based strategies show great promise in overcoming biological barriers such as BLB, facilitating the development of innovative treatment options. The primary aim of this review is to examine NIHL in detail and explore its underlying mechanisms, physiological effects, and cutting-edge therapeutic strategies for its effective management and prevention.

The purpose of this study was to evaluate the differences in cerebral glucose metabolism and metabolic connectivity between noise-induced hearing loss (NIHL) subjects and normal subjects. Eighty-nine subjects who needed close observation for NIHL or were diagnosed with NIHL and 89 normal subjects were enrolled. After pre-processing of positron emission tomography images including co-registration, spatial normalization, and smoothing, a two-sample t-test was conducted to compare cerebral glucose metabolism between the two groups. To evaluate metabolic connectivity between two groups, BRAPH–BRain Analysis using graPH theory, a software package to perform graph theory analysis of the brain connectome was used. NIHL subjects showed hypometabolism compared to normal subjects in both insulae (x − 38, y − 18, z 4; × 42, y − 12, z 4) and right superior temporal gyrus (× 44, y 16, z − 20). No brain regions showed hypermetabolism in the NIHL subjects. In metabolic connectivity analysis, NIHL subjects showed decreased average strength, global efficiency, local efficiency, and mean clustering coefficient when compared with normal subjects. Decreased glucose metabolism and metabolic connectivity in NIHL subject might reflect decreased auditory function. It might be characteristic of sensorineural hearing loss.

Mechanisms of Noise-Induced Hair Cell Death

You have accessThe ASHA LeaderFeature1 Oct 2010Teens at Risk: Audiologists Respond Marat Moore Marat Moore Google Scholar More articles by this author https://doi.org/10.1044/leader.FTR1.15122010.8 SectionsAbout ToolsAdd to favorites ShareFacebookTwitterLinked In Audiologists are weighing in on the research on teen hearing loss published two months ago in the Journal of the American Medical Association (JAMA) and its implications for the profession. The study, described in Part 1 of this series (The ASHA Leader, Sept. 21), showed a 31% overall rise in the prevalence of hearing loss in teens aged 12 to 19 from 1988–1994 to 2005–2006. Most of the hearing loss was slight, between 15 and 25 dB—but the prevalence of mild and worse (25 dB or greater) hearing loss increased 77%. The study also found that unilateral hearing loss was more common than bilateral (for reasons unknown), and that individuals reporting an income below the national poverty level in the 2005–2006 survey cycle had a significant risk of hearing loss. The study’s Aug. 18 publication triggered a media blast—ASHA media efforts alone reached a broadcast and online audience of nearly 45 million people. This media exposure pushed noise-induced hearing loss—and audiologists—into the national spotlight and sparked discussions on how to protect the hearing of young Americans. Audiologists are taking that conversation further, exploring with colleagues and ASHA their ideas for strategies to educate people of all ages about the impact of hazardous noise on hearing health and quality of life. The ASHA Leader interviewed six audiologists in a variety of settings—private practice, academia, occupational audiology, and educational audiology—for their perspectives on the impact of potentially accelerated hearing loss in the rising generation, and for their ideas for next steps audiologists can take to continue to play a visible role in addressing the problem of noise-induced hearing loss. The interviews follow on pages 8–10. What’s their bottom line? These professionals say: The time is ripe for audiologists to make connections in school systems and offer themselves as a resource. Parents need to understand the risk factors and have their child’s hearing screened if the child is in a high-risk group. The cultural dimension in an individual’s exposure to dangerous levels of sound must be considered. Educational audiologists are few in number, and need the support of all audiologists in a unified campaign. School-based speech-language pathologists could help link science teachers and administrators with audiologists in educational outreach to middle schools and high schools. Our goal should be the eradication of noise-induced hearing loss in our children’s lifetime. Audiologists are front and center in this national discussion. In Part 3 of this series, the Leader will profile programs such as ASHA’s “Listen to Your Buds” and others—including “Dangerous Decibels”—and provide a full list of resources to those members committed to making a difference on the issue of noise-induced hearing loss. Brian Fligor, ScD, CCC-A Director of Diagnostic Audiology, Children’s Hospital Boston Instructor in Otology and Laryngology, Harvard Medical School We know that hearing loss is related primarily to two factors—age and noise. Given that the recent JAMA study evaluated teenagers, age-related hearing loss is factored out. So it’s likely from noise—from many sources. It’s not all about headphones. But with 90% of teens using portable listening devices (PLDs), it would not be unreasonable to expect an acceleration of age-related changes in hearing due to what these one in five teens have been doing to their hearing health during their first two decades. What if their lifestyle choices cause them to have hearing more like 30- or 40-year-olds than like teenagers? Their “ear age” may have greatly outpaced their chronological age. That could mean that at age 30 or 40, they may have the hearing of a 50- or 60-year-old. They may need hearing aids at much younger ages. This study also could affect our thinking about the standard of “audiometric zero,” which is based upon screened 18-year-olds who supposedly have pristine hearing. We use that measure to determine our expectations for age-related hearing loss. This study says that one in five teens tested didn’t have pristine hearing—that’s a huge number. The JAMA study was unable to show any causal link for hearing loss, with the exception of children with a lower socioeconomic status. That factor is something we know to have a very robust effect, but it’s hard to explain why your hearing is worse if you are poor. I was concerned about the paper’s inability to show cause and effect related to the use of firearms, which was not shown to be a significant predictor of hearing loss in this study. That finding makes me wonder if the questions they asked were not sensitive enough to show cause, because use of firearms is the leading cause of recreational noise-induced hearing loss (NIHL). Here’s the good thing—because this research appeared in JAMA, hearing health is in the public’s mind. Awareness is a great thing, but it’s important that it not be overblown. The amount of hearing loss is not outrageous. Most of the hearing loss is slight. As a first step, parents need to ensure that teens see an audiologist to establish a baseline hearing level. Audiologists can then recommend a hearing loss prevention program if, for example, a child is playing percussion in a marching band. My message to parents is simple—respect your child’s hearing. People need to take responsibility for hearing health for themselves and their children, but it’s up to us to give them educational tools for making better hearing health decisions. Audiologists also should consult with industry to help develop technical tools that help consumers use their devices more responsibly. Audiologists are uniquely suited to help children and teens get preventive hearing care, not so different from preventive dental care. Musicians, teens who use PLDs heavily, or any at-risk individuals need an audiologist like everyone else needs a dentist. The public awareness brought about by the JAMA research offers us a great opportunity—audiologists could partner with science teachers and speech-language pathologists in the schools, and they could contact their administrators about bringing in an audiologist. We could participate in science fairs in middle school and high school, and we could do in-service training for biology and physics teachers. The time is ripe for audiologists to make connections in the school system and offer ourselves as a resource. Our participation also may encourage some students to have an interest in audiology at a time when there is a critical need to promote careers in audiology and hearing science. Mary McDaniel, AuD, CCC-A Occupational Audiologist Pacific Hearing Conservation Seattle, Wash. For decades we have known the effects of noise on hearing and that noise-induced hearing loss often is preventable. To think that noise-induced hearing loss is primarily an occupational hazard is a misconception. We live and play in a noisy world, and noise damage knows no age boundaries. It is tragic that hearing loss prevention isn’t part of every child’s school curriculum. We must teach our children at an early age about how to prevent noise-induced hearing loss. This effort also can be accomplished through a media campaign that would serve to educate parents and the public. Young people often underestimate the impact of noise and hearing loss on their lives. Even a slight loss can affect an individual’s ability to discriminate sounds, perhaps missing the punch line of a joke or the details of a school assignment. Hearing loss will affect both their social and academic lives, and will be with them throughout their lifespan. The most important strategy that could be implemented through both the media and the nation’s schools is a program of education and motivation about the potential hazard of noise in our lives. There’s absolutely no reason that a school-based SLP could not assist in this process, unless it might be because of a bulging caseload! We also could enlist parents or teachers’ aides to spread the word. One of the most significant things about this research is the attention that it brings to noise-induced hearing loss. This current research illuminates a problem that will affect our society for years to come. Our goal should be to eradicate noise-induced hearing loss in our children’s lifetimes. Janice Trent, AuD, CCC-A Private-practice Audiologist Hearing Health Care Services LLC Bowie, Md. The JAMA research dovetailed with the findings of a report by the Kaiser Family Foundation published in January that looked at the use of all media by children 8 to 18 years old. They found that kids were engaged with entertainment media an average of 7.5 hours a day—using earbuds with all types of media including laptops, television, video games, and personal listening devices like iPods and MP3 players. It’s a bombardment of the auditory system. And classrooms are another source of noise. After doing a radio talk show interview on the impact of the JAMA research, I received an e-mail from a teacher who said he wished we had addressed school cafeteria noise. It was a stressor for him and he wondered about the impact of high noise levels on digestion. We need to make a bigger statement about protecting hearing health—and not just to kids in the schools. The question for adults is, have we been too tolerant of noise? If adults are not modeling hearing conservation, why should we expect our children to protect their ears? We also need to consider the cultural dimension in the audiological context. I’m African American and a preacher’s wife. One of the things I have found is that in many evangelical churches the music is too loud. I have done breakfast workshops with area ministers talking about noise levels, the impact on their congregants, and strategies to change the listening environment. I’m not trying to curtail the spirit, but a 150-voice choir does not need an amplifier set at maximum volume. After another radio talk show interview, a blogger wrote to ask, can you do something about the volume of music at bar mitzvahs? I was reminded that loud music has infiltrated our lives in many different areas. As audiologists, we are the professionals to address publicly the issue of sociocusis in our communities and its impact on the auditory system. We need to talk aggressively about prevention—and not just screening, but a full diagnostic evaluation. Most insurance will pay for that, similar to a complete vision evaluation. We need to start looking more broadly at all environments: classrooms, the workplace, recreational activities, transportation, and the home environment. I applaud the JAMA study, but we also need to let the public know that researchers in our discipline have done great research on these issues. So many people do not understand noise-induced hearing loss or its risk factors. We have to educate the public about the impact of noise. Audiologists are the go-to people on noise-induced hearing loss—we’re out there on the front lines making the diagnoses and encouraging prevention, and with the recent rise in public awareness, it’s time to ramp up our efforts on these issues and try to make a real difference. Dennis Hampton, PhD, CCC-A Private-practice Audiologist Westchester Audiology Center White Plains, N.Y. The JAMA article confirms that hearing loss appears to be on the increase and a significant cause of the increase appears to be hearing loss we inflict on ourselves. Our ears don’t care whether the toxic noise levels are from the factory floor or motorcycle noise, Beethoven or rap. Is the use of personal headsets by teens a cause? Years ago, that question was answered when Maurice Miller, an audiologist from New York, studied the output levels of the Sony Walkman portable tape player (Hearing Loss Magazine, 2006). He found that users of personal headsets often set the Walkman at levels that could damage hearing. Today, it’s MP3 players, plus rock concerts and all the other sources of noise around young adults. We no longer have to debate whether personal headphones (and loud music) causes hearing loss. Our job is to spread that message to other health care providers, educators, and to teens and young adults. This also is an opportunity to reinforce our belief that hearing screening, which takes place in the primary school setting in most states, should be a part of a person’s health examination throughout the lifespan. Unfortunately, only about 10% of physicians actually screen for hearing loss. The publication of this research is an opportunity, then, for us to prevent hearing loss by increasing public awareness, educating health care providers and the public, and encouraging regular hearing screenings. In my practice, we mail newsletters to our patients and local physicians, and we will review this research in an upcoming article, written for physicians, that will address the role of the family physician in screening for and preventing patients’ hearing loss. School-based speech-language pathologists and educational audiologists could have an important role in bringing this research to the attention of science teachers--and school nurses and health teachers. Hearing loss prevention could be incorporated into the science and health curricula. Local SLPs might also recruit a local audiologist as the hearing expert to talk to students in science and health classes. And why not invite an audiologist to be the commencement speaker at graduation! Graduates, go out into the world--but protect your hearing! John Ribera, PhD, CCC-A Director of Audiology Department of Communicative Disorders and Deaf Education Utah State University Logan, Utah With the development of portable devices that deliver favorite tunes, there is nothing to dampen the sound between the transducers of these devices (earphones that fit in the concha) and the eardrum. If there is high ambient noise, the tendency is to mask the unwanted sounds by raising the volume even higher. If we fail to turn the tide, adolescents and young adults will begin to experience hearing loss much earlier in life, a condition that is crucial because their academic performance can be adversely affected. Hearing loss also can affect daily activities, social interactions, career progression, and quality of life. We must do more to educate and motivate our youth to think about exposure to dangerous levels of noise. This effort needs to be a multifaceted approach that targets not just youth, but also parents, teachers, and administrators, and other groups that reach young people to help create a new culture and way of thinking about hearing conservation. In Europe there is pressure to require manufacturers of personal listening devices to cap volume levels. This approach might be one to consider in this country. I suggest that young listeners use the 60/60 rule—no higher than 60% of maximum volume for no more than 60 minutes. Classroom presentations on youth hearing health and noise-induced hearing loss can help bring about change. Where there are no educational audiologists, speech-language pathologists could help bring other audiologists to the schools to spread the word. Also, young people usually have heroes in sports and entertainment. The more stars and celebrities who are willing to speak on behalf of hearing conservation, the better. I think ASHA and other organizations have stepped up to the plate by developing materials and websites like “Listen to Your Buds” geared to youthful listeners. Audiologists and speech-language pathologists should always be vocal advocates for hearing conservation and educating the public about the importance of preserving the ability to communicate. Tena McNamara, AuD, CCC-A President-elect, Educational Audiology Association Assistant Professor, Eastern Illinois University When we were growing up, when the stereos went up, the windows went down. Now the sound is going directly into the ears of young people. I work at a special-education co-op and on a college campus, and I see college kids working out in the gym with earbuds on and the levels set at high intensities—which is likely to be a dangerous combination because blood flow increases to the limbs and away from the ears. Some of the oxygen to the cochlea may be depleted, making hair cells more susceptible to noise-induced hearing loss. We need a strong education campaign. It’s hard for educational audiologists—we’re spread so thin. Sometimes we have one professional for every 20,000 to 30,000 students. All audiologists should be involved. We need a team effort led by audiologists with school-based speech-language pathologists, teachers, and administrators. An initial step would be to gather materials and resources to use for in-service training with school districts. We could then implement hearing conservation programs, and put posters and other materials around the schools with the message: Turn it down! Kids are surrounded by electronics, and they don’t realize the consequences to their health. Hearing loss is permanent, and at present there is no cure. Hearing decreases with age, so if you’re starting out with a slight or mild loss at 20, you don’t have the best prognosis. Hearing conservation has been with us for years. We’re really good at promoting it one-on-one, but now we need to step up and expand our efforts and do it in a unified way. This is not just an issue with teenagers. ASHA has the “Listen to Your Buds” campaign that reaches out to young children. We also need to heighten public awareness among adults. We need a public campaign that reaches all age groups. Media Alert for Audiologists Audiologists wishing to connect with media representatives to spread the message about the importance of hearing conservation can contact ASHA’s public relations unit by e-mailing [email protected]. Author Notes Marat Moore, managing editor of The ASHA Leader can be reached at [email protected]. Additional Resources FiguresSourcesRelatedDetails Volume 15Issue 12October 2010 Get Permissions Add to your Mendeley library History Published in print: Oct 1, 2010 Metrics Downloaded 171 times Topicsasha-topicsleader_do_tagleader-topicsasha-article-typesCopyright & Permissions© 2010 American Speech-Language-Hearing AssociationLoading ...

&lt;b&gt;Purpose: &lt;/b&gt;Hearing loss is the loss of hearing function in one or both ears. Noise-induced hearing loss (NIHL) is the second most prevalent type of sensorineural hearing loss, adversely affects the functional and social lives of workers in noisy environments. This study aimed to confirm the relationship between methionine sulfoxide reductase B1 (&lt;i&gt;MSRB1&lt;/i&gt;) expression in the human auditory system and noise exposure by searching for related pathogenic single-nucleotide polymorphisms (SNPs).&lt;br /&gt; &lt;b&gt;Methodology: &lt;/b&gt;The study included 90 workers with NIHL and 90 with normal hearing. A hearing test was administered to each participant, and blood samples were collected from both groups to conduct genetic analyses. A comparison of the genomes of workers with NIHL and those with normal hearing was performed.&lt;br /&gt; &lt;b&gt;Results: &lt;/b&gt;The results showed that rs732510 was found in NIHL participants, while the other SNPs (rs2815304, rs11640479, and rs9934331) were found in both controls and NIHL subjects. Among the NIHL group, 44 participants had heterozygous mutants (TC), 30 had homozygous mutants (CC), and 13 had homozygous wild-type alleles (TT). The heterozygous mutant allele had a statistically significantly higher prevalence (48.9%) compared to the homozygous wild-type allele (14.4%) and homozygous mutant allele (33.3%) among patients with NIHL (χ2[3] = 43.96, p &amp;lt; 0.05).&lt;br /&gt; &lt;b&gt;Conclusion: &lt;/b&gt;This study is the first to report an association between rs732510 in MSRB1 and NIHL in the human auditory system. This finding paves the way for future research to discover more about the gene’s role in the auditory function, suggesting it could be a promising biological biomarker associated with NIHL.

Background:The Ca2+/calmodulin-dependent protein kinase kinases (CaMKKs) are serine/threonine-directed protein kinases that are activated following increases in intracellular calcium, playing a critical role in neuronal signaling. Inner-ear-trauma-induced calcium overload in sensory hair cells has been well-documented in the pathogenesis of traumatic noise-induced hair cell death and hearing loss, but there are no established pharmaceutical therapies available due to a lack of specific therapeutic targets. In this study, we investigated the activation of CaMKKβ in the inner ear after traumatic noise exposure and assessed prevention of noise-induced hearing loss (NIHL) with RNA silencing.Results:Short hairpin RNA of CaMKKβ (shCaMKKβ) via adeno-associated virus transduction significantly knocked down CaMKKβ expression in the inner ear. Knockdown of CaMKKβ significantly attenuated noise-induced hair cell loss and hearing loss (NIHL). Additionally, pretreatment with naked CaMKKβ small interfering RNA (siCaMKKβ) attenuated noise-induced losses of inner hair cell synapses and OHCs and NIHL. Furthermore, traumatic noise exposure activates CaMKKβ in OHCs as demonstrated by immunolabeling for p-CaMKI. CaMKKβ mRNA assessed by fluorescence in-situ hybridization and immunolabeling for CaMKKβ in OHCs also increased after the exposure. Lastly, pretreatment with siCaMKKβ diminished noise-induced activation of AMPKα in OHCs.Conclusions:These findings demonstrate that traumatic-noise-induced OHC loss and hearing loss occur primarily via activation of CaMKKβ. Targeting CaMKKβ is a key strategy for prevention of noise-induced hearing loss. Furthermore, our data suggest that noise-induced activation of AMPKα in OHCs occurs via the CaMKKβ pathway.

Introduction. Noise-induced hearing loss is a rather prevalent condition and can be distressing for a substantial proportion of patients, although researches describing psychological characteristics in noise-induced occupational hearing loss patients are not numerous.The study aims to find the effects of occupational noise on the psychological status among noise-induced hearing loss (NIHL) patients.Methods. Two groups, cross-sectional design. Study sample: 44 occupational noiseinduced male forming NIHL patients group (n = 21) and a control group (n = 23). Both groups were tested using the Russian versions of psychological questionnaires.Results. Almost one third of NIHL patients are the highly anxiety individuals as compared with the healthy participants (p &lt; 0.01). Mixed type of response to the surrounding reality combined a high need for self-actualization with high self-control, tendency to inhibit and restrain behavioral reactions, in this case it is possible to “overlap” both neurotic and behavioral responses, which can affect the general overstrain and manifest by the somatization of the internal conflict. In general, NIHL patients use constructive cognitive, emotional and behavioral coping strategies. Patients use both constructive and tense defense mechanisms. Conclusion. It has been established that in patients with NIHL, in comparison with practically healthy persons, tension accumulates, and a tendency to psychotraumatization appears. However, it is currently difficult to determine whether NIHL is a predisposing factor for these psychological characteristics, so further research is needed to determine how significant this relationship is. Key words: noise-induced hearing loss, occupational noise, psychological profile&gt;˂ 0.01). Mixed type of response to the surrounding reality combined a high need for self-actualization with high self-control, tendency to inhibit and restrain behavioral reactions, in this case it is possible to “overlap” both neurotic and behavioral responses, which can affect the general overstrain and manifest by the somatization of the internal conflict. In general, NIHL patients use constructive cognitive, emotional and behavioral coping strategies. Patients use both constructive and tense defense mechanisms.Conclusion. It has been established that in patients with NIHL, in comparison with practically healthy persons, tension accumulates, and a tendency to psychotraumatization appears. However, it is currently difficult to determine whether NIHL is a predisposing factor for these psychological characteristics, so further research is needed to determine how significant this relationship is.

Eye color as a risk factor for acquired sensorineural hearing loss: A review

The reactive oxygen species (ROS)-generating NADPH oxidase NOX3 isoform is highly and specifically expressed in the inner ear. NOX3 is needed for normal vestibular development but NOX-derived ROS have also been implicated in the pathophysiology of sensorineural hearing loss. The role of NOX-derived ROS in noise-induced hearing loss, however, remains unclear and was addressed with the present study. Two different mouse strains, deficient in NOX3 or its critical subunit p22phox, were subjected to a single noise exposure of 2 h using an 8–16 kHz band noise at an intensity of 116–120 decibel sound pressure level. In the hours following noise exposure, there was a significant increase in cochlear mRNA expression of NOX3 in wild type animals. By using RNAscope in situ hybridization, NOX3 expression was primarily found in the Rosenthal canal area, colocalizing with auditory neurons. One day after the noise trauma, we observed a high frequency hearing loss in both knock-out mice, as well as their wild type littermates. At day seven after noise trauma however, NOX3 and p22phox knockout mice showed a significantly improved hearing recovery and a marked preservation of neurosensory cochlear structures compared to their wild type littermates. Based on these findings, an active role of NOX3 in the pathophysiology of noise-induced hearing loss can be demonstrated, in line with recent evidence obtained in other forms of acquired hearing loss. The present data demonstrates that the absence of functional NOX3 enhances the hearing recovery phase following noise trauma. This opens an interesting clinical window for pharmacological or molecular intervention aiming at post prevention of noise-induced hearing loss.

The clinical application of click-evoked otoacoustic emissions (EOAE) in the assessment of noise-induced hearing loss (NIHL) was examined in a group of 72 ears with NIHL and 61 ears with normal hearing (NH). The characteristics of the EOAE in ears with NIHL significantly differed from the NH, according to all EOAE parameters tested in the present study. The mean overall EOAE level was lower and the mean EOAE nonlinearity threshold was worse in the NIHL group. In 95% of the NH ears the EOAE spectrum range was wide, while in 91.5% of the NIHL ears the range was narrow. Moreover, in 94% of the ears with NIHL, the frequency at which the hearing loss began (BHL) was at or above the frequency of the last peak in the EOAE spectrum (FLP). Furthermore, combination of EOAE spectral measures correctly discriminate on average 93.5% of ears with NH from NIHL (sensitivity) and 92% of ears with NIHL from NH (specificity). In contrast, the nonlinearity threshold and the overall level of EOAE yielded lower specificity of less than 33%. It was therefore concluded that EOAE spectrum may serve as a useful and objective tool in screening adults with suspected noise-induced high frequency hearing loss.

NADH against noise-induced hearing loss: Evidence from models of "temporary" and "permanent" deafness.

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