Tranylcypromine upregulates Sestrin 2 expression to ameliorate NLRP3-related noise-induced hearing loss

Noise-induced hearing loss is the primary non-genetic factor contributing to auditory dysfunction.However,there are currently no effective pharmacological interventions for patients with noise-induced hearing loss.Here,we present evidence suggesting that the lysine-specific demethylase 1 inhibitor–tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss,and elucidate its underlying regulatory mechanisms.We established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 d B for 4 hours.We found that tranylcypromine treatment led to the upregulation of Sestrin2(SESN2)and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with tranylcypromine.The noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click,4,8,and 16 k Hz frequencies compared with the noise exposure group treated with saline.These findings indicate that tranylcypromine treatment resulted in increased SESN2,light chain 3B,and lysosome-associated membrane glycoprotein 1 expression after noise exposure,leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3,thereby reducing noise-induced hair cell loss.Additionally,immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy pathway.Tranylcypromine treatment also reduced the production of NOD-like receptor family pyrin domaincontaining 3(NLRP3)production.In conclusion,our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2,which induced autophagy,thereby restricting NLRP3-related inflammasome signaling,alleviating cochlear hair cell loss,and protecting hearing function.These findings suggest that inhibiting lysine-specific demethylase 1 is a potential therapeutic strategy for preventing hair cell loss and noise-induced hearing loss.

Prevalence of Noise-Induced Hearing Loss Related to the Mills in the Markets of the Municipality of Parakou in 2021

Introduction: Noise is the second leading cause of hearing loss in adults after presbycusis. The objective of this work was to study hearing loss induced by the noise of mills in the markets of Parakou. Methods: This was a descriptive and analytical cross-sectional study, conducted from February 3 to June 3, 2021 in the markets of Parakou. It concerned millers and sellers located within a 5 meter radius around the mills and among whom pure-tone audiometry was performed to detect a hearing loss. Subjects with no particular medical health history, under 55 years of age and having been working in these markets since more than 12 months, were included. Results: In this study, 103 subjects were selected, including 43 millers and 61 sellers. Their average age was 29 ± 13 years. The sex ratio was 0.49. The average length of service in the profession was 8 years with the extremes of 3 months and 47 years. They were exposed to noise on average 10 hours per day and 6 days a week. The average duration of weekly noise exposure was 23 h 28 min ± 13 h 32 min with the extremes of 5 h 00 min and 52 h 30 min. The average level of noise exposure was 90 dB with the extremes of 72 and 110 dB. 24 subjects reported symptoms related to noise such as headache, tinnitus, and hearing loss, with respective proportions of 22.33%, 20.39% and 06.80%. The prevalence of noise-related hearing loss was 26.21% (n = 27/103). Subjects with a notch at 4000 Hz and normal Average Hearing Loss (AHL) (20.39%) had a seven-time greater risk of developing noise-induced hearing loss (OR = 6.58;95% CI [2.54 - 18.8], p Conclusion: Hearing loss related to the noise of mills affected both millers and sellers near the mills in markets, hence the importance of regulating mills.

Evaluation of Digits-in-Noise Test and Hearing Handicap Inventory for Adults Screening in Patients with Occupational Noise-Induced Hearing Loss

Objective:To explore the clinical evaluation role of the Digits-in-Noise(DIN)test and Hearing Handicap Inventory for Adults Screening(HHIA-S)for patients with occupational noise-induced hearing loss and to observe and analyze their application values.Methods:Fifty patients with suspected occupational noise-induced hearing loss were randomly selected from the Department of Otolaryngology at the hospital as the research target.The collection period for the research cases spanned from January 2022 to November 2023,and all patients had a history of noise exposure.The DIN test and HHIA-S were used for hearing examinations,with clinical,comprehensive diagnosis serving as the gold standard to study their diagnostic performance.Results:The compliance rate of the DIN test was 88.00%,the HHIA-S’s compliance rate was 80.00%,and the combined compliance rate was 94.00%.The compliance rate of the DIN test and the combined compliance rates of the patients were statistically significant compared to the clinical gold standard data(P<0.05),while there was no difference between the compliance rate of the HHIA-S and the gold standard(P>0.05).The data shows that the sensitivity of the combined diagnosis is significantly higher than the sensitivity data of the DIN test and HHIA-S examination alone(P<0.05).Its specificity is 100.00%,and the accuracy data of the joint diagnosis in the degree were higher than those of the DIN test alone(P>0.05)and the HHIA-S alone(P<0.05).Conclusion:For patients with occupational noise-induced hearing loss,the joint evaluation of the DIN test and HHIA-S can significantly improve their diagnostic value with high sensitivity and accuracy.

Early detection of noise-induced hearing loss

BACKGROUND Noise-induced hearing loss(NIHL)is the second most common acquired hearing loss following presbycusis.Exposure to recreational noise and minimal use of hearing protection increase the prevalence of NIHL in young females.NIHL is irreversible.Identifying minor hearing pathologies before they progress to hearing problems that affect daily life is crucial.AIM To compare the advantages and disadvantages of extended high frequency(EHF)and otoacoustic emission and determine an indicator of hearing pathologies at the early sub-clinical stage.METHODS This cross-sectional study was implemented in West China Hospital of Sichuan University from May to September 2019.A total of 86 participants,aged 18-22 years,were recruited to establish normative thresholds for EHF.Another 159 adults,aged 18-25 years with normal hearing(0.25-8 kHz≤25 dBHL),were allocated to low noise and noise exposure groups.Distortion otoacoustic emission(DPOAE),transient evoked otoacoustic emissions(TEOAE),and EHF were assessed in the two groups to determine the superior technique for detecting early-stage noise-induced pathologies.The chi-square test was used to assess the noise and low noise exposure groups with respect to extended high-frequency audiometry(EHFA),DPOAE,and TEOAE.P≤0.05 was considered statistically significant.RESULTS A total of 86 participants(66 females and 20 males)aged between 18 and 22(average:20.58±1.13)years were recruited to establish normative thresholds for EHF.The normative thresholds for 9,10,11.2,12.5,14,16,18,and 20 kHz were 15,10,20,15,15,20,28,and 0 dBHL,respectively.A total of 201 participants were recruited and examined for eligibility.Among them,159 adults aged between 18 and 25 years were eligible in this study.No statistical difference was detected between the noise exposure and the low noise exposure groups using EHFA,DPOAE,and TEOAE(P>0.05)except in the right ear at 4 kHz using TEOAE(abnormal rate 20.4%vs 5.2%,respectively;P=0.05).CONCLUSION These results showed TEOAE as the earliest indicator of minor pathology compared to DPOAE and EHFA.However,a multicenter controlled study or prospective study is essential to verify these results.

Involvement of NLRP3-inflammasome pathway in noise-induced hearing loss

The inflammasome is a multiprotein oligomer in the cell cytoplasm and is part of the innate immune system.It plays a crucial role in the pathological process of noise-induced hearing loss(NIHL).However,the mechanisms of NLR family pyrin domain containing 3(NLRP3)inflammasome activation in NIHL have not been clearly demonstrated.In this study,miniature pigs were exposed to white noise at 120 dB(A)and auditory brainstem response measurements were used to measure their hearing function.Immunofluorescence staining,confocal laser scanning microscopy,western blot assay,and quantitative reverse transcription-polymerase chain reaction were used to analyze inflammasome-related protein distribution and expression.NLRP3,interleukin-1β,interleukin-18,and cleaved-caspase-1 were highly expressed in the cochlea after 120 dB(A)white noise exposure.Our findings suggest that NLRP3-inflammasomes in the cochlea may be activated after acoustic trauma,which may be an important mechanism of noise-induced hearing loss.

Saturated hydrogen saline protects against noise-induced hearing loss

Objective To study effects of saturated hydrogen saline in preventing noise-induced hearing loss. Methods Fifteen guinea pigs were randomly divided into 3 groups （5 each）, group one was for control, group two was treated with normal saline and group three was treated with saturated hydrogen saline, which was given intraperitoneally at 1 hour before noise exposure at 1 ml/100 g. One hundred rounds of impulse noise （ 157 dB SPL peak） were delivered as noise exposure. Immediately after exposure to impulse noise and on Days 1, 2, 4 and 8 following exposure, auditory brainstem response （ABR） thresholds were measured. Outer hair cell morphological changes and sueeinate dehydrogenase （SDH） activity were examined on Day 8 post-exposure. Results Immediately after noise exposure, ABR thresholds in saturated hydrogen saline treated animals were lower than the non-treated animals （P 〈 0.05 ）. Microscopy showed little SDH staining, cell swelling and irregular cell arrangement in the non-treated or normal saline treated animals. Whereas in the saturated hydrogen saline treated animals, there was deep SDH staining with significantly reduced cell loss and more regular cellular arrangement compared to the other two groups. The surviving cells counts was 45.17 ±12.15 for non-treated animals, 44.50 ±10.02 for normal saline treated animals and,116.50±2.38 for animals treated with saturated hydrogen saline. While the count was similar between non-treated and normal saline treated animals, it was significantly higher in saturated sions Intraperitoneal injection of saturated hydrogen saline damage. hydrogen saline treated animals （P 〈 0.05）. Concluappears to protect the cochlea against noise-induced damage.

NRN1 and CAT Gene Polymorphisms, Complex Noise, and Lifestyles interactively Affect the Risk of Noise-induced Hearing Loss

Objective The effects of interactions between genetic and environmental factors on the noise-induced hearing loss(NIHL)are still unclear.This study aimed to assess interactions among gene polymorphisms,noise metrics,and lifestyles on the risk of NIHL.Methods A case-control study was conducted using 307 patients with NIHL and 307 matched healthy individuals from five manufacturing industries.General demographic data,lifestyle details,and noise exposure levels were recorded.The Kompetitive allele-specific polymerase chain reaction(KASP)was used to analyze the genotypes of 18 SNPs.Results GMDR model demonstrated a relevant interaction between NRN1 rs3805789 and CAT rs7943316(P=0.0107).Subjects with T allele of rs3805789 or T allele of rs7943316 had higher risks of NIHL than those with the SNP pair of rs3805789-CC and rs7943316-AA(P<0.05).There was an interaction among rs3805789,rs7943316,and kurtosis(P=0.0010).Subjects exposed to complex noise and carrying both rs3805789-CT and rs7943316-TT or rs3805789-CT/TT and rs7943316-AA had higher risks of NIHL than those exposed to steady noise and carrying both rs3805789-CC and rs7943316-AA(P<0.05).The best six-locus model involving NRN1 rs3805789,CAT rs7943316,smoking,video volume,physical exercise,and working pressure for the risk of NIHL was found to be the interaction(P=0.0010).An interaction was also found among smoking,video volume,physical exercise,working pressure,and kurtosis(P=0.0107).Conclusion Concurrence of NRN1 and CAT constitutes a genetic risk factor for NIHL.Complex noise exposure significantly increases the risk of NIHL in subjects with a high genetic risk score.Interactions between genes and lifestyles as well as noise metrics and lifestyles affect the risk of NIHL.

Noise-induced hearing loss in the 21^(st) century: A research and translational update

Millions of people worldwide are exposed to harmful levels of noise daily in their work and leisure environment. This makes noise-induced hearing loss(NIHL) a major occupational health risk globally. NIHL is the second most common form of acquired hearing loss after agerelated hearing loss and is itself a major contributing factor to presbycusis. Temporary threshold shifts, once thought to be relatively harmless and recoverable, are now known to cause permanent cochlear injury leading to permanent loss of hearing sensitivity. This article reviews the current understanding of the cellular and molecular pathophysiology of NIHL with latest findings from animal models. Therapeutic approaches to protect against or to mitigate NIHL are discussed based on their proposed action against these known mechanisms of cochlear injury. Successes in identifying genes that predispose individuals to NIHL by candidate gene association studies are discussed with matched gene knockout animal models. This links to exciting developments in experimental gene therapy to replace and regenerate lost hair cells and post-noise otoprotective therapies currently being investigated in clinical trials. The aim is to provide new insights into current and projected future strategies to manage NIHL; bench to bedside treatment is foreseeable in the next 5 to 10 years.

Andrographolide Attenuates Noise-Induced Hearing Loss by Ameliorating Cochlear Inflammation

Objective:This study aimed to explore andrographolide's mechanism of action and its protective effect on noise-induced hearing loss(NIHL).Materials and Methods:A mice animal model for NIHL was established through exposure to broadband noise at 120 d B sound pressure level for 4 h.Transcriptomics analysis and pharmacodynamic experiments were carried out.Results:Andrographolide enters the inner ear and effectively prevents hearing damage following noise exposure in the mice model for permanent hearing loss.Moreover,treatment with andrographolide inhibited the excessive activation of inflammatory factors in the cochleae of noise-exposed mice.Conclusion:Andrographolide might be a promising candidate for auditory protective drug investigation.

Genetically modified pigs:Emerging animal models for hereditary hearing loss

Hereditary hearing loss(HHL),a genetic disorder that impairs auditory function,significantly affects quality of life and incurs substantial economic losses for society.To investigate the underlying causes of HHL and evaluate therapeutic outcomes,appropriate animal models are necessary.Pigs have been extensively used as valuable large animal models in biomedical research.In this review,we highlight the advantages of pig models in terms of ear anatomy,inner ear morphology,and electrophysiological characteristics,as well as recent advancements in the development of distinct genetically modified porcine models of hearing loss.Additionally,we discuss the prospects,challenges,and recommendations regarding the use pig models in HHL research.Overall,this review provides insights and perspectives for future studies on HHL using porcine models.

Ionically Imprinting-Based Copper(Ⅱ)Label-Free Detection for Preventing Hearing Loss

Copper is a microelement with important physiological functions in the body.However,the excess copper ion(Cu^(2+))may cause severe health problems,such as hair cell apoptosis and the resultant hearing loss.Therefore,the assay of Cu^(2+)is important.We integrate ionic imprinting technology(IIT)and structurally colored hydrogel beads to prepare chitosan-based ionically imprinted hydrogel beads(IIHBs)as a low-cost and high-specificity platform for Cu^(2+)detection.The IIHBs have a macroporous microstructure,uniform size,vivid structural color,and magnetic responsiveness.When incubated in solution,IIHBs recognize Cu^(2+)and exhibit a reflective peak change,thereby achieving label-free detection.In addition,benefiting from the IIT,the IIHBs display good specificity and selectivity and have an imprinting factor of 19.14 at 100μmol·L^(-1).These features indicated that the developed IIHBs are promising candidates for Cu^(2+)detection,particularly for the prevention of hearing loss.

Modified intratympanic steroid therapy for sudden sensorineural hearing loss via tympanic tube and gelfoam as a salvage treatment

Background: Sudden sensorineural hearing loss(SSNHL) is a prevalent emergency in ear, nose, and throat practice. Previous studies have demonstrated that intratympanic steroid therapy(IST) can serve as a salvage treatment for SSNHL after the failure of systemic steroid therapy(SST).Objective: This study aimed to analyze the efficacy of modified IST involving the insertion of a tympanic tube and gelfoam as a salvage treatment for patients with SSNHL, and to explore its associated factors.Methods: Totally, 74 patients who were aged 22–81 years with SSNHL were enrolled and allocated to either the control group(n = 25) or the treatment group(n = 49) based on their treatment modalities. All patients received SST lasting for at least 7 days. Subsequently, patients in the treatment group, after SST failure, underwent IST twice a week for 2–6 weeks, while the control group did not. Efficacy was assessed by the improvement in pure tone average at the affected frequency at the beginning and end of IST.Results: Hearing improvement in all patients after IST in the treatment group was 9.71 ± 14.84 dB, with significant improvement at affected frequencies(250-8000 Hz) compared with the control group(P < 0.05). The findings indicated the duration from the onset of SSNHL to the beginning of IST as an independent factor for pure tone average improvement after treatment(P = 0.002), whereas age, duration of SST, and time of IST were not(P > 0.05).Conclusion: The modified IST was demonstrated to be a safe and effective method as a salvage treatment for SSNHL. This study explored the efficacy of a modified IST approach, incorporating the utilization of tympanic tubes and gelfoam as key components. The findings underscore the advantages of gelfoam as a strategic drug carrier placed in the round window niche. By minimizing drug loss, extending action time, and increasing perilymph concentration, gelfoam enhances the therapeutic impact of IST, contributing to improved hearing outcomes in patients with SSNHL.

Additional comments on foot reflexology treatment for sensorineural hearing loss in infant

Currently,treatment options for infant sensorineural hearing loss(SNHL)are limited.This article describes a novel case of SNHL in an infant successfully treated with foot reflexology,along with observed brain activity changes before and after treatment,as indicated by functional magnetic resonance imaging.Hence,this commentary discusses the case and our viewpoints regarding foot reflexology for treating SNHL.

Effect of foot reflexology on an infant with sensorineural hearing loss:A case report

BACKGROUND Our study contributes to the further understanding of the mechanism of foot reflexology.Foot reflexology has been reported to affect hearing recovery,but no physiological evidence has been provided.This lack of evidence hampers the acceptance of the technique in clinical practice.CASE SUMMARY A girl was taken to North Sichuan Medical University Affiliated Hospital for a hearing screen by her parents.Her parents reported that her hearing level was the same as when she was born.The girl was diagnosed with sensorineural hearing loss(SNHL)by a doctor in the otolaryngology department.After we introduced the foot reflexology project,the parents agreed to participate in the experiment.After 6 months of foot reflexology treatment,the hearing threshold of the girl recovered to a normal level,below 30 dB.CONCLUSION Foot reflexology should be encouraged in clinical practice and for families of infants with SNHL.

Navigating Silence: A Comprehensive Review of Parental Roles in the Rehabilitation of Children with Hearing Loss

This narrative literature review delves into the multifaceted realm of parental involvement in the rehabilitation of children with permanent hearing loss. While existing research has made strides in elucidating parental roles in this context, critical gaps persist, necessitating a comprehensive exploration to inform future endeavors. Our review synthesizes a wide array of studies, identifying these gaps and emphasizing the significance of addressing them. Themes emerging from the literature include the varying degrees of parental engagement, the impact of cultural and socio-economic factors, and the challenges faced by families navigating rehabilitation processes. The synthesis of this literature not only highlights the current state of knowledge but also provides a roadmap for future research efforts. By addressing these gaps, we aim to contribute to a more nuanced understanding of parental involvement in the rehabilitation of children with permanent hearing loss, ultimately fostering improved support systems and holistic care for affected families.

Clinical characteristics and analysis of vestibular-evoked myogenic potentials in patients with sudden sensorineural hearing loss in different ages

BACKGROUND Numerous studies have found that patients experiencing sudden sensorineural hearing loss(SSHL),with or without accompanying vertigo,often show impaired vestibular function.However,there is a dearth of studies analyzing vestibularevoked myogenic potentials(VEMPs)in SSHL patients across various age groups.AIM To investigate vestibular condition in SSHL patients across various age demographics.METHODS Clinical data of 84 SSHL patients were investigated retrospectively.Audiometry,cervical vestibular evoked myogenic potentials(c-VEMPs),and ocular vestibular evoked myogenic potentials(o-VEMPs)were conducted on these patients.Parameters assessed included the latencies of P1 and N1 waves,as well as the amplitudes of P1–N1 waves.Moreover,the study evaluated the influence of factors such as sex,affected side,configuration of hearing loss,and presence of accompanying vertigo.RESULTS Among the 84 SSHL patients,no significant differences were observed among the three groups in terms of gender,affected side,and the presence or absence of vertigo.Group II(aged 41–60 years)had the highest number of SSHL cases.The rates of absent o-VEMPs in the affected ears were 20.83%,31.58%,and 22.72%for the three age groups,respectively,with no statistically significant difference among them.The rates of absent c-VEMPs in the affected ears were 8.3%,34.21%,and 18.18%for the three age groups,respectively,with significant differences.In the unaffected ears,there were differences observed in the extraction rates of o-VEMPs in the unaffected ears among the age groups.In the three age groups,no significant differences were noted in the three age groups in the latencies of P1 and N1 waves or in the amplitude of N1–P1 waves for c-VEMPs and o-VEMPs,either on the affected side or on the unaffected side,across the three age groups.CONCLUSION The extraction rate of VEMPs is more valuable than parameters.Regardless of the presence of vertigo,vestibular organs are involved in SSHL.Notably,SSHL patients aged 41–60 appear more susceptible to damage to the inferior vestibular nerve and saccule.

Therapeutic efficacy of methylprednisolone sodium succinate via diverse administration routes for mid-to high-frequency sudden sensorineural hearing loss

BACKGROUND Sudden sensorineural hearing loss(SSNHL),characterized by a rapid and unexplained loss of hearing,particularly at moderate to high frequencies,presents a significant clinical challenge.The therapeutic use of methylprednisolone sodium succinate(MPSS)via different administration routes,in combination with conventional medications,remains a topic of interest.AIM To compare the therapeutic efficacy of MPSS administered via different routes in combination with conventional drugs for the treatment of mid-to high-frequency SSNHL.METHODS The medical records of 109 patients with mid-to high-frequency SSNHL were analyzed.The patients were divided into three groups based on the route of administration:Group A[intratympanic(IT)injection of MPSS combined with mecobalamin and Ginkgo biloba leaf extract injection],Group B(intravenous injection of MPSS combined with mecobalamin and Ginkgo biloba leaf extract injection),and Group C(single IT injection of MPSS).The intervention effects were compared and analyzed.RESULTS The posttreatment auditory thresholds in Group A(21.23±3.34)were significantly lower than those in Groups B(28.52±3.36)and C(30.23±4.21;P<0.05).Group A also exhibited a significantly greater speech recognition rate(92.23±5.34)than Groups B and C.The disappearance time of tinnitus,time to hearing recovery,and disappearance time of vertigo in Group A were significantly shorter than those in Groups B and C(P<0.05).The total effective rate in Group A(97.56%)was significantly greater than that in Groups B and C(77.14%and 78.79%,χ^(2)=7.898,P=0.019).Moreover,the incidence of adverse reactions in Groups A and C was significantly lower than that in Group B(4.88%,3.03%vs 2.57%,χ^(2)=11.443,P=0.003),and the recurrence rate in Group A was significantly lower than that in Groups B and C(2.44%vs 20.00%vs 21.21%,χ^(2)=7.120,P=0.028).CONCLUSION IT injection of MPSS combined with conventional treatment demonstrates superior efficacy and safety compared to systemic administration via intravenous infusion and a single IT injection of MPSS.This approach effectively improves patients'hearing and reduces the risk of disease recurrence.

Social Effects of Hearing Loss on Patients in Jos, North Central Nigeria

Hearing loss has caused serious social effects among people living with it. Those who relate to patients with hearing loss (PHL) also share some part of the negative effects. Some specifics are communication disability, which impacts speech and language development, academic performance, and social or work life. In previous years, the problem was predicted to be aggravated as the expected life span of the population increased. The study was conducted among PHL and their family members in JUTH and Kazahyet Audiology Service in Jos. 150 PHL were purposively sampled. The study was guided by a Cross-sectional Survey Research Design, and the specific objectives were to (1) identify the social effects of hearing loss on the PHL, (2) determine the implication of social effects on PHL, and (3) determine the extent at which these social effects affect PHL. The outcome of the study shows that the social effects faced by PHL are poor relationships, no secrets, dependence on sign language, frustration, depression, and dependence on lip reading. Some stop schooling, and others feel laughed at and therefore choose the path of isolation. The implication is that hearing loss is expensive to manage. PHL always feel they are not contributing their quarter in life as usual;they feel stigmatized and are not easy to relate with. The study recommends that the government should come up with policies that will check man-made behaviors that exert negative social effects on PHL in our society, subsidize the cost of hearing aids and cochlear implants to be affordable for PHL, formulate a policy on mandatory newborn hearing screening before the infant is discharged from the hospital to help in the early identification of hearing loss. Finally, the early creation of awareness of the dangers or consequences of hearing loss will go a long way in preventing our society from involvement in high-risk behaviors that will cause hearing loss.

Prophylactic effect of Ca^(2+)-deficient artificial perilymph perfusion on noise-induced hearing loss

Objective To investigate the prophylactic effect of low calcium concentration perilymph on noise-induced hearing loss. Methods Forty guinea pigs with normal hearing weighing 250-350 g were assigned to five groups (8 in each group): (1) Ca2+-deficient perilymph perfusion (CDP) for 2 h; (2) white noise (120 dB SPL) exposure (WNE) only for 1 h, (3) combination of calcium-deficient perilymph perfusion and white noise (120 dB SPL) exposure (WNE+CDP); (4) normal artificial perilymph (NAP) perfusion for 2 h; and (5) white noise exposure + normal artificial perilymph perfusion (WNE+NAP) for 2 h. Compound action potentials (CAP) evoked by click was recorded from round window every 15 min. The cochleae from 5 animals in each group were examined with scanning electron microscope. Results The CAP for group 1 experienced a threshold shift (TS) of 15-26 dB, while group 2 yielded a 46-59 dB TS and group 3 a 37-45 dB TS; no threshold shift occurred in group 4. The CAP TS in group 5 was 33-64 dB. The CAP TS of group 3 was less than that of group 2. After one hour of noise exposure, the CAP TS of group 3 were 45.92±2.90 dB and 59.30±3.95dB in group 2. There were significant differences (P<0.05) between groups 3 and 2. The CAP TS of group 3 was less than that of group 5 at the points of 1, 1.5 and 2 h after noise exposure. There was a significant difference between groups 3 and 5 (P<0.01). Stereocilia of 89 OHC3 were in disarray in five cochleae after noise exposure in group 2. The cuticular plates of 8 OHC2,3 sank and the stereocilia became fused in only one animal cochlea after noise exposure in group 3 combined with low calcium perilymph perfusion. Conclusions Low calcium concentration appears to participate in preventing noise-induced hearing loss and the rising of calcium concentrations in inner hair cells after noise exposure, which may have been due to the opening of calcium channels in inner hair cells during noise exposure. The mechanism of the prophylactic effect might be caused by a lower calcium concentration in inner hair cells in the cochlea attenuating the influence of noise exposure on hearing loss; calcium deficient perilymph perfusion prevented calcium accumulation in inner hair cells of the cochlea. The motility of the OHCs might be partially inhibited by low calcium concentration that reduced noise-induced hearing loss in turn.

Glucose Protects Cochlear Hair Cells Against Oxidative Stress and Attenuates Noise-Induced Hearing Loss in Mice

Oxidative stress is the key determinant in the pathogenesis of noise-induced hearing loss(NIHL). Given that cellular defense against oxidative stress is an energyconsuming process, the aim of the present study was to investigate whether increasing energy availability by glucose supplementation protects cochlear hair cells against oxidative stress and attenuates NIHL. Our results revealed that glucose supplementation reduced the noiseinduced formation of reactive oxygen species(ROS) and consequently attenuated noise-induced loss of outer hair cells, inner hair cell synaptic ribbons, and NIHL in CBA/J mice. In cochlear explants, glucose supplementation increased the levels of ATP and NADPH, as well as attenuating H_2O_2-induced ROS production and cytotoxicity. Moreover, pharmacological inhibition of glucose transporter type 1 activity abolished the protective effects of glucose against oxidative stress in HEI-OC1 cells. These findings suggest that energy availability is crucial for oxidative stress resistance and glucose supplementation offers a simple and effective approach for the protection of cochlear hair cells against oxidative stress and NIHL.