Cochlear Dysfunction Research Articles

Sensorineural hearing loss in Lyme neuroborreliosis

Background Sensorineural hearing loss (SNHL) has been suggested to occur in patients with Lyme neuroborreliosis (LNB); however, a clear association has never been documented. The present study prospectively investigated the development of SNHL in patients admitted for treatment of LNB using distortion-product-oto-acoustic emissions (DPOAE) as a measure of cochlear function. Methods DOAE were measured in patients with LNB on the day of diagnosis, during treatment, and 30–60 days after discharge. Frequencies were categorized as Low (1, 1.5, 2 kHz), Mid (3, 4, 5 kHz), Mid-high (6, 7, 8 kHz), and High (9, 10 kHz). Pure Tone Audiometry (PTA3) was performed at discharge and 60 days after. Patients were treated with i.v. ceftriaxone or oral doxycycline for 14 days according to guidelines. Results DPOAE measurements were obtained in 25 patients with LNB at admission and in 18 patients at follow-up. Median age was 56 years (IQR, 48–64 years), and 16 (67%) were men. Fourteen (78%) of 18 patients showed improvement in Emission Threshold Levels (ETL) from admission to follow-up in low, mid-, and mid-high frequency categories, where ETLs increased by median levels of 3.2 (−4.1 to 8.3), 7.5 (−2.8 to 9.8), and 4.7 dB (−4.3 to 10.1). A decline was observed in the high frequency category, median −3.3 dB (−9.1 to 6.7). SNHL defined by pure tone average (PTA3) >20 dB was present in 11 out of 23 (48%) at discharge and in 9 out of 16 patients (56%) 60 days after discharge, which differed significantly from matched controls (Mann-Whitney test, p = 0.036). Conclusion LNB can lead to cochlear outer-hair cell dysfunction, resulting in temporary and long-term SNHL.

Assessment of Cochlear Function Among Hypertensive Patients in Bauchi: A Cross-Sectional Cohort Study

Background: Hypertension is an important public-health problem, and it has been identified as the leading cause of morbidity and mortality due to the high incidence of end-organ damages. Unlike other complications of hypertension, cochlear dysfunction in hypertensive patients is a hidden and progressive damage that remains undetected (subclinical) for a long time. The aim of this study was to assess the prevalence of subclinical hearing impairment, as well as the type and degree of hearing loss among hypertensive patients in our environment. Methods: This was a cross-sectional cohort study conducted among adults diagnosed with hypertension previously. Ethical clearance and informed consent were obtained. Previous history of related exposure event (hypertension) and outcome (hearing loss) was assessed. Each participant was then subjected to c-PTA and EHA tests, and findings were analyzed. Results: One hundred and ninety (190) hypertensive patients were enrolled, among which 107 (56.3%) were females and 83 (43.7%) males. Hypertension was more common in the age group of 51-60 years (26.8%) and 61-70 years (30.5%). The overall prevalence of hearing loss was 41.6%, of which 18.4% had subclinical hearing impairment. The most common type of hearing loss was sensorineural 68 (86.1%), found to be in varying degrees of 33.8%, 26.5%, 23.5%, and 16.2% for mild, moderate, severe, and profound hearing loss, respectively. Conclusion: The overall prevalence of hearing loss among hypertensive patients was 41.6%, with a significant proportion (18.4%) having subclinical hearing loss, which is not noticed by the patients. Therefore, routine pure tone audiometric hearing screening for all hypertensives is recommended to enable early detection and treatment of this hearing loss.

SHIMP Findings in Individuals Using Personal Listening Devices.

Listening to PLD at higher volume levels are known to cause subtle pre-clinical damage to the auditory system and vestibular end organs. Exposure to PLDs may also cause vestibular dysfunction much before the cochlear dysfunction. SHIMP is a newly described tool to assess the vestibulo-ocular reflex (VOR) gain suppression. With the premise that prolonged exposure to PLDs at high volume levels may cause vestibular dysfunction, and SHIMP being an early detector of vestibular dysfunction, the study was undertaken. The study aimed to describe the SHIMP test findings in normal hearing individuals with and without prolonged exposure to PLDs at > 60% of volume. A cross sectional comparative study was carried out on 128 participants with and without history of PLD exposure. Participants within the age range of 15-24years and history of PLD usage at < 60% volume for < 1year and at > 60% volume for > 1year were recruited for the study. Output dBSPLs delivered by PLDs were measured using microphone in the ear method. Further, SHIMP was administered to assess the vestibular function. The dBSPL levels used by the participants of both the groups were within the DRC used for occupational noise exposure. Likewise, no statistically significant difference was observed between the two groups. Participants using PLDs with dBSPLs within the DRC may not be at a crucial risk. However, one must use precautionary measures to prevent any subclinical or long-lasting damage to the inner ear.

The Stria Vascularis: Renewed Attention on a Key Player in Age-Related Hearing Loss.

Age-related hearing loss (HL), or presbycusis, is a complex and heterogeneous condition, affecting a significant portion of older adults and involving various interacting mechanisms. Metabolic presbycusis, a type of age-related HL, is characterized by the dysfunction of the stria vascularis, which is crucial for maintaining the endocochlear potential necessary for hearing. Although attention on metabolic presbycusis has waned in recent years, research continues to identify strial pathology as a key factor in age-related HL. This narrative review integrates past and recent research, bridging findings from animal models and human studies, to examine the contributions of the stria vascularis to age-related HL. It provides a brief overview of the structure and function of the stria vascularis and then examines mechanisms contributing to age-related strial dysfunction, including altered ion transport, changes in pigmentation, inflammatory responses, and vascular atrophy. Importantly, this review outlines the contribution of metabolic mechanisms to age-related HL, highlighting areas for future research. It emphasizes the complex interdependence of metabolic and sensorineural mechanisms in the pathology of age-related HL and highlights the importance of animal models in understanding the underlying mechanisms. The comprehensive and mechanistic investigation of all factors contributing to age-related HL, including cochlear metabolic dysfunction, remains crucial to identifying the underlying mechanisms and developing personalized, protective, and restorative treatments.

PARP1 inhibition prevents oxidative stress in age-related hearing loss via PAR-Ca2+-AIF axis in cochlear strial marginal cells

Studies have highlighted oxidative damage in the inner ear as a critical pathological basis for sensorineural hearing loss, especially the presbycusis. Poly(ADP-ribose) polymerase-1 (PARP1) activation responds to oxidative stress-induced DNA damage with pro-repair and pro-death effects resembling two sides of the same coin. PARP1-related cell death, known as parthanatos, whose underlying mechanisms are attractive research hotspots but remain to be clarified. In this study, we observed that aged rats showed stria vascularis degeneration and oxidative damage, and PARP1-dependent cell death was prominent in age-related cochlear disorganization and dysfunction. Based on oxidative stress model of primary cultured stria marginal cells (MCs), we revealed that upregulated PARP1 and PAR (Poly(ADP-ribose)) polymers are responsible for MCs oxidative death with high mitochondrial permeability transition pore (mPTP) opening and mitochondrial membrane potential (MMP) collapse, while inhibition of PARP1 ameliorated the adverse outcomes. Importantly, the PARylation of apoptosis-inducing factor (AIF) is essential for its conformational change and translocation, which subsequently causes DNA break and cell death. Concretely, the interaction of PAR and truncated AIF (tAIF) is the mainstream in the parthanatos pathway. We also found that the effects of AIF cleavage and release were achieved through calpain activity and mPTP opening, both of which could be regulated by PARP1 via mediation of mitochondria Ca2+ concentration. In conclusion, the PAR-Ca2+-tAIF signaling pathway in parthanatos contributes to the oxidative stress damage observed in MCs. Targeting PAR-Ca2+-tAIF might be a potential therapeutic strategy for the early intervention of presbycusis and other oxidative stress-associated sensorineural deafness.

Quantitative profiling of cochlear synaptosomal proteins in cisplatin-induced synaptic dysfunction

The disruption of ribbon synapses in the cochlea impairs the transmission of auditory signals from the cochlear sensory receptor cells to the auditory cortex. Although cisplatin-induced loss of ribbon synapses is well-documented, and studies have reported nitration of cochlear proteins after cisplatin treatment, yet the underlying mechanism of cochlear synaptopathy is not fully understood. This study tests the hypothesis that cisplatin treatment alters the abundance of cochlear synaptosomal proteins, and selective targeting of nitrative stress prevents the associated synaptic dysfunction. Auditory brainstem responses of mice treated with cisplatin showed a reduction in amplitude and an increase in latency of wave I, indicating cisplatin-induced synaptic dysfunction. The mass spectrometry analysis of cochlear synaptosomal proteins identified 102 proteins that decreased in abundance and 249 that increased in abundance after cisplatin treatment. Pathway analysis suggested that the dysregulated proteins were involved in calcium binding, calcium ion regulation, synapses, and endocytosis pathways. Inhibition of nitrative stress by co-treatment with MnTBAP, a peroxynitrite scavenger, attenuated cisplatin-induced changes in the abundance of 27 proteins. Furthermore, MnTBAP co-treatment prevented the cisplatin-induced decrease in the amplitude and increase in the latency of wave I. Together, these findings suggest a potential role of oxidative/nitrative stress in cisplatin-induced cochlear synaptic dysfunction.

Cochlear zinc signaling dysregulation is associated with noise-induced hearing loss, and zinc chelation enhances cochlear recovery

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.

Development and Validation of an Efficient and Safe Loud Music Exposure Paradigm.

The purpose of this study was to develop a time-efficient music exposure and testing paradigm that safely creates temporary cochlear dysfunction that could be used in future temporary threshold shift (TTS) studies. A 30-min audio compilation of pop rock music tracks was created. Adult volunteers with normal hearing were then exposed to this music material monaurally through headphones for 30 min at 97 dBA or 15 min at 100 dBA. Levels were measured from the ear of a manikin and are considered to provide an equivalent daily noise dose based on a 3-dB exchange. We assessed the changes in their hearing, by means of distortion product otoacoustic emission (DPOAE) testing, and standard and extended high-frequency pure-tone audiometry before and after exposure. There were 17 volunteers in total. In the first trial, eight volunteers (four females; Mdnage = 31 years [interquartile range, IQR = 4.25]) were included. Although TTS was observed in all eight participants for at least one frequency, a large variation in affected frequencies was observed. To address this issue, the audio material was further remastered to adjust levels across the different frequency bands. Fourteen adults (nine newly recruited and five from the first trial; seven females; Mdnage = 31 years [IQR = 5]) were exposed to the new material. All but two of 17 participants presented clinically significant TTS or decrease in DPOAE amplitude in at least one frequency. Statistically significant average TTS of 7.43 dB was observed at 6 kHz. There were statistically significant average DPOAE amplitude shifts of -2.55 dB at 4 kHz, -4.97 dB at 6 kHz, and -3.14 dB at 8 kHz. No participant presented permanent threshold shift. A monaural music paradigm was developed and shown to induce statistically significant TTS and DPOAE amplitude shifts, without evidence of permanent loss. This realistic and time-efficient paradigm may be considered a viable option for experimental studies of temporary music-induced hearing loss. https://doi.org/10.23641/asha.25016471.

Maternal exposure to zinc oxide nanoparticles causes cochlear dysfunction in the offspring.

Introduction: Zinc oxide nanoparticles (ZnO NPs) have been engineered and are largely used in material science and industry. This large and increasing use justifies a careful study about the toxicity of this material for human subjects. The concerns regard also the reproductive toxicity and the fetotoxicity. Materials and methods: The effect of the exposure to ZnO NPs on the cochlear function was studied in a group of pregnant CD1 mice and in their offspring. This study is part of a larger toxicological study about the toxicity of ZnO NPs during pregnancy. Four groups were analyzed and compared, exposed and non-exposed dams and their offspring. The cochlear function was quantitatively assessed by means of Distortion Product Otoacoustic Emissions (DPOAEs). Results and discussion: A large statistically significant difference was found between the non-exposed dams offspring and the exposed dams offspring (p = 1.6 · 10-3), whose DPOAE levels were significantly lower than those of non-exposed dams offspring and comparable to those of the adults. The DPOAE levels of the exposed and non-exposed dams were very low and not significantly different. This occurrence is related to the fact that these mice encounter a rapid aging process. Conclusion: Our findings show that maternal exposure to ZnO NPs does not reflect in overt toxicity on fetal development nor impair offspring birth, however it may damage the nervous tissue of the inner ear in the offspring. Other studies should confirm this result and identify the mechanisms through which ZnO NPs may affect ear development.

Cochlear dysfunction as an early biomarker of cognitive decline in normal hearing and mild hearing loss.

Age-related hearing loss is an important risk factor for cognitive decline. However, audiogram thresholds are not good estimators of dementia risk in subjects with normal hearing or mild hearing loss. Here we propose to use distortion product otoacoustic emissions (DPOAEs) as an objective and sensitive tool to estimate the risk of cognitive decline in older adults with normal hearing or mild hearing loss. We assessed neuropsychological, brain magnetic resonance imaging, and auditory analyses on 94 subjects >64 years of age. We found that cochlear dysfunction, measured by DPOAEs-and not by conventional audiometry-was associated with Clinical Dementia Rating Sum of Boxes (CDR-SoB) classification and brain atrophy in the group with mild hearing loss (25 to 40dB) and normal hearing (<25dB). Our findings suggest that DPOAEs may be a non-invasive tool for detecting neurodegeneration and cognitive decline in the older adults, potentially allowing for early intervention.

Late-onset of Labyrinthine Dysfunction in Chronic Brucella-induced Encephalitis

Brucellosis, caused by Brucella, dominates in the Middle East. Acute or chronic brucellosis can involve any organ system, and the involvement of the central nervous system leads to encephalitis, called neurobrucellosis (NB). We report a rare case from north India where a variant of Brucella caused NB led to progressive labyrinthine dysfunction; who developed vertigo, disequilibrium, and gradual progressive sensorineural (SN) hearing loss. Audiological tests pure-tone audiometry (PTA), otoacoustic emissions (OAE), stapedial muscle reflexes, auditory evoked brainstem responses (ABR), and vestibular evoked myogenic potentials (VEMPs) were conducted on the patients. PTA showed a bilateral profound SN hearing loss, an absent OAE, and ABR suggestive of cochlear dysfunction. The cervical and ocular VEMP showed delayed n1 and p1 latencies, suggesting superior and inferior nerve branch involvement. Vertigo or disequilibrium and SN hearing loss can be the late-onset manifestations of labyrinthine dysfunction in chronic Brucella-induced encephalitis.

A retrospective review of divers treated for inner ear decompression sickness at Fiona Stanley Hospital hyperbaric medicine unit 2014-2020.

Inner ear decompression sickness (IEDCS) is increasingly recognised in recreational diving, with the inner ear particularly vulnerable to decompression sickness in divers with a right-to-left shunt, such as is possible through a persistent (patent) foramen ovale (PFO). A review of patients treated for IEDCS at Fiona Stanley Hospital Hyperbaric Medicine Unit (FSH HMU) in Western Australia was performed to examine the epidemiology, risk factors for developing this condition, the treatment administered and the outcomes of this patient population. A retrospective review of all divers treated for IEDCS from the opening of the FSH HMU on 17 November 2014 to 31 December 2020 was performed. Patients were included if presenting with vestibular or cochlear dysfunction within 24 hours of surfacing from a dive, and excluded if demonstrating features of inner ear barotrauma. There were a total of 23 IEDCS patients and 24 cases of IEDCS included for analysis, with 88% experiencing vestibular manifestations and 38% cochlear. Median dive time was 40 minutes and median maximum depth was 24.5 metres. The median time from surfacing to hyperbaric oxygen treatment (HBOT) was 22 hours. Vestibulocochlear symptoms fully resolved in 67% and complete symptom recovery was achieved in 58%. A PFO was found in 6 of 10 patients who subsequently underwent investigation with bubble contrast echocardiography upon follow-up. IEDCS occurred predominantly after non-technical repetitive air dives and ongoing symptoms and signs were often observed after HBOT. Appropriate follow-up is required given the high prevalence of PFO in these patients.

Determinants of Cochlear Dysfunction in Chronic Otitis Media: Mucosal Disease.

The nature of association between chronic otitis media (COM)-mucosal disease and sensorineural hearing loss is controversial. Identifying the risk factors which influence the bone conduction threshold in these patients can help the clinician in counselling the patients for surgery at the earliest to achieve optimum hearing outcomes. The present study was undertaken to determine the association between COM-mucosal disease and cochlear dysfunction. The study also aimed at identifying the determinants and their influence on the bone conduction thresholds of the diseased ear. In this study, 72 patients with unilateral chronic otitis media-mucosal disease were enrolled consecutively. All patients were enquired in detail about their presenting ear symptoms. All the patients underwent a pure tone audiogram in a sound treated room. Patients were categorised into two groups according to the presence of conductive hearing loss only or with a sensorineural component. The bone conduction thresholds were calculated and compared for frequencies at 0.5, 1, 2 and 4kHz. The average hearing threshold for air conduction and bone conduction were calculated across 0.5, 1 and 2kHz. Bone conduction threshold more than 20 decibels (dB) in any of the frequencies were considered significant and indicative of having sensorineural hearing loss component. The contralateral healthy ear served as control to cancel out the confounding factors such as presbyacusis, noise induced hearing loss, congenital hearing loss, etc. Multivariate linear regression models were used to evaluate the relationships between bone conduction thresholds and chronic otitis media-mucosal disease. In the present study, 18.05% of participants had a sensorineural component. The difference between the bone conduction threshold in the diseased ear and normal ear ranged from 5.41dB at 0.5kHz to 3.77dB at 4kHz (p < 0.001). Bone conduction thresholds at 4kHz were greater than that for speech frequencies (p < 0.5). 84.6% of participants with sensorineural component had a disease duration of less than 5years and the remaining 15.4% had a duration of greater than 15years. There was no statistically significant difference in the incidence of sensorineural component based on the site of the perforation (p = 0.341). 21.9% of participants who used topical antibiotic drops developed a sensorineural component, while 15% of participants who did not use antibiotic ear drop preparation developed a sensorineural component. Multivariate linear regression analysis revealed that increasing age was the only factor associated with increase in bone conduction thresholds of the diseased ear (p = 0.002). Chronic otitis media- mucosal disease appears to be associated with higher bone conduction thresholds, signifying cochlear dysfunction. A statistically significant higher bone conduction thresholds are seen across 0.5 to 4kHz in the diseased ears compared to the normal ears, signifying the vulnerability of the inner ear against chronic otitis media. In our analysis increasing age is the most significant predisposing factor associated with higher bone conduction thresholds. Higher frequencies are more affected than lower speech frequencies. Sensorineural hearing loss can occur early in the disease process and early surgical intervention in COM-mucosal disease is recommended to prevent increase in bone conduction thresholds and achieve optimum hearing outcomes.

The Effect of Alpha-Lipoic Acid in the Treatment of Chronic Subjective Tinnitus through the Tinnitus Handicap Inventory Scores.

Tinnitus affects millions of adults. Many therapies, including complementary and alternative medicine and tinnitus retraining therapies, have been trialed, but an effective option, particularly for chronic subjective tinnitus (CTS), is still lacking. This study investigated the effects of alpha-lipoic acid (600 mg. per day for two months) on two groups of patients using a questionnaire. One group (A) was affected by tinnitus associated with likely cochlear dysfunction and metabolic syndrome, and the other (B) was composed of subjects with acoustic nerve lesions. All the patients were asked to complete the Italian version of the tinnitus handicap inventory (THI) to determine the overall degree of perceived annoyance at the beginning and end of therapy. Pure tone averages for speech frequencies and for high frequencies were computed, and psychoacoustic pitch and loudness matches were determined for each subject before and after treatment. The pure tone audiometry, pitch, loudness, and THI scores of both groups were reported. In group A, statistically significant differences were observed for the "functional" and "emotional" subscales. The total score of THI and the loudness of tinnitus were also significantly reduced. No statistically significant differences were observed in group B. These findings suggest a possible contribution of the antioxidant effect to the organ of Corti in subjects with metabolic syndrome and CST.

The Stria Vascularis in Mice and Humans Is an Early Site of Age-Related Cochlear Degeneration, Macrophage Dysfunction, and Inflammation.

Age-related hearing loss, or presbyacusis, is a common degenerative disorder affecting communication and quality of life for millions of older adults. Multiple pathophysiologic manifestations, along with many cellular and molecular alterations, have been linked to presbyacusis; however, the initial events and causal factors have not been clearly established. Comparisons of the transcriptome in the lateral wall (LW) with other cochlear regions in a mouse model (of both sexes) of "normal" age-related hearing loss revealed that early pathophysiological alterations in the stria vascularis (SV) are associated with increased macrophage activation and a molecular signature indicative of inflammaging, a common form of immune dysfunction. Structure-function correlation analyses in mice across the lifespan showed that the age-dependent increase in macrophage activation in the stria vascularis is associated with a decline in auditory sensitivity. High-resolution imaging analysis of macrophage activation in middle-aged and aged mouse and human cochleas, along with transcriptomic analysis of age-dependent changes in mouse cochlear macrophage gene expression, support the hypothesis that aberrant macrophage activity is an important contributor to age-dependent strial dysfunction, cochlear pathology, and hearing loss. Thus, this study highlights the SV as a primary site of age-related cochlear degeneration and aberrant macrophage activity and dysregulation of the immune system as early indicators of age-related cochlear pathology and hearing loss. Importantly, novel new imaging methods described here now provide a means to analyze human temporal bones in a way that had not previously been feasible and thereby represent a significant new tool for otopathological evaluation.SIGNIFICANCE STATEMENT Age-related hearing loss is a common neurodegenerative disorder affecting communication and quality of life. Current interventions (primarily hearing aids and cochlear implants) offer imperfect and often unsuccessful therapeutic outcomes. Identification of early pathology and causal factors is crucial for the development of new treatments and early diagnostic tests. Here, we find that the SV, a nonsensory component of the cochlea, is an early site of structural and functional pathology in mice and humans that is characterized by aberrant immune cell activity. We also establish a new technique for evaluating cochleas from human temporal bones, an important but understudied area of research because of a lack of well-preserved human specimens and difficult tissue preparation and processing approaches.

Treatment of Tinnitus with Intratympanic Injection of Dexamethasone Versus Oral Drugs.

Tinnitus is a symptom of cochlear dysfunction, which can disturb the patient emotionally and physically. As anxiety and tinnitus persist concurrently, certain benzodiazepines have been administered as possible tinnitus treatment options. In addition to pharmacological medications, certain studies have looked at the use of vitamins to treat tinnitus. Intratympanic steroids have been successfully used in various studies as well, for the treatment of tinnitus. A clinical based interventional study was taken up among the patients visiting the ENT OPD of a State Medical College and Hospital. 160 subjects were included in the study by convenient sampling method, taking the inclusion and the exclusion criteria into consideration. Out of them, 80 subjects were given an intratympanic injection of dexamethasone and rest 80 were given oral drugs like alprazolam and vitamin B complex. Among the patients who were treated with intratympanic dexamethasone, significant improvement was seen in 36 of them, with a p value of 0.00 as compared to those who were given oral drugs, in which only 10 showed improvement, with a p value of 0.32. The improvement of the symptoms is significantly related with the duration of the symptoms in our study. Patients presenting with severe SNHL was the commonest presentation but had the least improvement (29.6%). Patients presenting within one year of occurrence of the symptoms had maximum improvement. Intratympanic dexamethasone can be considered as a good alternative for improvement of symptoms of tinnitus.

Cross-species characterization of joint otoacoustic emission profiles in sensorineural hearing loss

Current clinical assessment of otoacoustic emissions (OAEs) is typically limited to presence or absence of emissions to detect hearing loss, but recent work suggests advanced analyses and data collection methods have the potential to improve the diagnostic utility of OAEs. OAEs arise from two distinct mechanisms, nonlinear distortion and linear reflection, which are both sensitive to the health of outer hair cells but may reflect separate aspects of cochlear mechanical function. Joint distortion-reflection OAE profiles offer a non-invasive characterization of peripheral auditory physiology and dysfunction (Abdala and Kalluri, 2017). In this study, swept-tone distortion-product OAEs were separated into distortion and reflection components. Swept-tone stimulus-frequency OAEs, reflection-type emissions, were measured using a suppressor paradigm. Joint OAE profiles will be estimated for multiple pre-clinical chinchilla models of sensorineural hearing loss (SNHL) and in humans with either normal hearing or sensorineural hearing loss. In chinchillas, we expect SNHL models with distinct profiles of cochlear damage to yield separable joint OAE profiles. Findings in chinchillas will provide mechanistic insight into OAE profile clusters in humans. These data test the sensitivity of joint OAE profiles to specific cochlear dysfunctions and contribute to development of precision diagnostics for SNHL.

Jackson Heart Study: Aggregate cardiovascular disease risk and auditory profiles.

Evaluate the relationship between cardiovascular disease (CVD) risk factors and cochlear function in African Americans. Relationships between hearing loss, cochlear function, and CVD risk factors were assessed in a cross-sectional analysis of 1106 Jackson Heart Study participants. Hearing loss was defined as puretone average (PTA0.5,1,2,4) > 15 dB HL. Distortion product otoacoustic emissions (DPOAEs) were collected for f 2=1.0-8.0kHz. Two amplitude averages were computed: DPOAElow (f 2 ≤ 4kHz) and DPOAEhigh (f 2 ≥ 6kHz). Based on major CVD risk factors (diabetes, current smoking, total cholesterol ≥240 mg/dL or treatment, and systolic blood pressure [BP]/diastolic BP ≥ 140/≥90 mmHg or treatment), four risk groups were created: 0, 1, 2, and ≥3 risk factors. Logistic regression estimated the odds of hearing loss and absent/reduced DPOAElow and DPOAEhigh by CVD risk status adjusting for age, sex, education, BMI, vertigo, and noise exposure. With multivariable adjustment, diabetes was associated with hearing loss (OR=1.48 [95% CI: 1.04-2.10]). However, there was not a statistically significant relationship between CVD risk factors (individually or for overall risk) and DPOAEs. Diabetes was associated with hearing loss. Neither individual CVD risk factors nor overall risk showed a relationship to cochlear dysfunction. 2b.

Noise-induced auditory damage affects hippocampus causing memory deficits in a model of early age-related hearing loss

Several studies identified noise-induced hearing loss (NIHL) as a risk factor for sensory aging and cognitive decline processes, including neurodegenerative diseases, such as dementia and age-related hearing loss (ARHL). Although the association between noise- and age-induced hearing impairment has been widely documented by epidemiological and experimental studies, the molecular mechanisms underlying this association are not fully understood as it is not known how these risk factors (aging and noise) can interact, affecting memory processes. We recently found that early noise exposure in an established animal model of ARHL (C57BL/6 mice) accelerates the onset of age-related cochlear dysfunctions. Here, we extended our previous data by investigating what happens in central brain structures (auditory cortex and hippocampus), to assess the relationship between hearing and memory impairment and the possible combined effect of noise and sensory aging on the cognitive domain. To this aim, we exposed juvenile C57BL/6 mice of 2 months of age to repeated noise sessions (60 min/day, pure tone of 100 dB SPL, 10 kHz, 10 consecutive days) and we monitored auditory threshold by measuring auditory brainstem responses (ABR), spatial working memory, by using the Y-maze test, and basal synaptic transmission by using ex vivo electrophysiological recordings, at different time points (1, 4 and 7 months after the onset of noise exposure, corresponding to 3, 6 and 9 months of age). We found that hearing loss, along with accelerated presbycusis onset, can induce persistent synaptic alterations in the auditory cortex. This was associated with decreased memory performance and oxidative-inflammatory injury in the hippocampus, the extra-auditory structure involved in memory processes. Collectively, our data confirm the critical relationship between auditory and memory circuits, suggesting that the combined detrimental effect of noise and sensory aging on hearing function can be considered a high-risk factor for both sensory and cognitive degenerative processes, given that early noise exposure accelerates presbycusis phenotype and induces hippocampal-dependent memory dysfunctions.

Effects of Ndufs4 Deletion on Hearing after Various Acoustic Exposures.

Mitochondrial dysfunction can cause cochlear dysfunction and accelerate noise-induced hearing loss (NIHL). NADH dehydrogenase (ubiquinone) Fe-S protein 4 (Ndufs4) is one of the subunits of mitochondrial complex I and has a role in the assembly and stabilization of complex I. However, the involvement of Ndufs4 in the pathogenesis of NIHL has not been reported. The aim of this study was to evaluate whether Ndufs4 deletion causes vulnerability to noise exposures. The wild-type (WT) and Ndufs4 knockout (KO) mice with C57BL/6J genetic background were used. Cochlear histology and hearing thresholds were assessed after noise exposure at 100 or 86 dB sound pressure level (SPL). Immunostaining showed the widespread expression of Ndufs4 in the cochlea. After noise exposure at 100 dB SPL, auditory brainstem response (ABR) threshold shifts at 4 kHz in Ndufs4 KO mice were significantly higher than that in WT mice. After noise exposure at 86 dB SPL, ABR threshold shifts, wave 1 amplitudes, and the number of synapses in the inner hair cells were not significantly different. RNA sequencing revealed the decreased expression of energy generation-related genes inNdufs4 KO mice. Ndufs4 deficiency accelerates permanent low-frequency threshold shifts after moderate noise exposure.