Role of Free Radicals, Glutamate Toxicity, Glutathione Depletion in Apoptosis of Cochlear Hair Cells, Neuronal Cells among Patients with Sensorineural Hearing Loss

Abstract Introduction Hearing loss may lead to depression, decreased quality of life, reduced functional status and social isolation. The glutathione-S transferase (GSTS) is an antioxidant scavenging enzyme. Decreased glutathione and GSTS activity levels lead to an increase in susceptibility of hair-cell damage leading to sensorineural hearing loss. The cumulative effect of oxidative stress and mitochondrial damage by free radicals results in the mutation/deletion of deoxyribonucleic acid, leading to decline in mitochondrial function, which in turn plays an important role in inducing apoptosis of the cochlear cells. Other risk factors also include noise exposure, genetic predisposition, health comorbidities, ototoxic drugs, infections, and immune-mediated inflammation of auditory cells. Study Design Prospective, non-comparative, metacentric clinical study. Materials and Methods The study was carried out in 30 patients from 6/5/2016 to 10/1/2018. Total of 30 patients of sensorineural hearing loss were enrolled (17 males, 13 females). Clinical history, ENT examination, and audiogram were done, treatment duration of 8 weeks for each patient and followed up to 3 outpatient visits. The patient was administered rebamipide 100 mg, alpha lipoic acid 100 mg, and acetylcysteine 100 mg capsules twice a day for a total period of 8 weeks. Wherever giddiness was an added symptom, Cinnarizine 20mg with Diaminehydrate 40 mg combination twice a day was added up to complete relief of symptoms, thereafter once a day as maintenance dose over a period of 8 weeks. Wherever tinnitus was an added symptom, deflazacort 6 mg twice a day was added and tapered up to 1 month. If the symptom of tinnitus persisted, intratympanic steroid injection was given. During every visit, clinical assessment and audiogram were repeated. Results Our study demonstrated greater improvement in hearing at higher frequencies with 8 weeks of rebamipide 100 mg + alpha lipoic acid 100 mg + acetylcysteine 100 mg administration in 30 patients with twice-daily dosing. Conclusion Synthesis of free radicals in the inner ear may play an important part in the pathogenesis of sensory hearing loss. The combination of rebamipide 100 mg + alpha lipoic acid 100 mg + acetylcysteine 100 mg is effective prophylaxis in sensorineural hearing loss that addresses both factors of inhibiting the cochlear cell damage and enhancing cochlear cell preservation.

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Enhancing the sensitivity of the envelope-following response for cochlear synaptopathy screening in humans: the role of stimulus envelope

10.1101/2020.06.05.136184 ◽

2020 ◽

Cited By ~ 2

Author(s):

Viacheslav Vasilkov ◽

Markus Garrett ◽

Manfred Mauermann ◽

Sarah Verhulst

Keyword(s):

Hearing Loss ◽

Hair Cell ◽

Sensorineural Hearing Loss ◽

Auditory Nerve ◽

Outer Hair Cell ◽

Cell Damage ◽

Modulation Depth ◽

Auditory Evoked Potential ◽

Sensorineural Hearing ◽

Age Related

AbstractAuditory de-afferentation, a permanent reduction in the number of innerhair-cells and auditory-nerve synapses due to cochlear damage or synaptopathy, can reliably be quantified using temporal bone histology and immunostaining. However, there is an urgent need for non-invasive markers of synaptopathy to study its perceptual consequences in live humans and to develop effective therapeutic interventions. While animal studies have identified candidate auditory-evoked-potential (AEP) markers for synaptopathy, their interpretation in humans has suffered from translational issues related to neural generator differences, unknown hearing-damage histopathologies or lack of measurement sensitivity. To render AEP-based markers of synaptopathy more sensitive and differential to the synaptopathy aspect of sensorineural hearing loss, we followed a combined computational and experimental approach. Starting from the known characteristics of auditory-nerve physiology, we optimized the stimulus envelope to stimulate the available auditory-nerve population optimally and synchronously to generate strong envelope-following-responses (EFRs). We further used model simulations to explore which stimuli evoked a response that was sensitive to synaptopathy, while being maximally insensitive to possible co-existing outer-hair-cell pathologies. We compared the model-predicted trends to AEPs recorded in younger and older listeners (N=44, 24f) who had normal or impaired audiograms with suspected age-related synaptopathy in the older cohort. We conclude that optimal stimulation paradigms for EFR-based quantification of synaptopathy should have sharply rising envelope shapes, a minimal plateau duration of 1.7-2.1 ms for a 120-Hz modulation rate, and inter-peak intervals which contain near-zero amplitudes. From our recordings, the optimal EFR-evoking stimulus had a rectangular envelope shape with a 25% duty cycle and a 95% modulation depth. Older listeners with normal or impaired audiometric thresholds showed significantly reduced EFRs, which were consistent with how (age-induced) synaptopathy affected these responses in the model.Significance StatementCochlear synaptopathy was in 2009 identified as a new form of sensorineural hearing loss (SNHL) that also affects primates and humans. However, clinical practice does not routinely screen for synaptopathy, and hence its consequences for degraded sound and speech perception remain unclear. Cochlear synaptopathy may thus remain undiagnosed and untreated in the aging population who often report self-reported hearing difficulties. To enable an EEG-based differential diagnosis of synaptopathy in humans, it is crucial to develop a recording method that evokes a robust response and emphasizes inter-individual differences. These differences should reflect the synaptopathy aspect of SNHL, while being insensitive to other aspects of SNHL (e.g. outer-hair-cell damage). This study uniquely combines computational modeling with experiments in normal and hearing-impaired listeners to design an EFR stimulation and recording paradigm that can be used for the diagnosis of synaptopathy in humans.

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Towards a differential diagnosis of cochlear synaptopathy and outer-hair-cell deficits in mixed sensorineural hearing loss pathologies

10.1101/19008680 ◽

2019 ◽

Cited By ~ 6

Author(s):

Viacheslav Vasilkov ◽

Sarah Verhulst

Keyword(s):

Hearing Loss ◽

Differential Diagnosis ◽

Hair Cell ◽

Sensorineural Hearing Loss ◽

Noise Exposure ◽

Outer Hair Cell ◽

Cell Damage ◽

Sensorineural Hearing ◽

Inner Hair Cell ◽

Hearing Thresholds

AbstractDamage to the auditory periphery is more widespread than predicted by the gold-standard clinical audiogram. Noise exposure, ototoxicity and aging can destroy cochlear inner-hair-cell afferent synapses and result in a degraded subcortical representation of sound while leaving hearing thresholds unaffected. Damaged afferent synapses, i.e. cochlear synaptopathy, can be quantified using histology, but a differential diagnosis in living humans is difficult: histology cannot be applied and existing auditory evoked potential (AEP) metrics for synaptopathy become insensitive when other sensorineural hearing impairments co-exist (e.g., outer-hair-cell damage associated with elevated hearing thresholds). To develop a non-invasive diagnostic method which quantifies synaptopathy in humans and animals with normal or elevated hearing thresholds, we employ a computational model approach in combination with human AEP and psychoacoustics. We propose the use of a sensorineural hearing loss (SNHL) map which comprises two relative AEP-based metrics to quantify the respective degrees of synaptopathy and OHC damage and evaluate to which degree our predictions of AEP alterations can explain individual data-points in recorded SNHL maps from male and female listeners with normal or elevated audiometric thresholds. We conclude that SNHL maps can offer a more precise diagnostic tool than existing AEP methods for individual assessment of the synaptopathy and OHC-damage aspect of sensorineural hearing loss.Significance StatementHearing loss ranks fourth in global causes for disability and risk factors include noise exposure, ototoxicity and aging. The most vulnerable parts of the cochlea are the inner-hair-cell afferent synapses and their damage (cochlear synaptopathy) results in a degraded subcortical representation of sound. While synaptopathy can be estimated reliably using histology, it cannot be quantified this way in living humans. Secondly, other co-existing sensorineural hearing deficits (e.g., outer-hair-cell damage) can complicate a differential diagnosis. To quantify synaptopathy in humans and animals with normal or elevated hearing thresholds, we adopt a theoretical and interdisciplinary approach. Sensitive diagnostic metrics for synaptopathy are crucial to assess its prevalence in humans, study its impact on sound perception and yield effective hearing restoration strategies.

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Hearing Loss Associated with Xylene Exposure in a Laboratory Worker

Journal of the American Academy of Audiology ◽

10.3766/jaaa.23.10.7 ◽

2012 ◽

Vol 23 (10) ◽

pp. 824-830 ◽

Cited By ~ 3

Author(s):

Adrian Fuente ◽

Bradley McPherson ◽

Linda J. Hood

Keyword(s):

Hearing Loss ◽

Sensorineural Hearing Loss ◽

Otoacoustic Emissions ◽

Outer Hair Cell ◽

Cell Damage ◽

Auditory Brainstem ◽

Sensorineural Hearing ◽

Auditory Brainstem Responses ◽

Initial Assessment ◽

Laboratory Worker

Background: Xylene is an organic solvent, widely used in histology laboratories and other occupational settings. Research in animals has demonstrated that xylene induces outer hair cell damage. Evidence regarding the effects of xylene in humans is only available from studies investigating workers exposed to mixtures of solvents containing xylene. These data indicate that mixtures of solvents containing xylene may induce hearing loss and central auditory dysfunction. Purpose: To comprehensively evaluate the peripheral and central auditory system of a histology laboratory worker exposed to xylene, who had presented with bilateral mild sensorineural hearing loss at an initial assessment. Research Design: A case report of a male histology laboratory worker who has been exposed to xylene for over 20 yr. Results: A diagnosis of bilateral mild sensorineural hearing loss of cochlear origin was made on the basis of otological, neuroimaging, and audiological examinations. Results indicating the absence of transient-evoked otoacoustic emissions, and auditory brainstem responses as expected for a mild cochlear hearing loss, were obtained. Conclusions: The observed bilateral mild sensorineural hearing loss was considered to have been induced by xylene exposure, due to the absence of any other etiological factors related to the onset of hearing loss. The results found in this patient are in agreement with animal data indicating xylene-induced ototoxicity. Xylene-exposed individuals should be audiologically monitored on a regular basis.

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