scholarly journals Regulator of G Protein Signalling 4 (RGS4) as a Novel Target for the Treatment of Sensorineural Hearing Loss

2020 ◽  
Vol 22 (1) ◽  
pp. 3
Author(s):  
Christine Fok ◽  
Milan Bogosanovic ◽  
Madhavi Pandya ◽  
Ravindra Telang ◽  
Peter R. Thorne ◽  
...  

We and others have previously identified signalling pathways associated with the adenosine A1 receptor (A1R) as important regulators of cellular responses to injury in the cochlea. We have shown that the “post-exposure” treatment with adenosine A1R agonists confers partial protection against acoustic trauma and other forms of sensorineural hearing loss (SNHL). The aim of this study was to determine if increasing A1R responsiveness to endogenous adenosine would have the same otoprotective effect. This was achieved by pharmacological targeting of the Regulator of G protein Signalling 4 (RGS4). RGS proteins inhibit signal transduction pathways initiated by G protein-coupled receptors (GPCR) by enhancing GPCR deactivation and receptor desensitisation. A molecular complex between RGS4 and neurabin, an intracellular scaffolding protein expressed in neural and cochlear tissues, is the key negative regulator of A1R activity in the brain. In this study, Wistar rats (6–8 weeks) were exposed to traumatic noise (110 dBSPL, 8–16 kHz) for 2 h and a small molecule RGS4 inhibitor CCG-4986 was delivered intratympanically in a Poloxamer-407 gel formulation for sustained drug release 24 or 48 h after noise exposure. Intratympanic administration of CCG-4986 48 h after noise exposure attenuated noise-induced permanent auditory threshold shifts by up to 19 dB, whilst the earlier drug administration (24 h) led to even better preservation of auditory thresholds (up to 32 dB). Significant improvement of auditory thresholds and suprathreshold responses was linked to improved survival of sensorineural tissues and afferent synapses in the cochlea. Our studies thus demonstrate that intratympanic administration of CCG-4986 can rescue cochlear injury and hearing loss induced by acoustic overexposure. This research represents a novel paradigm for the treatment of various forms of SNHL based on regulation of GPCR.

2020 ◽  
Vol 12 (1) ◽  
pp. 59
Author(s):  
Diana Kusuma Wardhani ◽  
Jojok Mukono Mukono

Introduction: As one of the preferred modes of land transportation, the frequency of train services was very high. One of the negative impacts arising from train activity was noise. The high noise intensity of the train causes hearing loss. Method: This study aims to analyze the differences in the incidence of hearing loss in 2 groups of residents in Turirejo Lawang Malang. This research used the observational method and the data were analyzed descriptive qualitative. A total of 20 people were selected as respondents by purposive sampling. Noise intensity was measured by Sound Level Meter and audiometric measurements were examined at SIMA Malang Laboratory. Result and Discussion: The prevalence of sensorineural hearing loss was more common in residents whose homes at 3-7 m away from the railroad tracks. In addition, residents who lived at least 15 years at a distance of 3-7 m also experienced more hearing loss. One cause of hearing loss is due to exposure to high noise and for a long time and will damage the hair cells in the cochlea, causing hearing loss. If noise exposure continues and for a long period of time damage to hair cells will be permanent and cannot return to normal. Conclusion: There needs to be a policy from the government in determining the minimum limit of the distance of the house to the railroad tracks. In addition, it is necessary to install a barrier near people’s homes to reduce noise.


2015 ◽  
Vol 273 (5) ◽  
pp. 1099-1105 ◽  
Author(s):  
Lisa Aarhus ◽  
Kristian Tambs ◽  
Per Nafstad ◽  
Eskil Bjørgan ◽  
Bo Engdahl

Revista CEFAC ◽  
2017 ◽  
Vol 19 (6) ◽  
pp. 764-772 ◽  
Author(s):  
Gregorina Silva Ribeiro Rocha ◽  
Marlizete Maldonado Vargas ◽  
Margarete Zanardo Gomes

ABSTRACT Purpose: to evaluate the perception of the level of quality of life in subjects with tinnitus, with and without hearing loss. Methods: a cross-sectional quantitative study. A total of 189 subjects (mean age 53.06 years) divided into four groups. Group 1: subjects with normal auditory thresholds without tinnitus complaint; Group 2: subjects with normal auditory thresholds and tinnitus complaint; Group 3: subjects with sensorineural hearing loss without tinnitus complaint; Group 4: subjects with sensorineural hearing loss and with tinnitus complaint. Levels of quality of life were investigated through the World Health Organization Quality Of Life (WHOQOL) website - brief and psycho-emotional and functional aspects of patients with tinnitus through the Tinnitus Handicap Inventory (THI). Statistical analyzes, comparisons among groups and descriptive analysis were performed, considering a significance level of 5%. Results: the overall mean scores of quality of life in group 4 (56.07) were smaller than those of group 1 (64.67) (p<0.05). The subjects with tinnitus complaint presented a moderate level of disturbance of the symptom. Conclusion: tinnitus interferes in the quality of life of individuals who had preserved or altered auditory thresholds. Therefore, means to reduce the discomfort caused by tinnitus symptom should be developed, in order to improve patients' quality of life.


2020 ◽  
pp. 1-15
Author(s):  
Garrett Cardon ◽  
Anu Sharma

Purpose Auditory threshold estimation using the auditory brainstem response or auditory steady state response is limited in some populations (e.g., individuals with auditory neuropathy spectrum disorder [ANSD] or those who have difficulty remaining still during testing and cannot tolerate general anesthetic). However, cortical auditory evoked potentials (CAEPs) can be recorded in many such patients and have been employed in threshold approximation. Thus, we studied CAEP estimates of auditory thresholds in participants with normal hearing, sensorineural hearing loss, and ANSD. Method We recorded CAEPs at varying intensity levels to speech (i.e., /ba/) and tones (i.e., 1 kHz) to estimate auditory thresholds in normal-hearing adults ( n = 10) and children ( n = 10) and case studies of children with sensorineural hearing loss and ANSD. Results Results showed a pattern of CAEP amplitude decrease and latency increase as stimulus intensities declined until waveform components disappeared near auditory threshold levels. Overall, CAEP thresholds were within 10 dB HL of behavioral thresholds for both stimuli. Conclusions The above findings suggest that CAEPs may be clinically useful in estimating auditory threshold in populations for whom such a method does not currently exist. Physiologic threshold estimation in difficult-to-test clinical populations could lead to earlier intervention and improved outcomes.


2021 ◽  
Vol 15 ◽  
Author(s):  
Lingna Guo ◽  
Wei Cao ◽  
Yuguang Niu ◽  
Shuangba He ◽  
Renjie Chai ◽  
...  

Inner ear hair cells (HCs) and spiral ganglion neurons (SGNs) are the core components of the auditory system. However, they are vulnerable to genetic defects, noise exposure, ototoxic drugs and aging, and loss or damage of HCs and SGNs results in permanent hearing loss due to their limited capacity for spontaneous regeneration in mammals. Many efforts have been made to combat hearing loss including cochlear implants, HC regeneration, gene therapy, and antioxidant drugs. Here we review the role of autophagy in sensorineural hearing loss and the potential targets related to autophagy for the treatment of hearing loss.


CoDAS ◽  
2013 ◽  
Vol 25 (3) ◽  
pp. 224-228 ◽  
Author(s):  
Kelly Martins ◽  
Marília Fontenele ◽  
Silva Câmara ◽  
Edi Lúcia Sartorato

PURPOSE: This study aimed to correlate probable predisposing factors for sensorineural hearing loss in elderly by investigating the audiologic characteristics and frequency of mutations in genes considered responsible for non-syndromic hearing loss. METHODS: Sixty elderly patients were separated into two groups: the Case Group, composed of 30 individuals, 21 females and nine males, all 60 years old or older and presenting diagnoses of sensorineural hearing loss, and the Control Group, composed of 30 elderly individuals matched to the experimental group by age and gender, presenting normal hearing. The patients underwent anamnesis and pure tone audiometry in frequencies of 250, 500, 1000, 2000, 3000, 4000 and 6000 Hz. Blood samples were collected from each patient for analysis of mutations in nuclear and mitochondrial genes related to non-syndromic sensorineural hearing loss. RESULTS: It was observed a greater tendency to noise exposure and consumption of alcohol in the Case Group. The statistically significant symptoms between the groups were tinnitus and hearing difficulty in several situations as: silent environment, telephone, television, sound location and in church. All the individuals of Case Group presented sensorineural and bilateral hearing loss. The symmetry and progression of the hearing impairment were also statistically significant between the groups. No genetic mutations were identified. CONCLUSION: The most reported symptoms were communication difficulties and tinnitus. The predominant auditory characteristics included sensorineural, bilateral, progressive and symmetrical hearing loss. It was not evidenced a relationship between sensorineural hearing loss in elderly and genes considered responsible for non-syndromic hearing loss as no genetic mutation was found in this study.


Author(s):  
V. B. Pankova ◽  
M. F. Vilk ◽  
N. A. Daikhes

Modern, problematic issues of prevalence, structure and high rates of hearing loss from exposure to industrial noise in the form of clinical stages of chronic sensorineural hearing loss are reflected. The possibility of harmonization of the List of occupational diseases of the ICD 10th and 11th reviews in hearing impairment is discussed


2012 ◽  
Vol 3 (3) ◽  
pp. 127-132 ◽  
Author(s):  
Mustafa Paksoy ◽  
Arif Sanli ◽  
Umit Hardal ◽  
Sermin Kibar ◽  
Gokhan Altin ◽  
...  

ABSTRACT Objective In otology, a wide variety of devices are used that have significant noise output, both operated ear and the patient. We aimed to determine hearing damages due to drill-generated acoustic trauma in ear surgery. We want to find how degree drill-generated acoustic trauma is responsible from sensorineural hearing loss in ear surgery. Materials and methods We designed a retrospective study about 100 patients who underwent radical or modiphied radical mastoidectomy and tympanoplasty. The audiometric testing was done both pre and postoperatively to detect any significant hearing loss in the immediate postoperative period. The data were analyzed using the Wilcoxon sign and Mann-Whitney U tests. This study proposes that hearing loss is caused by drill noise conducted to the operated ear by vibrations of temporal bone. Results A sensorineural hearing loss soon after mastoid surgery is seen due to the noise generated by the drill. Mean pure-tone thresholds obtained was significantly more in mastoidectomy applied patients when compared to tympanoplasty . Mean bone conduction (BC) hearing levels impaired 6,6 dB in 1 kHz, 5.5 dB in 0.5 kHz, 5 dB in 4.kHz and 3.1 dB in 2 kHz in mastoidectomy groups but improved 5.5 dB in 0.5 kHz, 2.2 dB in 1 kHz, 2.7 dB in 2 kHz in tympanoplasty groups. Statistically significant differences were observed at the 0.5-1 and 4 kHz frequencies pre and postoperative in the hearing thresholds of BC changing in mastoidectomy group, however, the averages of ranks of all pre and postoperative measurement of hearing levels show differences between mastoidectomy and tympanoplasty groups was significant in statistically at independent groups (p < 0.05). Conclusion We conclude that drill-generated noise during mastoid surgery has been incriminated as a cause of sensorineural hearing loss. Drilling during mastoid surgery may result in temporary or permanent noise-induced hearing loss. Possible noise disturbance to the inner ear can only be avoided by minimizing the duration of harmful noise exposure and carefull using burr to near the cochlear structures. How to cite this article Paksoy M, Sanli A, Hardal U, Kibar S, Altin G, Erdogan BA, Bekmez ZE. How Drill-Generated Acoustic Trauma effects Hearing Functions in an Ear Surgery? Int J Head and Neck Surg 2012;3(3):127-132.


2019 ◽  
Author(s):  
Viacheslav Vasilkov ◽  
Sarah Verhulst

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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