Treatment Of Sensorineural Hearing Loss Research Articles

The Vibrant Soundbridge as an active implant in middle ear surgery

Implantable hearing aids are not only gaining importance for the treatment of sensorineural hearing loss, but also for treatment of mixed hearing loss. The most frequently used active middle ear implant is the Vibrant Soundbridge (VSB) system (Fa. MED-EL, Innsbruck, Österrreich). Following widening of the spectrum of indications for the VBS, various new coupling systems have been established. Based on the literature, available petrosal bone investigations and finite element model (FEM) calculations, this article summarizes the current knowledge concerning mechanical excitation by the VSB. Important concomitant aspects related to coupling, transmission and measurement are also discussed.

PRIEŪMINIO IDIOPATINIO NEUROSENSORINIO KLAUSOS PAŽEIDIMO PROGNOSTINIAI VEIKSNIAI

Objectives. We investigated prognostic factors in sudden sensorineural hearing loss.Patients and methods. Patients were recruited into the trial between August 2011 and June 2013 with complains : an abrupt onset of more than 30 dB hearing loss at three consecutive frequencies during period 72 hours, unilateral. 202 patients were randomized to 1 of 2 groups and administered treatment. Group I : patients were given 12 capsules (60 mg) of prednisolon for 7 days, then 2 less capsule per two days until finished. Group II : patients were given systemic prednisolon and additionally, three times a week were administered a transtympanic injection 1,0 ml - 4 mg/ml dexamethasone solution. Audiograms were performed at first visit and 30 days after treatment. Pure tone averages (PTAs) were measured by taking the 6-frequency average of the threshold value at 250, 500, 1,000, 2,000, 4,000 and 8,000 Hz.Results. Our analysis suggests the presence of the following82prognostic factors for sudden sensorineural hearing loss : method of sudden sensorineural hearing loss treatment (better results in combined treatment group); time delay before start of treatment (better results when treatment started within 2 days of the first symptoms of SSNHL); age; seasonal occurrence of the disease in the winter and spring; stress condition, viral infection and trauma(acoustic) before SSNHL, tinnitus, fullness of the ear.Conclusions. Method of sudden sensorineural hearing loss treatment (better results in combined treatment group); time delay before start of treatment ( better results when treatment started within 2 days of the first symptoms of SSNHL); age; seasonal occurrence of the disease in the winter and spring; stress condition, viral infection and trauma (acoustic) before SSNHL, tinnitus, fullness of the ear are prognostic factors for hearing recovery in SSNHL. Gender, proffesional skills, smoking habits, otological and family history, osteochondrosis are not confirmed as prognostic factors for hearing recovery in SSNHL in our study. Knowing of prognostic factors for hearing recovery in SSNHL leads as predict course of the illness and proper prognosis for hearing improvement.

Improvement in Sensorineural Hearing Loss During Pregnancy

Hearing loss is known to occur in some pregnant women, but improvement in sensorineural thresholds has not been audiometrically characterized. Here, we describe a patient with a history of Ménière's disease and vestibular migraine who experienced temporary recovery of her hearing during pregnancy. Audiograms were obtained from a 31-year-old female over the course of 2 successive pregnancies. Audiograms revealed a substantial improvement in hearing by the third trimester during each pregnancy, with a rapid return to baseline thresholds after delivery. This case is unique in documenting improvements in hearing thresholds during pregnancy and substantiates the effects of hormonal changes on hearing thresholds in humans. It raises the intriguing possibility of hormonal therapy as a treatment for sensorineural hearing loss in specific clinical situations.

Exogenous BDNF and Chondroitinase ABC Consisted Biomimetic Microenvironment Regulates Survival, Migration and Differentiation of Human Neural Progenitor Cells Transplanted into a Rat Auditory Nerve

Current putative regeneration oriented studies express possible role of stem cell based implantation strategy in the restoration of fundamental perception of hearing. The present work utilizes a rat auditory nerve (AN) directed transplantation of human neural progenitor cells (HNPCs) as a cell replacement therapy for impaired auditory function. Groups of b-bungarotoxin induced auditory function compromised female rats were used to transplant HNPCs in the nerve trunk. In the treatment groups, brain derived neurotrophic factor (BDNF), peptide amphiphile nanofiber bioactive gel (Bgel) and Chondroitinase ABC (ChABC), a digestive enzyme that cleaves the core of chondroitin sulphate proteoglycans, were added along with HNPCs while the control groups were with PA inert gel (Igel) and devoid of ChABC. Six weeks post transplantation survival, migration, and differentiation of HNPCs were studied and compared. The groups treated with BDNF and Bgel showed improved survival and differentiation of transplanted HNPCs while the ChABC treated group showed significant migration of HNPCs along the AN and elongation of neuronal fibers along the nerve towards the cochlear nucleus (CN) which was characterized by immunocytochemical markers for human Nuclei (HuN), human mitochondria (HuM) and neuronal β-tubulin (Tuj1). These findings show that addition of BDNF and ChABC consisted Bgel environment facilitated HNPC survival, migration and differentiation along the transplanted rat AN towards the CN. This transplantation strategy provides unique experimental validation for futuristic role of cell based biomaterial consisted neurotrophic factor application in clinically transferable treatment of sensorineural hearing loss (SNHL) along with cochlear implants (CI).

Insulin-like growth factor 1 inhibits hair cell apoptosis and promotes the cell cycle of supporting cells by activating different downstream cascades after pharmacological hair cell injury in neonatal mice

Sensorineural hearing loss, which is mainly caused by cochlear hair cell damage, is an intractable disease, as cochlear hair cells and supporting cells are unable to proliferate in postnatal mammals. As a novel and potent treatment for sensorineural hearing loss, we have studied IGF-1 and found that it protects cochlear hair cells from the damage caused by noise and ischemic trauma. Through a clinical trial, we have also confirmed that IGF-1 is an effective treatment for idiopathic sudden sensorineural hearing loss. In the current study, we attempted to identify the downstream pathways of the IGF-1 signal and the mechanisms by which IGF-1 protects the neonatal mouse cochlear hair cells that have been damaged by neomycin. IGF-1 activated both the PI3K/Akt and MEK/ERK pathways to maintain the hair cell numbers in the injured cochlea. The PI3K/Akt pathway specifically protected the cochlear inner hair cells through the inhibition of apoptosis. In contrast, the MEK/ERK pathway induced the cell cycle promotion of Hensen's and Claudius' cells, the supporting cells that are located lateral to the outer hair cells of the cochlea. This cell cycle promotion of the supporting cells resulted in the maintenance of the outer hair cell numbers. These results indicate that IGF-1 is a growth factor that efficiently regulates different mechanisms through different downstream cascades, thereby protecting cochlear hair cells.

Stem cell transplantation via the cochlear lateral wall for replacement of degenerated spiral ganglion neurons

Spiral ganglion neurons (SGNs) are poorly regenerated in the mammalian inner ear. Because of this, stem cell transplantation has been used to replace injured SGNs, and several studies have addressed this approach. However, the difficulty of delivering stem cells into the cochlea and encouraging their migration to Rosenthal's canal (RC), where the SGNs are located, severely restricts this therapeutic strategy. In this study, we attempted to establish a new stem cell transplantation route into the cochlea via the cochlear lateral wall (CLW). First, we tested the precision of this route by injecting Fluorogold into the CLW and next assessed its safety by mock surgeries. Then, using a degenerated SGN animal model, we transplanted neural stem cells (NSCs), derived from the olfactory bulb of C57BL/6-green fluorescent protein (GFP) mice, via the CLW route and examined the cells' distribution in the cochlea. We found the CLW transplantation route is precise and safe. In addition, NSCs migrated into RC with a high efficiency and differentiated into neurons in a degenerated SGN rat model after the CLW transplantation. This result revealed that the basilar membrane (BM) may have crevices permitting the migration of NSCs. The result of this study demonstrates a novel route for cell transplantation to the inner ear, which is important for the replacement of degenerated SGNs and may contribute to the treatment of sensorineural hearing loss.

Third-Generation Bisphosphonates for Treatment of Sensorineural Hearing Loss in Otosclerosis

To evaluate hearing outcomes in patients treated with third generation bisphosphonates for otosclerosis-related sensorineural hearing loss (SNHL). Otosclerosis is a disease of abnormal bone remodeling in the otic capsule. In recent years, third generation bisphosphonates, with more powerful anti-resorptive properties and increased bone affinity, have demonstrated effectiveness in the treatment of osteoporosis and other metabolic bone diseases. We hypothesized that newer generation bisphosphonates, such as risedronate and zoledronate, would be effective in slowing the progression of SNHL in patients with otosclerosis. Retrospective review. Tertiary referral center, ambulatory care. Risedronate or zoledronate administration. Bone conduction pure tone threshold averages (PTAs) and word recognition (WR) scores were examined for each ear before and after bisphosphonate treatment. Criteria for significant change were defined as greater than 10 decibels in PTA or between 4% and 18% in WR based on binomial variance. All 10 patients had audiometric progression of SNHL in the pretreatment monitoring interval and 12 ears met criteria for significant progression. All 10 patients (19 ears) showed at least no significant progression of SNHL (i.e., stabilization) at an average follow-up of 13 months. Two patients (3 ears) showed improvement by defined audiometric criteria. There were no major complications. Treatment with zoledronate or risedronate stabilized progressive SNHL related to otosclerosis in this small group of patients. Further evaluation of third-generation bisphosphonate treatments is warranted.

Mining Immune Epitopes in Ménière’s Disease and Sudden Sensorineural Hearing Loss

Objective: Etiologies for Ménière’s disease and sudden sensorineural hearing loss remain unknown. Indirect evidence exists for allergy-mediated or autoimmune process. The purpose of this study is to determine whether immunogenic proteins share similar sequences with inner ear proteins, which may lead to cross-reactivity and immune activation in inner ear disorders. Method: Comprehensive bioinformatic primary sequence analyses of intact and mutated proteins associated with human syndromic and nonsyndromic hearing loss and proteins expressed in the human inner ear was performed. Comparison of sequences to epitopes in the Immune Epitope Database was performed by exact match, BLAST, and BLOSUM62 score computational algorithms. Results: Computational analysis of primary protein sequence for 81 known inner ear proteins, 102 proteins from genes identified in syndromic and non-syndromic hearing loss, and 438 protein sequences with known mutations that contribute to sensorineural hearing loss was compared to 151,086 epitopes previously implicated in allergic, autoimmune, and infectious disorders within the Immune Epitope Database. The exact match and BLAST algorithms identified 1925 and 97 unique epitope matches, respectively. Top BLOSUM62 score algorithm resulted in a single hit for the 47 kDa membrane antigen. Other epitopes included those seen in allergic rhinitis, infectious diseases, and autoimmune disorders. Conclusion: Abnormal immune activation is suspected in Ménière’s disease and SSNHL. Candidate immune epitopes were identified that may contribute to pathogenesis of these disorders. While these epitopes await clinical validation, they present novel targets for diagnosis and treatment of sensorineural hearing loss.

New Route for Stem Cell Transplantation into the Cochlea

Objective: Cell transplantation provides a potential method to replace the irreversible loss of auditory hair cells and neurons. In this study, we will prove the intravenous route of stem cell transplantation to the inner ear and the efficacy of the umbilical cord blood-derived mesenchymal stem cell transplantation in hearing restoration of deaf animal model. Method: About 100,000 umbilical cord blood-derived mesenchymal stem cells which were tagged as PKH26 were infused to deaf guinea pigs intravenously. After 1 week and 3 weeks, auditory brainstem response test was checked and we obtained a guinea pig cochlea. A cryosection of each cochlea every 120 μm was obtained and we calculated stem cells for 3 sections of each animal. Results: No hearing gain was shown after stem cell transplantation, but PKH26 tagging mesenchymal stem cell was found in Modiolus, Rosenthal’s canals and organ of Corti. Cells were not found in scala tympani, scala media, and scala vestibuli. Average number of cells in the inner ear was about 88 cells (59-123 cells/section). Most cells were found in spiral ganglion and migrated into the organ of Corti. Conclusion: In this study, we demonstrated that cord blood-derived mesenchymal stem cells could be delivered into the inner ear with intravenous infusion. Based on these results, intravenous injection of stem cells may be used in the treatment of sensorineural hearing loss, regeneration of the auditory hair cells, and neurons.

When Inner Ear Stem Cell Therapy Becomes a Reality

When Inner Ear Stem Cell Therapy Becomes a Reality

Mapping auditory nerve firing density using high-level compound action potentials and high-pass noise masking

Future implementation of regenerative treatments for sensorineural hearing loss may be hindered by the lack of diagnostic tools that specify the target(s) within the cochlea and auditory nerve for delivery of therapeutic agents. Recent research has indicated that the amplitude of high-level compound action potentials (CAPs) is a good predictor of overall auditory nerve survival, but does not pinpoint the location of neural damage. A location-specific estimate of nerve pathology may be possible by using a masking paradigm and high-level CAPs to map auditory nerve firing density throughout the cochlea. This initial study in gerbil utilized a high-pass masking paradigm to determine normative ranges for CAP-derived neural firing density functions using broadband chirp stimuli and low-frequency tonebursts, and to determine if cochlear outer hair cell (OHC) pathology alters the distribution of neural firing in the cochlea. Neural firing distributions for moderate-intensity (60 dB pSPL) chirps were affected by OHC pathology whereas those derived with high-level (90 dB pSPL) chirps were not. These results suggest that CAP-derived neural firing distributions for high-level chirps may provide an estimate of auditory nerve survival that is independent of OHC pathology.

Neural Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells: Applicability for Inner Ear Therapy

Background and ObjectivesRegeneration or replacement of damaged hair cells and neurons in the cochlea might be an ideal treatment for sensorineural hearing loss (SNHL). The purpose of the present study was to investigate whether mesenchymal stem cells (MSCs), derived from the bone marrow of rats, could differentiate into auditory hair cells and neurons.Materials and MethodsThe centrifuge gradient method was used to isolate MSCs from the bone marrow of rats. To confirm whether bone marrow-derived MSCs can differentiate into neuronal cells, culture medium with glial cell-derived neurotrophic factor, brain-derived neurotrophic factor and neurotrophin-3 for 14 days. In addition, immunofluorescence staining and RT-PCR were performed for characterization of the neurospheres and differentiated cells from 7 and 14 day cultures.ResultsThe results showed that MSCs could differentiate into neuron-positive and hair cell-positive cells, using different compositions of growth factors. And RT-PCR result was identified high or low of gene expression all these differentiated cells.ConclusionsRat bone marrow-derived MSCs differentiated into neuronal progenitor cells. These cells might be useful for the treatment of SNHL.

Profound High-Frequency Sensorineural Hearing Loss Treatment With a Totally Implantable Hearing System

This study seeks to assess the efficacy of the Envoy Esteem totally implantable hearing device in treating profound high-frequency sensorineural hearing loss. Five patients with profound high-frequency hearing loss participating in a prospective, multi-center, nonrandomized Food and Drug Administration clinical trial. Implantation with Esteem totally implantable hearing device and comparison to baseline unaided and aided conditions. Speech reception threshold and word recognition scores (WRS) at 50 dB HL presentation level. Preoperative speech reception threshold improved from an unaided 65 dB and aided 48 dB average to 26 dB with the Esteem at 12 months. WRS at 50 dB scores improved from an unaided 10% and aided 23% average to 78% postoperatively. The Esteem totally implantable middle ear hearing device provides appreciable functional gain and improvement in WRS to rehabilitate hearing in patients with a profound high-frequency sensorineural hearing loss.

Regeneration of Hair Cells: Making Sense of All the Noise.

Hearing loss affects hundreds of millions of people worldwide by dampening or cutting off their auditory connection to the world. Current treatments for sensorineural hearing loss (SNHL) with cochlear implants are not perfect, leaving regenerative medicine as the logical avenue to a perfect cure. Multiple routes to regeneration of damaged hair cells have been proposed and are actively pursued. Each route not only requires a keen understanding of the molecular basis of ear development but also faces the practical limitations of stem cell regulation in the delicate inner ear where topology of cell distribution is essential. Improvements in our molecular understanding of the minimal essential genes necessary for hair cell formation and recent advances in stem cell manipulation, such as seen with inducible pluripotent stem cells (iPSCs) and epidermal neural crest stem cells (EPI-NCSCs), have opened new possibilities to advance research in translational stem cell therapies for individuals with hearing loss. Despite this, more detailed network maps of gene expression are needed, including an appreciation for the roles of microRNAs (miRs), key regulators of transcriptional gene networks. To harness the true potential of stem cells for hair cell regeneration, basic science and clinical medicine must work together to expedite the transition from bench to bedside by elucidating the full mechanisms of inner ear hair cell development, including a focus on the role of miRs, and adapting this knowledge safely and efficiently to stem cell technologies.

Biotechnology in the Treatment of Sensorineural Hearing Loss: Foundations and Future of Hair Cell Regeneration

To provide an overview of the methodologies involved in the field of hair cell regeneration. First, the author provides a tutorial on the biotechnological foundations of this field to assist the reader in the comprehension and interpretation of the research involved in hair cell regeneration. Next, the author presents a review of stem cell and gene therapy and provides a critical appraisal of their application to hair cell regeneration. The methodologies used in these approaches are highlighted. The author conducted a narrative review of the fields of cellular, molecular, and developmental biology, tissue engineering, and stem cell and gene therapy using the PubMed database. The use of biotechnological approaches to the treatment of hearing loss--approaches such as stem cell and gene therapy-has led to new methods of regenerating cochlear hair cells in mammals. Incredible strides have been made in assembling important pieces of the puzzle that comprise hair cell regeneration. However, mammalian hair cell regeneration using stem cell and gene therapy are years--if not decades--away from being clinically feasible. If the goals of the biological approaches are met, these therapies may represent future treatments for hearing loss.

Stealth-Nanoparticle Strategy for Enhancing The Efficacy of Steroids in Mice with Noise-Induced Hearing Loss

This study aimed to investigate the efficacy of encapsulating steroids, which is a primary choice for the treatment of sensorineural hearing loss, in polyethylene glycol-coated polylactic acid nanoparticles for drug delivery to the cochlea. We prepared polyethylene glycol-coated polylactic acid nanoparticles encapsulating rhodamine or betamethasone phosphate (BP), and administered them systemically to CBA/N mice previously exposed to intense noise. We assessed nanoparticle distribution using rhodamine fluorescence, BP concentrations in tissues, nuclear translocation of glucocorticoid receptors and the function and histology of the mouse cochleae. Polyethylene glycol-coated polylactic acid nanoparticles delivered BP to cochleae over a sustained period, resulting in significant reductions in histological and functional damage to cochleae and indicating the potential therapeutic benefits of these nanoparticles for enhancing the delivery of BP in acute sensorineural hearing loss.

Strengthen the research on prevention and treatment of sensorineural hearing loss in China

感音神经性聋研究是耳科领域的重中之重。严格意义上，感音神经性聋从病变部位上可划分为感音性和神经性。感音性聋从发生时间可分为先天性和后天获得性两大类。先天性感音性聋又可分为遗传性聋和环境因素致聋（孕期病毒感染等）；后天获得性感音性聋包括突发性聋、噪声性耳聋、老年性耳聋、药物性耳聋等。听神经病属于神经性耳聋范畴。

感音難聴とめまい：病態はどこまで分かったか―蝸牛虚血性障害，音響性障害に対するグルココルチコイド治療―

The effect of glucocorticoids on sensorineural hearing loss of sudden onset remains to be controversial although glucocorticoids have been used for treatment of sudden sensorineural hearing loss. We review recent findings about the effect of glucocorticoids on cochlear ischemic and acoustic injuries obtained from animal experiments. Systemically administered glucocorticoids penetrate the blood-cochlear barrier well. Glucocorticoids ameliorated the cochlear ischemic and acoustic injuries at a relatively wide range of doses, and they protect cochlear hair cells in these types of injury. The therapeutic actions of glucocorticoids in cochlear injuries were considered to be mediated via both genomic and non-genomic pathways. Based on the results obtained in acoustic injury, therapeutic time window of glucocorticoids is considered to be short after the onset of injury. These findings obtained from animal experiments are important in considering clinical usage of glucocorticoids for the treatment of sensorineural hearing loss.

Brain-Derived Nerve Growth Factor in the Treatment of Sensorineural Hearing Loss

Brain-Derived Nerve Growth Factor in the Treatment of Sensorineural Hearing Loss

Potential Novel Drug Carriers for Inner Ear Treatment: Hyperbranched Polylysine and Lipid Nanocapsules

Treatment of sensorineural hearing loss could be advanced using novel drug carriers such as hyperbranched polylysine (HBPL) or lipid nanocapsules (LNCs). This study examined HBPL and LNCs for their cellular uptake and possible toxicity in vitro and in vivo as the first step in developing novel nanosized multifunctional carriers. Having incubated HBPL and LNCs with fibroblasts, nanoparticle uptake and cell viability were determined by confocal laser scanning microscopy, fluorescence measurements and neutral red staining. In vivo, electrophysiology, confocal laser scanning microscopy and cytocochleograms were performed for nanoparticle detection and also toxicity studies after intracochlear application. Both nanoparticles were detectable in the fibroblasts' cytoplasm without causing cytotoxic effects. After in vivo application they were visualized in cochlear cells, which did not lead to a change in hearing threshold or loss of hair cells. Biocompatibility and traceability were demonstrated for HBPL and LNCs. Thus, they comply with the basic requirements for drug carriers for potential application in the inner ear.