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https://www.readbyqxmd.com/read/28806331/cochlear-implants-meet-regenerative-biology-state-of-the-science-and-future-research-directions
#1
Alain Dabdoub, Koji Nishimura
: The cochlear implant, the first device to restore a human sense, is an electronic substitute for lost mechanosensory hair cells. It has been successful at providing hearing to people with severe to profound hearing loss and as of 2012, an estimated 324,000 patients worldwide have received cochlear implants. Users of cochlear implants however, suffer from difficulties in processing complex sounds such as music and in discriminating sounds in noisy environments. Recent advances in regenerative biology and medicine are opening new avenues for enhancing the efficacy of cochlear implants by improving the neural interface in the future and offer the possibility of an entirely biological solution for hearing loss in the long term...
September 2017: Otology & Neurotology
https://www.readbyqxmd.com/read/28806329/physiological-mechanisms-in-combined-electric-acoustic-stimulation
#2
Mika Sato, Peter Baumhoff, Jochen Tillein, Andrej Kral
OBJECTIVE: Electrical stimulation is normally performed on ears that have no hearing function, i.e., lack functional hair cells. The properties of electrically-evoked responses in these cochleae were investigated in several previous studies. Recent clinical developments have introduced cochlear implantation (CI) in residually-hearing ears to improve speech understanding in noise. The present study documents the known physiological differences between electrical stimulation of hair cells and of spiral ganglion cells, respectively, and reviews the mechanisms of combined electric and acoustic stimulation in the hearing ears...
September 2017: Otology & Neurotology
https://www.readbyqxmd.com/read/28796092/oral-administration-of-clinical-stage-drug-candidate-sens-401-effectively-reduces-cisplatin-induced-hearing-loss-in-rats
#3
Mathieu Petremann, Christophe Tran Van Ba, Audrey Broussy, Charlotte Romanet, Jonas Dyhrfjeld-Johnsen
HYPOTHESIS: SENS-401, an oral clinical-stage drug, may reduce cisplatin-induced hearing loss and cochlear damage in an in vivo model. BACKGROUND: Cisplatin is commonly associated with hearing loss, causing significant learning and behavioral difficulties in the pediatric cancer population, and for which there are currently no clinical solutions. SENS-401 has previously been shown to improve acoustic trauma-induced hearing loss in vivo. METHODS: The effect of SENS-401 (R-azasetron besylate) on cisplatin IC50 values was evaluated in a panel of cisplatin-sensitive cell lines (NIH:OVCAR-3, SK-N-AS, NCI-H460, FaDu)...
August 8, 2017: Otology & Neurotology
https://www.readbyqxmd.com/read/28776202/neurotrophin-gene-therapy-in-deafened-ears-with-cochlear-implants-long-term-effects-on-nerve-survival-and-functional-measures
#4
Bryan E Pfingst, Deborah J Colesa, Donald L Swiderski, Aaron P Hughes, Stefan B Strahl, Moaz Sinan, Yehoash Raphael
Because cochlear implants function by stimulating the auditory nerve, it is assumed that the condition of the nerve plays an important role in the efficacy of the prosthesis. Thus, considerable research has been devoted to methods of preserving the nerve following deafness. Neurotrophins have been identified as a potential contributor to neural health, but most of the research to date has been done in young animals and for short periods (less than 3 to 6 months) after the onset of treatment. The first objective of the current experiment was to examine the effects of a neurotrophin gene therapy delivery method on spiral ganglion neuron (SGN) preservation and function in the long term (5 to 14 months) in mature guinea pigs with cochlear implants...
August 3, 2017: Journal of the Association for Research in Otolaryngology: JARO
https://www.readbyqxmd.com/read/28769753/intraoperative-electrocochleographic-characteristics-of-auditory-neuropathy-spectrum-disorder-in-cochlear-implant-subjects
#5
William J Riggs, Joseph P Roche, Christopher K Giardina, Michael S Harris, Zachary J Bastian, Tatyana E Fontenot, Craig A Buchman, Kevin D Brown, Oliver F Adunka, Douglas C Fitzpatrick
Auditory neuropathy spectrum disorder (ANSD) is characterized by an apparent discrepancy between measures of cochlear and neural function based on auditory brainstem response (ABR) testing. Clinical indicators of ANSD are a present cochlear microphonic (CM) with small or absent wave V. Many identified ANSD patients have speech impairment severe enough that cochlear implantation (CI) is indicated. To better understand the cochleae identified with ANSD that lead to a CI, we performed intraoperative round window electrocochleography (ECochG) to tone bursts in children (n = 167) and adults (n = 163)...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28766844/timing-of-cochlear-implantation-in-auditory-neuropathy-patients-with-otof-mutations-our-experience-with-10-patients
#6
C C Wu, C J Hsu, F L Huang, Y H Lin, Y H Lin, T C Liu, C M Wu
Auditory neuropathy spectrum disorder (ANSD) can be caused by a variety of pathologies ranging from inner hair cells, synapses, spiral ganglion neurons, the auditory nerve, to brainstem auditory nuclei.(1) For ANSD patients who derive limited benefit from hearing aids, cochlear implantation constitutes the treatment of last resort. However, corresponding to the heterogeneity in pathology, the outcomes with cochlear implants (CIs) vary significantly among ANSD patients.(1) This article is protected by copyright...
August 2, 2017: Clinical Otolaryngology
https://www.readbyqxmd.com/read/28756190/mir-34a-bcl-2-signaling-pathway-contributes-to-age-related-hearing-loss-by-modulating-hair-cell-apoptosis
#7
Qiuhong Huang, Yiqing Zheng, Yongkang Ou, Hao Xiong, Haidi Yang, Zhigang Zhang, Suijun Chen, Yongyi Ye
MicroRNAs, such as miR-34, have been reported to influence age-related diseases. In this study, we explored the role of the miR-34a/Bcl-2 signaling pathway in age-related hearing loss (AHL). Using an AHL mouse model (C57BL/6), we found that the expression of miR-34a in the cochlea increased with age, whereas expression of Bcl-2 decreased. Increasing the amount of a miR-34a mimetic in a mouse auditory cell line (HEI-OC1) inhibited Bcl-2, leading to enhanced apoptosis; in contrast, miR-34a inhibition produced the opposite effect...
July 26, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28747011/bioconversion-of-scutellaria-baicalensis-extract-can-increase-recovery-of-auditory-function-in-a-mouse-model-of-noise-induced-hearing-loss
#8
Isabel Rodriguez, Bin Na Hong, Youn Hee Nam, Eun Young Kim, Geun Ha Park, Min Gun Ji, Tong Ho Kang
In noise-induced hearing loss (NIHL), noise exposure damages cochlear sensory hair cells, which lack the capacity to regenerate. Following noise insult, intense metabolic activity occurs, resulting in a cochlear free radical imbalance. Oxidative stress and antioxidant enzyme alterations, including lipoxygenase upregulation, have been linked to chronic inflammation, which contributes to hearing impairment. We previously proposed Scutellaria baicalensis (SB) extract as an alternative therapeutic for preventing NIHL and attributed its pharmacological effects to baicalein...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28743950/auditory-neuropathy-after-damage-to-cochlear-spiral-ganglion-neurons-in-mice-resulting-from-conditional-expression-of-diphtheria-toxin-receptors
#9
Haolai Pan, Qiang Song, Yanyan Huang, Jiping Wang, Renjie Chai, Shankai Yin, Jian Wang
Auditory neuropathy (AN) is a hearing disorder characterized by normal cochlear amplification to sound but poor temporal processing and auditory perception in noisy backgrounds. These deficits likely result from impairments in auditory neural synchrony; such dyssynchrony of the neural responses has been linked to demyelination of auditory nerve fibers. However, no appropriate animal models are currently available that mimic this pathology. In this study, Cre-inducible diphtheria toxin receptor (iDTR (+/+) ) mice were cross-mated with mice containing Cre (Bhlhb5-Cre (+/-) ) specific to spiral ganglion neurons (SGNs)...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28735085/minocycline-attenuates-streptomycin-induced-cochlear-hair-cell-death-by-inhibiting-protein-nitration-and-poly-adp-ribose-polymerase-activation
#10
Ping Wang, Haonan Li, Shuyuan Yu, Peng Jin, Abdurahman Hassan, Bo Du
This study aimed to elucidate the protective effect of minocycline against streptomycin-induced damage of cochlear hair cells and its mechanism. Cochlear membranes were isolated from newborn Wistar rats and randomly divided into control, 500μmol/L streptomycin, 100μmol/L minocycline, and streptomycin and minocycline treatment groups. Hair cell survival was analyzed by detecting the expression of 3-nitrotyrosine (3-NT) in cochlear hair cells by immunofluorescence and an enzyme-linked immunosorbent assay. Expression of 3-NT and inducible nitric oxide synthase (iNOS), and poly (ADP-Ribose) polymerase (PARP) and caspase-3 activation were evaluated by western blotting...
July 19, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28729444/an-atoh1-s193a-phospho-mutant-allele-causes-hearing-deficits-and-motor-impairment
#11
Wei Rose Xie, Hsin-I Jen, Michelle L Seymour, Szu-Ying Yeh, Fred A Pereira, Andrew K Groves, Tiemo J Klisch, Huda Y Zoghbi
Atoh1 is a basic helix-loop-helix (bHLH) transcription factor that is essential for the genesis, survival, and maturation of a variety of neuronal and non-neuronal cell populations, including those involved in proprioception, interoception, balance, respiration, and hearing. Such diverse functions require fine regulation at the transcriptional and protein levels. Here we show that serine 193 (S193) is phosphorylated in Atoh1's bHLH domain in vivo Knock-in mice of both sexes bearing a GFP-tagged phospho-dead S193A allele on a null background (Atoh1(S193A/lacZ) ) exhibit mild cerebellar foliation defects, motor impairments, and also partial pontine nucleus migration defects, cochlear hair cell degeneration, and profound hearing loss...
July 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28717876/structural-and-ultrastructural-changes-to-type-i-spiral-ganglion-neurons-and-schwann-cells-in-the-deafened-guinea-pig-cochlea
#12
Andrew K Wise, Remy Pujol, Thomas G Landry, James B Fallon, Robert K Shepherd
Sensorineural hearing loss is commonly caused by damage to cochlear sensory hair cells. Coinciding with hair cell degeneration, the peripheral fibres of type I spiral ganglion neurons (SGNs) that normally form synaptic connections with the inner hair cell gradually degenerate. We examined the time course of these degenerative changes in type I SGNs and their satellite Schwann cells at the ultrastructural level in guinea pigs at 2, 6, and 12 weeks following aminoglycoside-induced hearing loss. Degeneration of the peripheral fibres occurred prior to the degeneration of the type I SGN soma and was characterised by shrinkage of the fibre followed by retraction of the axoplasm, often leaving a normal myelin lumen devoid of axoplasmic content...
July 17, 2017: Journal of the Association for Research in Otolaryngology: JARO
https://www.readbyqxmd.com/read/28713423/discovering-the-unexpected-with-the-utilization-of-ngs-in-diagnostics-of-non-syndromic-hearing-loss-disorders-the-family-case-of-ildr1-dependent-hearing-loss-disorder
#13
Jernej Kovač, Gašper Klančar, Katarina Trebušak Podkrajšek, Saba Battelino
Sensorineural hearing loss (SNHL) is a heterogeneous family of hearing disabilities with congenital (including genetic) as well as acquired etiology. Congenital SNHL of genetic etiology is further sub-divided into autosomal dominant, autosomal recessive and X-linked SNHL. More than 60 genes are involved in the etiology of autosomal recessive non-syndromic hearing loss (ARNSHL) commonly manifesting as heterogeneous pre-lingual profound to severe non-progressive clinical phenotype. ILDR1-dependent ARNSHL (DFNB42, OMIM: # 609646) is a very rare sub-type of hearing disability, with unknown prevalence, caused by function-damaging genetic variants in ILDR1 gene reported in families of Middle-Eastern origin...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28712672/noise-induced-cochlear-synaptopathy-in-rhesus-monkeys-macaca-mulatta
#14
M D Valero, J A Burton, S N Hauser, T A Hackett, R Ramachandran, M C Liberman
Cochlear synaptopathy can result from various insults, including acoustic trauma, aging, ototoxicity, or chronic conductive hearing loss. For example, moderate noise exposure in mice can destroy up to ∼50% of synapses between auditory nerve fibers (ANFs) and inner hair cells (IHCs) without affecting outer hair cells (OHCs) or thresholds, because the synaptopathy occurs first in high-threshold ANFs. However, the fiber loss likely impairs temporal processing and hearing-in-noise, a classic complaint of those with sensorineural hearing loss...
July 8, 2017: Hearing Research
https://www.readbyqxmd.com/read/28705869/auditory-cortex-interneuron-development-requires-cadherins-operating-hair-cell-mechanoelectrical-transduction
#15
Baptiste Libé-Philippot, Vincent Michel, Jacques Boutet de Monvel, Sébastien Le Gal, Typhaine Dupont, Paul Avan, Christine Métin, Nicolas Michalski, Christine Petit
Many genetic forms of congenital deafness affect the sound reception antenna of cochlear sensory cells, the hair bundle. The resulting sensory deprivation jeopardizes auditory cortex (AC) maturation. Early prosthetic intervention should revive this process. Nevertheless, this view assumes that no intrinsic AC deficits coexist with the cochlear ones, a possibility as yet unexplored. We show here that many GABAergic interneurons, from their generation in the medial ganglionic eminence up to their settlement in the AC, express two cadherin-related (cdhr) proteins, cdhr23 and cdhr15, that form the hair bundle tip links gating the mechanoelectrical transduction channels...
July 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28703809/epigallocatechin-3-gallate-a-prototypic-chemopreventative-agent-for-protection-against-cisplatin-based-ototoxicity
#16
Vikrant Borse, Raheem F H Al Aameri, Kelly Sheehan, Sandeep Sheth, Tejbeer Kaur, Debashree Mukherjea, Srinivasan Tupal, Michelle Lowy, Sumana Ghosh, Asmita Dhukhwa, Puspanjali Bhatta, Leonard P Rybak, Vickram Ramkumar
Cisplatin-induced ototoxicity is one of the major factors limiting cisplatin chemotherapy. Ototoxicity results from damage to outer hair cells (OHCs) and other regions of the cochlea. At the cellular level, cisplatin increases reactive oxygen species (ROS) leading to cochlear inflammation and apoptosis. Thus, ideal otoprotective drugs should target oxidative stress and inflammatory mechanisms without interfering with cisplatin's chemotherapeutic efficacy. In this study, we show that epigallocatechin-3-gallate (EGCG) is a prototypic agent exhibiting these properties of an effect otoprotective agent...
July 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28701711/amplification-mode-differs-along-the-length-of-the-mouse-cochlea-as-revealed-by-connexin-26-deletion-from-specific-gap-junctions
#17
Victoria A Lukashkina, Tetsuji Yamashita, Jian Zuo, Andrei N Lukashkin, Ian J Russell
The sharp frequency tuning and exquisite sensitivity of the mammalian cochlea is due to active forces delivered by outer hair cells (OHCs) to the cochlear partition. Force transmission is mediated and modulated by specialized cells, including Deiters' cells (DCs) and pillar cells (PCs), coupled by gap-junctions composed of connexin 26 (Cx26) and Cx30. We created a mouse with conditional Cx26 knock-out (Cx26 cKO) in DCs and PCs that did not influence sensory transduction, receptor-current-driving-voltage, low-mid-frequency distortion-product-otoacoustic-emissions (DPOAEs), and passive basilar membrane (BM) responses...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28690836/noise-induced-and-age-related-hearing-loss-%C3%A2-new-perspectives-and-potential-therapies
#18
REVIEW
M Charles Liberman
The classic view of sensorineural hearing loss has been that the primary damage targets are hair cells and that auditory nerve loss is typically secondary to hair cell degeneration. Recent work has challenged that view. In noise-induced hearing loss, exposures causing only reversible threshold shifts (and no hair cell loss) nevertheless cause permanent loss of >50% of the synaptic connections between hair cells and the auditory nerve. Similarly, in age-related hearing loss, degeneration of cochlear synapses precedes both hair cell loss and threshold elevation...
2017: F1000Research
https://www.readbyqxmd.com/read/28689068/efficient-induction-of-inner-ear-hair-cell-like-cells-from-mouse-es-cells-using-combination-of-math1-transfection-and-conditioned-medium-from-st2-stromal-cells
#19
Yukiteru Ouji, Masaharu Sakagami, Hiroko Omori, Shinji Higashiyama, Norikazu Kawai, Tadashi Kitahara, Akio Wanaka, Masahide Yoshikawa
We sought to establish a more efficient technique for induction of inner ear hair cell-like cells (HC-like cells) from embryonic stem cells (ES cells) by using a combination of two previously reported methods; ST2 stromal cell-conditioned medium, known to be favorable for HC-like cell induction (HIST2 method), and ES cells with transfer of the Math1 gene (Math1-ES cells). Math1-ES cells carrying Tet-inducible Math1 were cultured for 14days with doxycycline in conditioned medium from cultures of ST2 stromal cells following formation of 4-day embryoid bodies (EBs)...
July 1, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28688549/curcumin-protects-against-acoustic-trauma-in-the-rat-cochlea
#20
Harun Soyalıç, Fikret Gevrek, Serhat Karaman
OBJECTIVES: In this study we evaluated the therapeutic utility of curcumin in a rodent model of acoustic trauma using histopathology, immunohistochemical, and distortion product otoacoustic emission (DPOAEs) measurements. METHODS: 28 Wistar albino rats were included in the study and randomly assigned to 4 treatment groups. The first group (group 1) served as the control and was exposed to acoustic trauma alone. Group 2 was the curcumin group. Group 3 was the curcumin plus acoustic trauma group...
August 2017: International Journal of Pediatric Otorhinolaryngology
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