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https://www.readbyqxmd.com/read/29351276/static-length-changes-of-cochlear-outer-hair-cells-can-tune-low-frequency-hearing
#1
Nikola Ciganović, Rebecca L Warren, Batu Keçeli, Stefan Jacob, Anders Fridberger, Tobias Reichenbach
The cochlea not only transduces sound-induced vibration into neural spikes, it also amplifies weak sound to boost its detection. Actuators of this active process are sensory outer hair cells in the organ of Corti, whereas the inner hair cells transduce the resulting motion into electric signals that propagate via the auditory nerve to the brain. However, how the outer hair cells modulate the stimulus to the inner hair cells remains unclear. Here, we combine theoretical modeling and experimental measurements near the cochlear apex to study the way in which length changes of the outer hair cells deform the organ of Corti...
January 19, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29342037/preservation-of-cells-of-the-organ-of-corti-and-innervating-dendritic-processes-following-cochlear-implantation-in-the-human-an-immunohistochemical-study
#2
Takefumi Kamakura, Jennifer T O'Malley, Joseph B Nadol
HYPOTHESIS: This study evaluates the degree of preservation of hair cells, supporting cells, and innervating dendritic processes after cochlear implantation in the human using immunohistochemical methods. BACKGROUND: Surgical insertion of a cochlear implant electrode induces various pathologic changes within the cochlea including insertional trauma, foreign body response, inflammation, fibrosis, and neo-osteogenesis. These changes may result in loss of residual acoustic hearing, adversely affecting the use of hybrid implants, and may result in loss of putative precursor cells, limiting the success of future regenerative protocols...
January 16, 2018: Otology & Neurotology
https://www.readbyqxmd.com/read/29336130/comparison-of-three-types-of-mesenchymal-stem-cells-bone-marrow-adipose-tissue-and-umbilical-cord-derived-as-potential-sources-for-inner-ear-regeneration
#3
REVIEW
Mohammad-Reza Mahmoudian-Sani, Ameneh Mehri-Ghahfarrokhi, Morteza Hashemzadeh-Chaleshtori, Masoud Saidijam, Mohammad-Saeid Jami
In this review, we compared the potential of mesenchymal stem cells derived from bone marrow, adipose tissue and umbilical cord as suitable sources for regeneration of inner ear hair cells and auditory neurons. Our intensive literature search indicates that stem cells in some of adult mammalian tissues, such as bone marrow, can generate new cells under physiological and pathological conditions. Among various types of stem cells, bone marrow-derived mesenchymal stem cells are one of the most promising candidates for cell replacement therapy...
December 1, 2017: International Tinnitus Journal
https://www.readbyqxmd.com/read/29323051/notch-pathway-inhibitor-dapt-enhances-atoh1-activity-to-generate-new-hair-cells-in-situ-in-rat-cochleae
#4
Wen-Wei Luo, Zhao Han, Dong-Dong Ren, Xin-Wei Wang, Fang-Lu Chi, Juan-Mei Yang
Atoh1 overexpression in cochlear epithelium induces new hair cell formation. Use of adenovirus-mediated Atoh1 overexpression has mainly focused on the rat lesser epithelial ridge and induces ectopic hair cell regeneration. The sensory region of rat cochlea is difficult to transfect, thus new hair cells are rarely produced in situ in rat cochlear explants. After culturing rat cochleae in medium containing 10% fetal bovine serum, adenovirus successfully infected the sensory region as the width of the supporting cell area was significantly increased...
December 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29321651/auditory-neural-activity-in-congenitally-deaf-mice-induced-by-infrared-neural-stimulation
#5
Xiaodong Tan, Israt Jahan, Yingyue Xu, Stuart Stock, Changyow Claire Kwan, Carmen Soriano, Xianghui Xiao, Jaime García-Añoveros, Bernd Fritzsch, Claus-Peter Richter
To determine whether responses during infrared neural stimulation (INS) result from the direct interaction with spiral ganglion neurons (SGNs), we tested three genetically modified deaf mouse models: Atoh1-cre; Atoh1 f/f (Atoh1 conditional knockout, CKO), Atoh1-cre; Atoh1 f/kiNeurog1 (Neurog1 knockin, KI), and the Vglut3 knockout (Vglut3 -/-) mice. All animals were exposed to tone bursts and clicks up to 107 dB (re 20 µPa) and to INS, delivered with a 200 µm optical fiber. The wavelength (λ) was 1860 nm, the radiant energy (Q) 0-800 µJ/pulse, and the pulse width (PW) 100-500 µs...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29258297/treatment-of-autosomal-dominant-hearing-loss-by-in-vivo-delivery-of-genome-editing-agents
#6
Xue Gao, Yong Tao, Veronica Lamas, Mingqian Huang, Wei-Hsi Yeh, Bifeng Pan, Yu-Juan Hu, Johnny H Hu, David B Thompson, Yilai Shu, Yamin Li, Hongyang Wang, Shiming Yang, Qiaobing Xu, Daniel B Polley, M Charles Liberman, Wei-Jia Kong, Jeffrey R Holt, Zheng-Yi Chen, David R Liu
Although genetic factors contribute to almost half of all cases of deafness, treatment options for genetic deafness are limited. We developed a genome-editing approach to target a dominantly inherited form of genetic deafness. Here we show that cationic lipid-mediated in vivo delivery of Cas9-guide RNA complexes can ameliorate hearing loss in a mouse model of human genetic deafness. We designed and validated, both in vitro and in primary fibroblasts, genome editing agents that preferentially disrupt the dominant deafness-associated allele in the Tmc1 (transmembrane channel-like gene family 1) Beethoven (Bth) mouse model, even though the mutant Tmc1Bth allele differs from the wild-type allele at only a single base pair...
December 20, 2017: Nature
https://www.readbyqxmd.com/read/29240567/theoretical-evaluation-and-experimental-validation-of-localized-therapeutic-hypothermia-application-to-preserve-residual-hearing-after-cochlear-implantation
#7
Ilmar Tamames, Curtis King, Chin-Yuh Huang, Fred F Telischi, Michael E Hoffer, Suhrud M Rajguru
OBJECTIVES: Cochlear implantation surgery has been shown to result in trauma to inner ear sensory structures, resulting in loss of residual hearing. Localized therapeutic hypothermia has been shown in clinical care to be a neuroprotective intervention. Previously, we have shown in an experimental model that localized hypothermia protects cochlear hair cells and residual hearing function against surgical and cochlear implantation trauma. Using experimental temperature measurements carried out in human cadaver temporal bones and a finite element model of the inner ear, the present study examined the temperature distribution of a custom-designed hypothermia delivery system in the human inner ear organs...
December 13, 2017: Ear and Hearing
https://www.readbyqxmd.com/read/29234270/mouse-panx1-is-dispensable-for-hearing-acquisition-and-auditory-function
#8
Veronica Zorzi, Fabiola Paciello, Gaia Ziraldo, Chiara Peres, Flavia Mazzarda, Chiara Nardin, Miriam Pasquini, Francesco Chiani, Marcello Raspa, Ferdinando Scavizzi, Andrea Carrer, Giulia Crispino, Catalin D Ciubotaru, Hannah Monyer, Anna R Fetoni, Anna M Salvatore, Fabio Mammano
Panx1 forms plasma membrane channels in brain and several other organs, including the inner ear. Biophysical properties, activation mechanisms and modulators of Panx1 channels have been characterized in detail, however the impact of Panx1 on auditory function is unclear due to conflicts in published results. To address this issue, hearing performance and cochlear function of the Panx1-/- mouse strain, the first with a reported global ablation of Panx1, were scrutinized. Male and female homozygous (Panx1-/-), hemizygous (Panx1+/-) and their wild type (WT) siblings (Panx1+/+) were used for this study...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29223865/prevention-of-ischemia-induced-hearing-loss-by-intravenous-administration-of-hydrogen-rich-saline-in-gerbil
#9
Hideo Ogawa, Masahiro Okada, Masachika Shudou, Kiyofumi Gyo, Naohito Hatoa
OBJECTIVE: Hydrogen-rich water, which is a potent antioxidant agent, was investigated for its protective effects against ischemic damage of the cochlea in gerbils. METHODS: The animals were subjected to transient cochlear ischemia by occluding the bilateral vertebral arteries for l5minutes. Five milliliters of hydrogen-rich saline was then intravenously administered immediately after the insult. Saline without hydrogen was used as a control. Effects of hydrogen were evaluated using the auditory brainstem response (ABR) and histological studies of the inner ear...
December 6, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29207085/chronic-prenatal-hypoxia-impairs-cochlear-development-a-mechanism-involving-connexin26-expression-and-promoter-methylation
#10
Jingcang Lin, Huang Huang, Guorong Lv, Xiangyang Xu, Wendong Lin, Xianyan Xu, Jing Cheng, Ming Zheng
Chronic prenatal hypoxia is a damaging to fetal development and may have various consequences, including hearing loss. Connexin 26 (Cx26) is one of the major protein subunits required for gap junction formation, and has an important role in maintaining homeostasis in the cochlea and normal hearing. Cx26 mutation and expression abnormality are closely associated with inherited nonsyndromic deafness, but the association between Cx26 and prenatal hypoxia is less established. The present study aimed to examine Cx26 expression and aberrant methylation the Cx26 promoter region in the cochlea from rats exposed to chronic prenatal hypoxia...
December 1, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29194212/evaluation-of-mitoquinone-for-protecting-against-amikacin-induced-ototoxicity-in-guinea-pigs
#11
Carolyn O Dirain, Maria Raye Ann V Ng, Bailey Milne-Davies, Jerin K Joseph, Patrick J Antonelli
HYPOTHESIS: Mitoquinone (MitoQ) attenuates amikacin ototoxicity in guinea pigs. BACKGROUND: MitoQ, a mitochondria-targeted derivative of the antioxidant ubiquinone, has improved bioavailability and demonstrated safety in humans. Thus, MitoQ is a promising therapeutic approach for protecting against amikacin-induced ototoxicity. METHODS: Both oral and subcutaneous administrations of MitoQ were tested. Amikacin-treated guinea pigs (n = 12-18 per group) received water alone (control) or MitoQ 30 mg/l-supplemented drinking water; or injected subcutaneously with 3 to 5 mg/kg MitoQ or saline (control)...
November 29, 2017: Otology & Neurotology
https://www.readbyqxmd.com/read/29182629/effects-of-peroxisome-proliferator-activated-receptors-ppar-%C3%AE-and-%C3%AE-agonists-on-cochlear-protection-from-oxidative-stress
#12
Marijana Sekulic-Jablanovic, Vesna Petkovic, Matthew B Wright, Krystsina Kucharava, Nathan Huerzeler, Soledad Levano, Yves Brand, Katharina Leitmeyer, Andrea Glutz, Alexander Bausch, Daniel Bodmer
Various insults cause ototoxicity in mammals by increasing oxidative stress leading to apoptosis of auditory hair cells (HCs). The thiazolidinediones (TZDs; e.g., pioglitazone) and fibrate (e.g., fenofibrate) drugs are used for the treatment of diabetes and dyslipidemia. These agents target the peroxisome proliferator-activated receptors, PPARγ and PPARα, which are transcription factors that influence glucose and lipid metabolism, inflammation, and organ protection. In this study, we explored the effects of pioglitazone and other PPAR agonists to prevent gentamicin-induced oxidative stress and apoptosis in mouse organ of Corti (OC) explants...
2017: PloS One
https://www.readbyqxmd.com/read/29181442/weak-middle-ear-muscle-reflex-in-humans-with-noise-induced-tinnitus-and-normal-hearing-may-reflect-cochlear-synaptopathy
#13
Magdalena Wojtczak, Jordan A Beim, Andrew J Oxenham
Chronic tinnitus is a prevalent hearing disorder, and yet no successful treatments or objective diagnostic tests are currently available. The aim of this study was to investigate the relationship between the presence of tinnitus and the strength of the middle-ear-muscle reflex (MEMR) in humans with normal and near-normal hearing. Clicks were used as test stimuli to obtain a wideband measure of the effect of reflex activation on ear-canal sound pressure. The reflex was elicited using a contralateral broadband noise...
November 2017: ENeuro
https://www.readbyqxmd.com/read/29163050/mechanisms-of-cisplatin-induced-ototoxicity-and-otoprotection
#14
REVIEW
Sandeep Sheth, Debashree Mukherjea, Leonard P Rybak, Vickram Ramkumar
Evidence of significant hearing loss during the early days of use of cisplatin as a chemotherapeutic agent in cancer patients has stimulated research into the causes and treatment of this side effect. It has generally been accepted that hearing loss is produced by excessive generation of reactive oxygen species (ROS) in cell of the cochlea, which led to the development of various antioxidants as otoprotective agents. Later studies show that ROS could stimulate cochlear inflammation, suggesting the use of anti-inflammatory agents for treatment of hearing loss...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29152945/dna-methylation-of-the-prestin-gene-and-outer-hair-cell-electromotileresponse-of-the-cochlea-in-salicylate-administration
#15
(no author information available yet)
Background/aim: Activity of the prestin gene may have a role in the pathogenesis of salicylate-induced ototoxicity. We investigated DNA methylation for prestin gene exon 1 in salicylate-injected guinea pigs.Materials and methods: Fifteen guinea pigs (30 ears) underwent audiological evaluation including 1000 Hz probe-tone tympanometry and a distortion product otoacoustic emission (DPOAE) test. The animals were randomly divided into three groups. Groups 2 (8 ears) and 3 (14 ears) were injected with intramuscular saline and sodium salicylate (200 mg/kg), respectively twice daily for 2 weeks...
November 13, 2017: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/29130354/delivery-of-adeno-associated-viral-vectors-in-adult-mammalian-inner-ear-cell-subtypes-without-auditory-dysfunction
#16
Yong Tao, Mingqian Huang, Yilai Shu, Adam Ruprecht, Hongyang Wang, Yong Tang, Luk H Vandenberghe, Qiuju Wang, Guangping Gao, Wei-Jia Kong, Zheng-Yi Chen
Hearing loss, including genetic hearing loss, is one of the most common forms of sensory deficits in human with limited options of treatment. Adeno-associated virus (AAV)-mediated gene transfer has been shown to effectively recover auditory functions in mouse models of genetic deafness when delivered at neonatal stages. However, the mouse cochlea is still developing at those time points whereas in human the newborn inner ears are already fully mature. For effective gene therapy to treat genetic deafness, it is necessary to determine whether or not AAV-mediated therapy can be equally effective in the fully mature mouse inner ear without causing damages to the inner ear...
November 12, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29107847/the-fbn-rat-model-of-aging-investigation-of-abr-waveforms-and-ribbon-synapse-changes
#17
Rui Cai, Scott C Montgomery, Kaley A Graves, Donald M Caspary, Brandon C Cox
Age-related hearing loss is experienced by one-third of individuals aged 65 years and older and can be socially debilitating. Historically, there has been poor correlation between age-related threshold changes, loss of speech understanding, and loss of cochlear hair cells. We examined changes in ribbon synapse number at four different ages in Fisher Brown Norway rats, an extensively studied rat model of aging. In contrast to previous work in mice/Wistar rats, we found minimal ribbon synapse loss before 20 months, with significant differences in 24- and 28-month-old rats at 4 kHz...
October 9, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29107558/esrp1-mutations-cause-hearing-loss-due-to-defects-in-alternative-splicing-that-disrupt-cochlear-development
#18
Alex M Rohacek, Thomas W Bebee, Richard K Tilton, Caleb M Radens, Chris McDermott-Roe, Natoya Peart, Maninder Kaur, Michael Zaykaner, Benjamin Cieply, Kiran Musunuru, Yoseph Barash, John A Germiller, Ian D Krantz, Russ P Carstens, Douglas J Epstein
Alternative splicing contributes to gene expression dynamics in many tissues, yet its role in auditory development remains unclear. We performed whole-exome sequencing in individuals with sensorineural hearing loss (SNHL) and identified pathogenic mutations in Epithelial Splicing-Regulatory Protein 1 (ESRP1). Patient-derived induced pluripotent stem cells showed alternative splicing defects that were restored upon repair of an ESRP1 mutant allele. To determine how ESRP1 mutations cause hearing loss, we evaluated Esrp1(-/-) mouse embryos and uncovered alterations in cochlear morphogenesis, auditory hair cell differentiation, and cell fate specification...
November 6, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29093662/tmc2-modifies-permeation-properties-of-the-mechanoelectrical-transducer-channel-in-early-postnatal-mouse-cochlear-outer-hair-cells
#19
Laura F Corns, Jing-Yi Jeng, Guy P Richardson, Corné J Kros, Walter Marcotti
The ability of cochlear hair cells to convert sound into receptor potentials relies on the mechanoelectrical transducer (MET) channels present in their stereociliary bundles. There is strong evidence implying that transmembrane channel-like protein (TMC) 1 contributes to the pore-forming subunit of the mature MET channel, yet its expression is delayed (~>P5 in apical outer hair cells, OHCs) compared to the onset of mechanotransduction (~P1). Instead, the temporal expression of TMC2 coincides with this onset, indicating that it could be part of the immature MET channel...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29092611/modeling-signal-propagation-in-the-human-cochlea
#20
Stephen T Neely, Daniel M Rasetshwane
The level-dependent component of the latency of human auditory brainstem responses (ABR) to tonebursts decreases by about 38% for every 20-dB increase in stimulus level over a wide range of both frequency and level [Neely, Norton, Gorga, and Jesteadt (1998). J. Acoust. Soc. Am. 31, 87-97]. This level-dependence has now been simulated in an active, nonlinear, transmission-line model of cochlear mechanics combined with an adaptation stage. The micromechanics in this model are similar to previous models except that a dual role is proposed for the tectorial membrane (TM): (1) passive sharpening the tuning of sensory-cell inputs (relative to basilar-membrane vibrations) and (2) providing an optimal phase shift (relative to basilar-membrane vibrations) of outer-hair-cell feedback forces, so that amplification is restricted to a limited range of frequencies...
October 2017: Journal of the Acoustical Society of America
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