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https://www.readbyqxmd.com/read/28646272/rhesus-cochlear-and-vestibular-functions-are-preserved-after-inner-ear-injection-of-saline-volume-sufficient-for-gene-therapy-delivery
#1
Chenkai Dai, Mohamed Lehar, Daniel Q Sun, Lani Swarthout Rvt, John P Carey, Tim MacLachlan, Doug Brough, Hinrich Staecker, Alexandra M Della Santina, Timothy E Hullar, Charles C Della Santina
Sensorineural losses of hearing and vestibular sensation due to hair cell dysfunction are among the most common disabilities. Recent preclinical research demonstrates that treatment of the inner ear with a variety of compounds, including gene therapy agents, may elicit regeneration and/or repair of hair cells in animals exposed to ototoxic medications or other insults to the inner ear. Delivery of gene therapy may also offer a means for treatment of hereditary hearing loss. However, injection of a fluid volume sufficient to deliver an adequate dose of a pharmacologic agent could, in theory, cause inner ear trauma that compromises functional outcome...
June 23, 2017: Journal of the Association for Research in Otolaryngology: JARO
https://www.readbyqxmd.com/read/28642685/rab-interacting-molecules-2-and-3-directly-interact-with-the-pore-forming-cav1-3-ca-2-channel-subunit-and-promote-its-membrane-expression
#2
Maria M Picher, Ana-Maria Oprişoreanu, SangYong Jung, Katrin Michel, Susanne Schoch, Tobias Moser
Rab interacting molecules (RIMs) are multi-domain proteins that positively regulate the number of Ca(2+) channels at the presynaptic active zone (AZ). Several molecular mechanisms have been demonstrated for RIM-binding to components of the presynaptic Ca(2+) channel complex, the key signaling element at the AZ. Here, we report an interaction of the C2B domain of RIM2α and RIM3γ with the C-terminus of the pore-forming α-subunit of CaV1.3 channels (CaV1.3α1), which mediate stimulus-secretion coupling at the ribbon synapses of cochlear inner hair cells (IHCs)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28636736/the-protective-effect-of-intratympanic-dexamethasone-on-streptomycin-ototoxicity-in-rats
#3
Aylin Gül, Engin Şengül, Beyhan Yılmaz, Fazıl Emre Özkurt, Mehmet Akdağ, Ayşenur Keleş, İsmail Topçu
The purpose of this experimental study was to investigate the protective role of intratympanically administered dexamethasone on the inner ears of rats that were exposed to streptomycin ototoxicity. Twenty-four adult Wistar albino rats were separated into 4 groups: Group 1 (only streptomycin), Group 2 (only intratympanic dexamethasone), Group 3 (streptomycin and intratympanic dexamethasone), and Group 4 (streptomycin and intratympanic saline). All rats were evaluated with distortion product otoacoustic emissions (DPOAE) tests before the start of treatment and on the day it ended...
June 2017: Ear, Nose, & Throat Journal
https://www.readbyqxmd.com/read/28628154/-morphological-changes-on-cochlear-hair-cells-of-rats-in-simulated-weightlessness-and-inboard-noise
#4
(no author information available yet)
OBJECTIVE: To observe the morphological changes on cochlear hair cells of rats in simulated weightlessness and inboard noise and to investigate the different changes in three turns of hair cells. METHODS: Thirty-two healthy SD rats, all males, were randomly divided into four groups: control group, weightlessness group, noise group and weightlessness+noise groups (n=8). Then rats were exposed to -30° head down tilt as simulated weightlessness and inboard noise including steady-state noise which was (72±2) dB SPL and impulse noise up to 160 dB SPL in spaceship environment...
June 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/28627458/sirna-loaded-biodegradable-nanocarriers-for-therapeutic-mapk1-silencing-against-cisplatin-induced-ototoxicity
#5
Ibrahima Youm, Matthew B West, Wei Li, Xiaoping Du, Donald L Ewert, Richard D Kopke
Ototoxicity represents a major adverse side-effect of cis-diamminedichloroplatinum-II (cisplatin, CDDP). The mitogen-activated protein kinase (MAPK) pathway is thought to play a central role in potentiating the apoptotic effect of CDDP within the cochlea. We hypothesized that prophylactic inhibition of MAPK signaling, using small interfering RNA (siRNA), might confer a protective effect against CDDP-induced apoptosis within the auditory sensory epithelia. To enhance the therapeutic utility of this approach, we synthesized biocompatible siMAPK1-loaded nanoparticles (NPs) and performed physicochemical characterizations for size, morphology, drug loading and release kinetics, using dynamic light scattering, electron microscopy and spectrophotometric analyses, respectively...
June 13, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28625810/evaluating-the-ototoxicity-of-a-anti-mrsa-peptide-kr-12-a2
#6
Chung Man Sung, Hong Chan Kim, Yong Beom Cho, Song Yub Shin, Chul Ho Jang
INTRODUCTION: Methicillin-Resistant Staphylococcus aureus (MRSA) is an emerging problem for the treatment of chronic suppurative otitis media, and also for pediatric tympanostomy tube otorrhea. To date, there are no effective topical antibiotic drugs to treat MRSA otorrhea. OBJECTIVE: In this study, we evaluated the ototoxicity of topical KR-12-a2 solution on the cochlea when it applied topically in the middle ear of guinea pigs. METHODS: The antimicrobial activity of KR-12-a2 against MRSA strains was examined by using the inhibition zone test...
May 31, 2017: Brazilian Journal of Otorhinolaryngology
https://www.readbyqxmd.com/read/28620284/electrophysiological-measurements-of-peripheral-vestibular-function-a-review-of-electrovestibulography
#7
REVIEW
Daniel J Brown, Christopher J Pastras, Ian S Curthoys
Electrocochleography (EcochG), incorporating the Cochlear Microphonic (CM), the Summating Potential (SP), and the cochlear Compound Action Potential (CAP), has been used to study cochlear function in humans and experimental animals since the 1930s, providing a simple objective tool to assess both hair cell (HC) and nerve sensitivity. The vestibular equivalent of ECochG, termed here Electrovestibulography (EVestG), incorporates responses of the vestibular HCs and nerve. Few research groups have utilized EVestG to study vestibular function...
2017: Frontiers in Systems Neuroscience
https://www.readbyqxmd.com/read/28620181/hair-bundles-of-cochlear-outer-hair-cells-are-shaped-to-minimize-their-fluid-dynamic-resistance
#8
Nikola Ciganović, Amanuel Wolde-Kidan, Tobias Reichenbach
The mammalian sense of hearing relies on two types of sensory cells: inner hair cells transmit the auditory stimulus to the brain, while outer hair cells mechanically modulate the stimulus through active feedback. Stimulation of a hair cell is mediated by displacements of its mechanosensitive hair bundle which protrudes from the apical surface of the cell into a narrow fluid-filled space between reticular lamina and tectorial membrane. While hair bundles of inner hair cells are of linear shape, those of outer hair cells exhibit a distinctive V-shape...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28618834/psychophysical-and-modeling-approaches-towards-determining-the-cochlear-phase-response-based-on-interaural-time-differences
#9
Hisaaki Tabuchi, Bernhard Laback
The cochlear phase response is often estimated by measuring masking of a tonal target by harmonic complexes with various phase curvatures. Maskers yielding most modulated internal envelope representations after passing the cochlear filter are thought to produce minimum masking, with fast-acting cochlear compression as the main contributor to that effect. Thus, in hearing-impaired (HI) listeners, reduced cochlear compression hampers estimation of the phase response using the masking method. This study proposes an alternative approach, based on the effect of the envelope modulation strength on the sensitivity to interaural time differences (ITDs)...
June 2017: Journal of the Acoustical Society of America
https://www.readbyqxmd.com/read/28614181/cochleovestibular-gene-transfer-in-neonatal-mice-by-canalostomy
#10
Jing-Ying Guo, Yu-Ying Liu, Teng-Fei Qu, Zhe Peng, Jing Xie, Guo-Peng Wang, Shu-Sheng Gong
Impairments of the inner ear result in sensorineural hearing loss and vestibular dysfunction in humans. A large proportion of these disorders are congenital, and involve both auditory and vestibular systems. Therefore, genetic interventions to correct deficits must be administered during early developmental stages. In this study, we evaluated inner ear gene transfer in neonatal mice by canalostomy using an adeno-associated virus serotype 8 (AAV8) vector. AAV8 with the green fluorescence protein (GFP) gene was inoculated into the inner ear of the neonatal mice through the posterior semicircular canal (canalostomy)...
June 13, 2017: Neuroreport
https://www.readbyqxmd.com/read/28603488/hypothesis-of-k-recycling-defect-is-not-a-primary-deafness-mechanism-for-cx26-gjb2-deficiency
#11
REVIEW
Hong-Bo Zhao
K(+)-recycling defect is a long-standing hypothesis for deafness mechanism of Connexin26 (Cx26, GJB2) mutations, which cause the most common hereditary deafness and are responsible for >50% of nonsyndromic hearing loss. The hypothesis states that Cx26 deficiency may disrupt inner ear gap junctions and compromise sinking and recycling of expelled K(+) ions after hair cell excitation, causing accumulation of K(+)-ions in the extracellular space around hair cells producing K(+)-toxicity, which eventually induces hair cell degeneration and hearing loss...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28598389/identification-of-a-novel-o-conotoxin-reveals-an-unusual-and-potent-inhibitor-of-the-human-%C3%AE-9%C3%AE-10-nicotinic-acetylcholine-receptor
#12
Shantong Jiang, Han-Shen Tae, Shaoqiong Xu, Xiaoxia Shao, David J Adams, Chunguang Wang
Conotoxins are a pool of disulfide-rich peptide neurotoxins produced by cone snails for predation and defense. They are a rich reservoir of novel ligands for ion channels, neurotransmitter receptors and transporters in the nervous system. In this study, we identified a novel conotoxin component, O-conotoxin GeXXVIIA, from the venom of Conus generalis. The native form of this component is a disulfide-linked homodimer of a 5-Cys-containing peptide. Surprisingly, our electrophysiological studies showed that, in comparison to the folded monomers, the linear peptide of this toxin had the highest inhibitory activity at the human α9α10 nicotinic acetylcholine receptor (nAChR), with an IC50 of 16...
June 9, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28584970/morphometric-evaluation-of-facial-and-vestibulocochlear-nerves-using-magnetic-resonance-imaging-comparison-of-meni%C3%A3-re-s-disease-ears-with-normal-hearing-ears
#13
Annika Henneberger, Birgit Ertl-Wagner, Maximilian Reiser, Robert Gürkov, Wilhelm Flatz
Loss of neural structures (such as hair cells or neurones within the spiral ganglion) has been proposed to be involved in Menière's disease (MD) (Spoendlin et al. Acta oto-laryngologica Supplementum 499:1-21, 1; Merchant et al. Eur Arch Oto-Rhino-Laryngol Off J Eur Feder Oto-Rhino-Laryngol Soc (EUFOS) Affil German Soc Oto-Rhino-Laryngol Head Neck Surg 252(2):63-75, 2; Tsuji et al. Ann Otol Rhinol Laryngol Suppl 81:26-31, 3; Kariya, Otol Neurotol Off Publ Am Otol Soc Am Neurotol Soc Eur Acad Otol Neurotol 28(8):1063-1068, 4; Megerian Laryngoscope 115(9):1525-1535, 5) but this has yet to be confirmed...
June 5, 2017: European Archives of Oto-rhino-laryngology
https://www.readbyqxmd.com/read/28580173/sesn2-gene-ablation-enhances-susceptibility-to-gentamicin-induced-hair-cell-death-via-modulation-of-ampk-mtor-signaling
#14
Eliane Ebnoether, Alessia Ramseier, Maurizio Cortada, Daniel Bodmer, Soledad Levano-Huaman
The process of gentamicin-induced hair cell damage includes the activation of oxidative stress processes. Sestrins, as stress-responsive proteins, protect cells against oxidative stress. Sestrins, particularly Sestrin-2, suppress excessive reactive oxygen species (ROS) accumulation and inhibit mammalian target of rapamycin complex 1 (mTORC1). Thus, we addressed the role of Sestrin-2 in the regulation of sensory hair cell survival after gentamicin exposure. Here, we show that Sestrins were expressed in the inner ear tissues, and Sestrin-2 immunolocalized in sensory hair cells and spiral ganglion (SG)...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28578877/progression-of-changes-in-the-sensorial-elements-of-the-cochlear-and-peripheral-vestibular-systems-the-otitis-media-continuum
#15
Rafael da Costa Monsanto, Patricia Schachern, Michael M Paparella, Sebahattin Cureoglu, Norma de Oliveira Penido
Our study aimed to evaluate pathologic changes in the cochlear (inner and outer hair cells and stria vascularis) and vestibular (vestibular hair cells, dark, and transitional cells) sensorial elements in temporal bones from donors who had otitis media. We studied 40 temporal bones from such donors, which were categorized in serous otitis media (SOM), serous-purulent otitis media (SPOM), mucoid/mucoid-purulent otitis media (MOM/MPOM), and chronic otitis media (COM); control group comprised 10 nondiseased temporal bones...
May 26, 2017: Hearing Research
https://www.readbyqxmd.com/read/28576729/afferent-synaptogenesis-between-ectopic-hair-cell-like-cells-and-neurites-of-spiral-ganglion-induced-by-atoh1-in-mammals-in-vitro
#16
Wen-Wei Luo, Rui Ma, Xiang Cheng, Xiao-Yu Yang, Zhao Han, Dong-Dong Ren, Ping Chen, Fang-Lu Chi, Juan-Mei Yang
Newly formed ectopic hair-cell-like cells (EHCLCs) induced by overexpression of atonal homolog 1 (Atoh1) in vitro were found to possess features of endogenous hair cells (HCs) in previous reports and in the present study. However, limited information is available regarding whether EHCLCs and native spiral ganglion neurons (SGNs) form afferent synapses, which are important for the restoration of hearing. In the current study, we focused on the afferent synaptogenesis between EHCLCs and SGN-derived dendrites...
May 31, 2017: Neuroscience
https://www.readbyqxmd.com/read/28573831/auditory-and-otologic-profile-of-alstr%C3%A3-m-syndrome-comprehensive-single-center-data-on-38-patients
#17
Spencer Lindsey, Carmen Brewer, Olga Stakhovskaya, Hung Jeffrey Kim, Chris Zalewski, Joy Bryant, Kelly A King, Jürgen K Naggert, William A Gahl, Jan D Marshall, Meral Gunay-Aygun
Alström syndrome (AS) is a rare autosomal recessive ciliopathy caused by mutations in the ALMS1 gene. Hallmark characteristics include childhood onset of severe retinal degeneration, sensorineural hearing loss, obesity, insulin-resistant diabetes, and cardiomyopathy. Here we comprehensively characterize the auditory and otologic manifestations in a prospective case series of 38 individuals, aged 1.7-37.9 years, with genetically confirmed AS. Hearing loss was preceded by retinal dystrophy in all cases, and had an average age of detection of 7...
June 1, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28572758/activation-of-chk1-in-supporting-cells-indirectly-promotes-hair-cell-survival
#18
Azadeh Jadali, Yu-Lan M Ying, Kelvin Y Kwan
The sensory hair cells of the inner ear are exquisitely sensitive to ototoxic insults. Loss of hair cells after exposure to ototoxic agents causes hearing loss. Chemotherapeutic agents such as cisplatin causes hair cell loss. Cisplatin forms DNA mono-adducts as well as intra- and inter-strand DNA crosslinks. DNA cisplatin adducts are repaired through the DNA damage response. The decision between cell survival and cell death following DNA damage rests on factors that are involved in determining damage tolerance, cell survival and apoptosis...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28560432/otoprotective-effects-of-ethosuximide-in-nod-ltj-mice-with-age-related-hearing-loss
#19
Lu Sang, Tihua Zheng, Lingqian Min, Xiaolin Zhang, Xiufang Ma, Shami Entenman, Yipeng Su, Qingyin Zheng
Despite long-term efforts to elucidate the mechanisms responsible for age-related hearing loss (AHL), there is currently no available treatment strategy able to provide a cure. Apoptotic cell death, including that of hair cells and spiral ganglion neurons (SGNs) in the cochlea has been proposed to be the classic theory behind the development of AHL. As calcium signaling plays key roles in signal transduction in apoptosis, in this study, we selected ethosuximide, which is able to block T-type calcium (Ca2+ion) channels, suppressing Ca2+...
May 26, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28552523/progressive-age-dependence-and-frequency-difference-in-the-effect-of-gap-junctions-on-active-cochlear-amplification-and-hearing
#20
Liang Zong, Jin Chen, Yan Zhu, Hong-Bo Zhao
Mutations of Connexin 26 (Cx26, GJB2), which is a predominant gap junction isoform in the cochlea, can induce high incidence of nonsyndromic hearing loss. We previously found that targeted-deletion of Cx26 in supporting Deiters cells and outer pillar cells in the cochlea can influence outer hair cell (OHC) electromotility and reduce active cochlear amplification leading to hearing loss, even though there are no gap junction connexin expressions in the auditory sensory hair cells. Here, we further report that hearing loss and the reduction of active amplification in the Cx26 targeted-deletion mice are progressive and different at high and low frequency regions, first occurring in the high frequency region and then progressively extending to the middle and low frequency regions with mouse age increased...
May 25, 2017: Biochemical and Biophysical Research Communications
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