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1.
J Laryngol Otol ; 134(6): 509-518, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32508296

RESUMO

OBJECTIVE: To determine the prevalence and distribution of inner-ear malformations in congenital single-sided deafness cases, as details of malformation type are crucial for disease prognosis and management. METHODS: A retrospective study was conducted of 90 patients aged under 16 years with congenital single-sided deafness. Radiological findings were evaluated using computed tomography and magnetic resonance imaging. Inner-ear malformations were identified and cochlear nerve status was determined in affected ears. RESULTS: Out of 90 ears, 42 (46.7 per cent) were found to have inner-ear malformation. Isolated cochlear aperture stenosis was the most common anomaly (n = 18, 20 per cent), followed by isolated cochlear aperture atresia (n = 11, 12.2 per cent) and cochlear hypoplasia (n = 7, 7.8 per cent). Cochlear nerve deficiency was encountered in 41 ears (45.6 per cent). The internal auditory canal was also stenotic in 49 ears (54.4 per cent). CONCLUSION: Inner-ear malformations, especially cochlear aperture anomalies, are involved in the aetiology of single-sided deafness more than expected. The cause of single-sided deafness differs greatly between congenital and adult-onset cases. All children with single-sided deafness should undergo radiological evaluation, as the prognosis and management, as well as the aetiology, may be significantly influenced by inner-ear malformation type.


Assuntos
Cóclea/patologia , Surdez/etiologia , Orelha Interna/anormalidades , Doenças do Labirinto/congênito , Adolescente , Criança , Pré-Escolar , Cóclea/anormalidades , Cóclea/inervação , Nervo Coclear/anormalidades , Nervo Coclear/fisiopatologia , Constrição Patológica/patologia , Surdez/diagnóstico , Orelha Interna/diagnóstico por imagem , Orelha Interna/patologia , Feminino , Perda Auditiva Neurossensorial/congênito , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/epidemiologia , Humanos , Lactente , Doenças do Labirinto/epidemiologia , Imagem por Ressonância Magnética/métodos , Masculino , Prevalência , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Doenças do Nervo Vestibulococlear/congênito , Doenças do Nervo Vestibulococlear/epidemiologia
2.
BMJ ; 369: m718, 2020 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-32349978

RESUMO

Head and neck structures govern the vital functions of breathing and swallowing. Additionally, these structures facilitate our sense of self through vocal communication, hearing, facial animation, and physical appearance. Loss of these functions can lead to loss of life or greatly affect quality of life. Regenerative medicine is a rapidly developing field that aims to repair or replace damaged cells, tissues, and organs. Although the field is largely in its nascence, regenerative medicine holds promise for improving on conventional treatments for head and neck disorders or providing therapies where no current standard exists. This review presents milestones in the research of regenerative medicine in head and neck surgery.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Otolaringologia/tendências , Procedimentos Cirúrgicos Reconstrutivos/tendências , Medicina Regenerativa/tendências , Tecidos Suporte , Bioengenharia , Transplante de Células/métodos , Transplante de Células/tendências , Cóclea , Cartilagem da Orelha , Ossos Faciais , Humanos , Laringe , Cartilagens Nasais , Procedimentos Cirúrgicos Reconstrutivos/métodos , Glândulas Salivares , Crânio , Engenharia Tecidual/métodos , Engenharia Tecidual/tendências , Traqueia , Membrana Timpânica
3.
PLoS Genet ; 16(4): e1008643, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32294086

RESUMO

Hereditary hearing loss is challenging to diagnose because of the heterogeneity of the causative genes. Further, some genes involved in hereditary hearing loss have yet to be identified. Using whole-exome analysis of three families with congenital, severe-to-profound hearing loss, we identified a missense variant of SLC12A2 in five affected members of one family showing a dominant inheritance mode, along with de novo splice-site and missense variants of SLC12A2 in two sporadic cases, as promising candidates associated with hearing loss. Furthermore, we detected another de novo missense variant of SLC12A2 in a sporadic case. SLC12A2 encodes Na+, K+, 2Cl- cotransporter (NKCC) 1 and plays critical roles in the homeostasis of K+-enriched endolymph. Slc12a2-deficient mice have congenital, profound deafness; however, no human variant of SLC12A2 has been reported as associated with hearing loss. All identified SLC12A2 variants mapped to exon 21 or its 3'-splice site. In vitro analysis indicated that the splice-site variant generates an exon 21-skipped SLC12A2 mRNA transcript expressed at much lower levels than the exon 21-included transcript in the cochlea, suggesting a tissue-specific role for the exon 21-encoded region in the carboy-terminal domain. In vitro functional analysis demonstrated that Cl- influx was significantly decreased in all SLC12A2 variants studied. Immunohistochemistry revealed that SLC12A2 is located on the plasma membrane of several types of cells in the cochlea, including the strial marginal cells, which are critical for endolymph homeostasis. Overall, this study suggests that variants affecting exon 21 of the SLC12A2 transcript are responsible for hereditary hearing loss in humans.


Assuntos
Perda Auditiva Neurossensorial/congênito , Perda Auditiva Neurossensorial/genética , Mutação , Domínios Proteicos/genética , Membro 2 da Família 12 de Carreador de Soluto/química , Membro 2 da Família 12 de Carreador de Soluto/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Cloretos/metabolismo , Cóclea/metabolismo , Cóclea/patologia , Surdez/congênito , Surdez/genética , Éxons/genética , Feminino , Expressão Gênica , Células HEK293 , Humanos , Lactente , Macaca fascicularis , Masculino , Linhagem , Processamento de RNA , RNA Mensageiro/análise , RNA Mensageiro/genética , Membro 2 da Família 12 de Carreador de Soluto/metabolismo
4.
PLoS One ; 15(3): e0230233, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32196513

RESUMO

In spite of its acoustic diversity, the speech signal presents statistical regularities that can be exploited by biological or artificial systems for efficient coding. Independent Component Analysis (ICA) revealed that on small time scales (∼ 10 ms), the overall structure of speech is well captured by a time-frequency representation whose frequency selectivity follows the same power law in the high frequency range 1-8 kHz as cochlear frequency selectivity in mammals. Variations in the power-law exponent, i.e. different time-frequency trade-offs, have been shown to provide additional adaptation to phonetic categories. Here, we adopt a parametric approach to investigate the variations of the exponent at a finer level of speech. The estimation procedure is based on a measure that reflects the sparsity of decompositions in a set of Gabor dictionaries whose atoms are Gaussian-modulated sinusoids. We examine the variations of the exponent associated with the best decomposition, first at the level of phonemes, then at an intra-phonemic level. We show that this analysis offers a rich interpretation of the fine-grained statistical structure of speech, and that the exponent values can be related to key acoustic properties. Two main results are: i) for plosives, the exponent is lowered by the release bursts, concealing higher values during the opening phases; ii) for vowels, the exponent is bound to formant bandwidths and decreases with the degree of acoustic radiation at the lips. This work further suggests that an efficient coding strategy is to reduce frequency selectivity with sound intensity level, congruent with the nonlinear behavior of cochlear filtering.


Assuntos
Fala/fisiologia , Estimulação Acústica/métodos , Cóclea/fisiologia , Implantes Cocleares , Humanos , Fonética , Acústica da Fala , Percepção da Fala/fisiologia
5.
Int. arch. otorhinolaryngol. (Impr.) ; 24(1): 47-52, Jan.-Mar. 2020. graf
Artigo em Inglês | LILACS | ID: biblio-1090559

RESUMO

Abstract Introduction Cisplatin damages the auditory system and is related to the generation of free radicals. Glutathione peroxidase is an endogenous free radicals remover. Objective To investigate the mechanisms involved in otoprotection by N-acetylcys- teine through the expression of glutathione peroxidase in outer hair cells from rats treated with cisplatin. Methods Male Wistar rats were intraperitoneally injected with cisplatin (8 mg/Kg) and/or received oral administration by gavage of N-acetylcysteine (300 mg/Kg) for 3 consecutive days. On the 4th day, the animals were euthanized and beheaded. The tympanic bullae were removed and prepared for scanning electron microscopy and Results Among the groups exposed to ototoxic doses of cisplatin, there was an increase in glutathione peroxidase immunostaining in two groups, the one exposed to cisplatin alone, and the group exposed to both cisplatin and N-acetylcysteine. Conclusion The expression of glutathione peroxidase in the outer hair cells of rats exposed to cisplatin showed the synthesis of this enzyme under cellular toxicity conditions.


Assuntos
Animais , Masculino , Acetilcisteína/uso terapêutico , Depuradores de Radicais Livres/uso terapêutico , Cisplatino/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Antineoplásicos/toxicidade , Acetilcisteína/metabolismo , Acetilcisteína/farmacologia , Microscopia Eletrônica de Varredura , Potenciais Evocados Auditivos do Tronco Encefálico , Depuradores de Radicais Livres/metabolismo , Depuradores de Radicais Livres/farmacologia , Imunofluorescência , Cisplatino/uso terapêutico , Ratos Wistar , Cóclea/anatomia & histologia , Cóclea/efeitos dos fármacos , Radicais Livres , Glutationa Peroxidase/metabolismo , Perda Auditiva Neurossensorial/prevenção & controle
6.
Proc Natl Acad Sci U S A ; 117(7): 3828-3838, 2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32015128

RESUMO

Exposure to loud sound damages the postsynaptic terminals of spiral ganglion neurons (SGNs) on cochlear inner hair cells (IHCs), resulting in loss of synapses, a process termed synaptopathy. Glutamatergic neurotransmission via α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type receptors is required for synaptopathy, and here we identify a possible involvement of GluA2-lacking Ca2+-permeable AMPA receptors (CP-AMPARs) using IEM-1460, which has been shown to block GluA2-lacking AMPARs. In CBA/CaJ mice, a 2-h exposure to 100-dB sound pressure level octave band (8 to 16 kHz) noise results in no permanent threshold shift but does cause significant synaptopathy and a reduction in auditory brainstem response (ABR) wave-I amplitude. Chronic intracochlear perfusion of IEM-1460 in artificial perilymph (AP) into adult CBA/CaJ mice prevented the decrease in ABR wave-I amplitude and the synaptopathy relative to intracochlear perfusion of AP alone. Interestingly, IEM-1460 itself did not affect the ABR threshold, presumably because GluA2-containing AMPARs can sustain sufficient synaptic transmission to evoke low-threshold responses during blockade of GluA2-lacking AMPARs. On individual postsynaptic densities, we observed GluA2-lacking nanodomains alongside regions with robust GluA2 expression, consistent with the idea that individual synapses have both CP-AMPARs and Ca2+-impermeable AMPARs. SGNs innervating the same IHC differ in their relative vulnerability to noise. We found local heterogeneity among synapses in the relative abundance of GluA2 subunits that may underlie such differences in vulnerability. We propose a role for GluA2-lacking CP-AMPARs in noise-induced cochlear synaptopathy whereby differences among synapses account for differences in excitotoxic susceptibility. These data suggest a means of maintaining normal hearing thresholds while protecting against noise-induced synaptopathy, via selective blockade of CP-AMPARs.


Assuntos
Cálcio/metabolismo , Cóclea/metabolismo , Perda Auditiva Provocada por Ruído/metabolismo , Ruído/efeitos adversos , Receptores de AMPA/metabolismo , Sinapses/metabolismo , Animais , Potenciais Evocados Auditivos do Tronco Encefálico , Audição , Perda Auditiva Provocada por Ruído/etiologia , Perda Auditiva Provocada por Ruído/genética , Perda Auditiva Provocada por Ruído/fisiopatologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos CBA , Receptores de AMPA/genética
7.
Ideggyogy Sz ; 73(1-2): 53-59, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32057205

RESUMO

Background - Several cochlear implant recipients experience functionality loss due to electrode array mal-positioning. The application of delicate perimodiolar electrodes has many electrophysiological advantages, however, these profiles may be more susceptible to tip fold-over. Purpose - The prompt realization of such complication following electrode insertion would be auspicious, thus the electrode could be possibly repositioned during the same surgical procedure. Methods - The authors present three tip fold-over cases, experienced throughout their work with Slim Modiolar Electrode implants. Implantations were performed through the round window approach, by a skilled surgeon. Standard intraoperative measurements (electric integrity, neural response telemetry, and electrical stapedial reflex threshold tests) were successfully completed. The electrode position was controlled by conventional radiography on the first postoperative day. Results - Tip fold-over was not tactilely sensated by the surgeon. Our subjects revealed normal intraoperative telemetry measurements, only the postoperative imaging showed the tip fold-over. Due to the emerging adverse perception of constant beeping noise, the device was replaced by a CI512 implant after 6 months in one case. In the two remaining cases, the electrode array was reloaded into a back-up sheath, and reinserted into the scala tympani successfully through an extended round window approach. Discussion - Future additional studies using the spread of excitation or electric field imaging may improve test reliability. As all of these measurements are still carried out following electrode insertion, real-time identification, unfortunately, remains questionable. Conclusion - Tip fold-over could be reliably identified by conventional X-ray imaging. By contrast, intraoperative electrophysiology was not sufficiently sensitive to reveal it.


Assuntos
Implante Coclear , Implantes Cocleares , Eletrodos Implantados , Cóclea , Humanos , Reprodutibilidade dos Testes , Rampa do Tímpano
9.
HNO ; 68(4): 272-277, 2020 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-31915883

RESUMO

BACKGROUND: Hearing loss is frequently induced by occupational noise exposure and leads to rising hearing thresholds as well as reduced otoacoustic emissions (OAE), mostly caused by metabolic hair cell decompensation. OBJECTIVE: Primary endpoint is the increase in average pure tone thresholds after noise exposure, secondary endpoints are loss of distortion product and click-evoked OAE as well as reduction of their contralateral suppression. PARTICIPANTS AND METHODS: The present study design describes the verification of the anti-oxidant and neuroprotective properties of EGb 761® by evaluation of cochlear protection from noise impact as well as its safety and tolerance in 202 healthy male participants distributed equally to verum and placebo groups in a double-blind manner. Participants were assessed, medicated, exposed to noise, and then examined at timepoints up to 10 min and 4 weeks thereafter. CONCLUSION: This summary of the verification study protocol highlights the complexity of diligent and precise planning according to the European Medicines Agency criteria for controlled trials (EudraCT). Key points are the intervention rationale, definitions of in- and exclusion criteria, estimation of subject numbers, and examination method setting in terms of optimum endpoint description.


Assuntos
Perda Auditiva Provocada por Ruído , Extratos Vegetais , Audiometria de Tons Puros , Limiar Auditivo , Cóclea , Método Duplo-Cego , Perda Auditiva Provocada por Ruído/terapia , Humanos , Masculino , Emissões Otoacústicas Espontâneas , Extratos Vegetais/uso terapêutico , Estudos Prospectivos
10.
FASEB J ; 34(1): 1136-1149, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31914662

RESUMO

Usher syndrome (USH) is the most frequent form of combined hereditary deafness-blindness, characterized by hearing loss and retinitis pigmentosa, with or without vestibular dysfunction. PDZD7 is a PDZ domain-containing scaffold protein that was suggested to be a USH modifier and a contributor to digenic USH. In the inner ear hair cells, PDZD7 localizes at the ankle region of the stereocilia and constitutes the so-called ankle-link complex together with three other USH proteins Usherin, WHRN, and ADGRV1. PDZD7 gene is subjected to alternative splicing, which gives rise to two types of PDZD7 isoforms, namely the long and short isoforms. At present, little is known which specific isoform is involved in ankle-link formation and stereocilia development. In this work, we showed that PDZD7 long isoform, but not short isoforms, localizes at the ankle region of the stereocilia. Moreover, we established Pdzd7 mutant mice by introducing deletions into exon 14 of the Pdzd7 gene, which causes potential premature translational stop in the long isoform but leaves short isoforms unaffected. We found that lack of PDZD7 long isoform affects the localization of other ankle-link complex components in the stereocilia. Consequently, Pdzd7 mutant mice showed stereocilia development deficits and hearing loss as well as reduced mechanotransduction (MET) currents, suggesting that PDZD7 long isoform is indispensable for hair cells. Furthermore, by performing yeast two-hybrid screening, we identified a PDZD7 long isoform-specific binding partner PIP5K1C, which has been shown to play important roles in hearing and might participate in the function and/or transportation of PDZD7.


Assuntos
Proteínas de Transporte/química , Proteínas de Transporte/genética , Perda Auditiva/genética , Síndromes de Usher/genética , Processamento Alternativo , Animais , Cóclea/metabolismo , Modelos Animais de Doenças , Éxons , Feminino , Deleção de Genes , Células HEK293 , Células Ciliadas Auditivas , Humanos , Masculino , Mecanotransdução Celular , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Varredura , Mutação , Isoformas de Proteínas , Estereocílios/química
11.
PLoS One ; 15(1): e0227978, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31961907

RESUMO

AIM: Occupational exposure to styrene has been shown to be associated with an increased probability of developing hearing loss. However, the sites of lesions in the auditory system in humans remain unknown. The aim of this study was to investigate the possible adverse effects of styrene exposure on the cochlea of human subjects. DESIGN: The hearing function of 98 styrene-exposed male workers from the glass fibre-reinforced plastics industry (mean concentration of 55 mg/m3) was evaluated bilaterally using pure-tone audiometry (1000-16000 Hz), distortion product otoacoustic emissions (DPOAEs), and auditory brainstem response (ABR). The results were compared to a group of 111 male workers exposed to noise (above 85 dBA) and 70 male white-collar workers exposed to neither noise nor solvents. Age and noise exposure levels were accounted for as confounding variables in all statistical models. RESULTS: Styrene exposure was significantly associated with poorer pure-tone thresholds (1-8 kHz), lower DPOAE amplitudes (5-6 kHz), and shorter wave V latencies in both ears compared to control-group subjects. Similar results were found among noise-exposed subjects. A further analysis with wave V latency showed that styrene-exposed subjects showed significantly shorter latencies than expected according to normative data. These results suggest that occupational exposure to styrene at moderate concentrations is associated with cochlear dysfunction, at least at high frequencies. DPOAEs may be considered a valuable diagnostic tool in hearing conservation programs in workers exposed to styrene.


Assuntos
Cóclea/fisiopatologia , Perda Auditiva , Exposição Ocupacional/efeitos adversos , Emissões Otoacústicas Espontâneas , Estireno/toxicidade , Adulto , Limiar Auditivo , Perda Auditiva/diagnóstico , Perda Auditiva/fisiopatologia , Perda Auditiva/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Ruído/efeitos adversos , Adulto Jovem
12.
HNO ; 68(Suppl 1): 25-32, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31598773

RESUMO

BACKGROUND: Incomplete partition type III (IP III) is defined by a missing lamina cribrosa between the cochlea and the internal auditory canal (IAC). Cochlear implantation (CI) may result in an insertion of the electrode array into the IAC. The aim of this study is to evaluate CI surgery protocols, long-term audiological outcome, mapping and electrophysiological data after CI in IP III patients. MATERIALS AND METHODS: Nine IP III patients were implanted with perimodiolar electrode arrays between 1999 and 2014; eight of them were included in this study. We evaluated mapping data, stapedius reflexes, electrode impedances and ECAP thresholds. We matched them with 3 CI patients each with normal cochlear morphology regarding sex, age, side, implant type and surgical date. Speech discrimination was evaluated with the Oldenburger sentence test for adults, Göttingen audiometric speech test for children and the Freiburger monosyllabic word test. RESULTS: 3 years after CI IP III patients showed a significant increase in pulse width, calculated electric load and electrode impedances in basal electrodes. Intraoperative electrically-evoked stapedius reflexes could be measured in all patients. Speech recognition scores were lower than average scores for matched patients, but without statistical significance. CONCLUSIONS: The significant increase of pulse width, electric load and electrode impedances of basal electrodes over time seem to be characteristic for IP III patients probably occurring due to fibrosis and neurodegeneration of the cochlear nerve. The long term audiological results are stable. Intraoperative imaging and stapedius reflexes are highly recommended to control the right position of the electrode array.


Assuntos
Cóclea , Implante Coclear , Implantes Cocleares , Adulto , Criança , Cóclea/patologia , Cóclea/fisiopatologia , Nervo Coclear , Humanos , Reflexo Acústico
13.
Cell Mol Life Sci ; 77(4): 619-635, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31522250

RESUMO

Estrogen is the major female hormone involved in reproductive functions, but it also exerts a variety of additional roles in non-reproductive organs. In this review, we highlight the preclinical and clinical studies that have pointed out sex differences and estrogenic influence on audition. We also describe the experimental evidences supporting a protective role of estrogen towards acquired forms of hearing loss. Although a high level of endogenous estrogen is associated with a better hearing function, hormonal treatments at menopause have provided contradictory outcomes. The various factors that are likely to explain these discrepancies include the treatment regimen as well as the hormonal status and responsiveness of the patients. The complexity of estrogen signaling is being untangled and many downstream effectors of its genomic and non-genomic actions have been identified in other systems. Based on these advances and on the common physio-pathological events that underlie age-related, drug or noise-induced hearing loss, we discuss potential mechanisms for their protective actions in the cochlea.


Assuntos
Estrogênios/metabolismo , Audição , Animais , Cóclea/metabolismo , Cóclea/patologia , Surdez/etiologia , Surdez/metabolismo , Surdez/patologia , Feminino , Humanos , Masculino , Receptores Estrogênicos/metabolismo , Caracteres Sexuais , Fatores Sexuais , Transdução de Sinais
14.
Cell Mol Life Sci ; 77(7): 1401-1419, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31485717

RESUMO

Foxg1 is one of the forkhead box genes that are involved in morphogenesis, cell fate determination, and proliferation, and Foxg1 was previously reported to be required for morphogenesis of the mammalian inner ear. However, Foxg1 knock-out mice die at birth, and thus the role of Foxg1 in regulating hair cell (HC) regeneration after birth remains unclear. Here we used Sox2CreER/+ Foxg1loxp/loxp mice and Lgr5-EGFPCreER/+ Foxg1loxp/loxp mice to conditionally knock down Foxg1 specifically in Sox2+ SCs and Lgr5+ progenitors, respectively, in neonatal mice. We found that Foxg1 conditional knockdown (cKD) in Sox2+ SCs and Lgr5+ progenitors at postnatal day (P)1 both led to large numbers of extra HCs, especially extra inner HCs (IHCs) at P7, and these extra IHCs with normal hair bundles and synapses could survive at least to P30. The EdU assay failed to detect any EdU+ SCs, while the SC number was significantly decreased in Foxg1 cKD mice, and lineage tracing data showed that much more tdTomato+ HCs originated from Sox2+ SCs in Foxg1 cKD mice compared to the control mice. Moreover, the sphere-forming assay showed that Foxg1 cKD in Lgr5+ progenitors did not significantly change their sphere-forming ability. All these results suggest that Foxg1 cKD promotes HC regeneration and leads to large numbers of extra HCs probably by inducing direct trans-differentiation of SCs and progenitors to HCs. Real-time qPCR showed that cell cycle and Notch signaling pathways were significantly down-regulated in Foxg1 cKD mice cochlear SCs. Together, this study provides new evidence for the role of Foxg1 in regulating HC regeneration from SCs and progenitors in the neonatal mouse cochlea.


Assuntos
Transdiferenciação Celular , Cóclea/citologia , Fatores de Transcrição Forkhead/deficiência , Células Ciliadas Auditivas/citologia , Células Labirínticas de Suporte/citologia , Proteínas do Tecido Nervoso/deficiência , Animais , Animais Recém-Nascidos , Contagem de Células , Linhagem da Célula , Proliferação de Células , Sobrevivência Celular , Cóclea/inervação , Fatores de Transcrição Forkhead/metabolismo , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Células Ciliadas Auditivas/ultraestrutura , Células Labirínticas de Suporte/ultraestrutura , Mecanotransdução Celular , Camundongos Transgênicos , Proteínas do Tecido Nervoso/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Transdução de Sinais/genética , Células-Tronco/metabolismo , Sinapses/metabolismo
15.
Braz J Otorhinolaryngol ; 86(1): 30-37, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30268784

RESUMO

INTRODUCTION: Ototoxicity is a health problem appearing after powerful treatments in serious health conditions. It is sometimes inevitable when treatment of the serious disease is required. Cisplatin is an antineoplastic agent which was investigated previously to reveal increased nitrogen and reactive oxygen radicals that damages hair cells, resulting in ototoxicity. N-acetylcysteine, previously shown to decrease ototoxicity caused by different agents, is known to be a powerful in vitro antioxidant. Probably N-acetylcysteine, in addition to its antioxidant effect, blocks a cascade where reactive oxygen species result in apoptosis in the cochlea. OBJECTIVES: The possible preventive effect of N-acetylcysteine in cisplatin ototoxicity was studied with auditory brain stem responses, otoacoustic emissions, and histopathological investigation of the cochlea in a scanning electron microscopy. METHODS: This study was conducted on 21 Wistar Albino rats in four groups. 1mL/kg/day three times in total intraperitoneal (i.p.) Saline (n=5), 500mg/kg/day i.p. three times in total N-acetylcysteine (n=5), i.p. 15mg/kg cisplatin alone (single dose) (n=5) and i.p. 15mg/kg cisplatin plus 500mg/kg/day N-acetylcysteine (n=6) were administered. The rats were anesthetized to study the hearing tests before and after the experiment. The rats were sacrificed to investigate the cochleas by scanning electron microscopy. RESULTS: Auditory brain stem responses and otoacoustic emissions values were attenuated in the cisplatin group. The group that received N-acetylcysteine in addition to cisplatin had better auditory brain stem responses thresholds and otoacoustic emissions. The samples obtained from the cisplatin group showed surface irregularities, degeneration areas, and total or partial severe stereocilia losses. The changes were milder in the cisplatin+N-acetylcysteine group. CONCLUSION: Cisplatin ototoxicity can be detected by auditory brain stem responses and otoacoustic emissions testing in rats. N-acetylcysteine may protect the cochlear cells from histopathological changes. We concluded that N-acetylcysteine given 4h after cisplatin injection has a potential otoprotective effect against cisplatin ototoxicity. which suggests it could be used in clinical trials.


Assuntos
Acetilcisteína/administração & dosagem , Antineoplásicos/efeitos adversos , Antioxidantes/administração & dosagem , Cisplatino/efeitos adversos , Ototoxicidade/etiologia , Substâncias Protetoras/administração & dosagem , Acetilcisteína/farmacologia , Animais , Antioxidantes/farmacologia , Apoptose , Cóclea/efeitos dos fármacos , Cóclea/patologia , Modelos Animais de Doenças , Potenciais Evocados Auditivos do Tronco Encefálico , Células Ciliadas Auditivas Externas/efeitos dos fármacos , Células Ciliadas Auditivas Externas/patologia , Testes Auditivos , Masculino , Microscopia Eletrônica de Varredura , Ototoxicidade/prevenção & controle , Substâncias Protetoras/farmacologia , Ratos Wistar , Razão Sinal-Ruído , Estereocílios/efeitos dos fármacos , Estereocílios/patologia
16.
Braz J Otorhinolaryngol ; 86(2): 222-227, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30797727

RESUMO

INTRODUCTION: The use of electron microscopy in the study of the inner ear has allowed us to observe minute details of the hair cells, especially in ototoxicity studies; however, the preparation of this material is a difficult and delicate task. In an attempt to simplify the handling of these materials, two agents, toluidine blue and ethylenediamine tetra-acetic acid were tested, in addition to the elimination of osmium tetroxide during the preparation of albino guinea pig cochleae. We also tested the applicability of these methodologies in an ototoxicity protocol. OBJECTIVE: To verify the quality of the images obtained with and without the use of ethylenediamine tetra-acetic acid, toluidine blue and osmium tetroxide in the preparation of cochleae of albino guinea pigs for the scanning electron microscopy. METHODS: Three groups of cochleae were used. In Group 1, 10 cochleae were prepared with the usual methodology, dissecting the optical capsule without decalcification and using osmium tetroxide as a post-fixative agent. In Group 2, we prepared 10 cochleae decalcified with ethylenediamine tetra-acetic acid, injecting toluidine blue in the endolymphatic space to facilitate the identification of the organ of Corti. In Group 3, we used 4 cochleae of guinea pigs that received 3 doses of cisplatin (7.5mg/kg, D1-D5-D6), two prepared according to the methodology used in Group 1 and two with that used in Group 2. Scanning electron microscopy images were obtained from the organ of Corti region of the basal turn of each cochlea. RESULTS: The organ of Corti was more easily identified with the use of toluidine blue. The dissection of the cochlea was more accurate in the decalcified cochleae. The quality of the images and the preservation of the organ of Corti obtained with the two methodologies were similar. CONCLUSION: The proposed modifications resulted in images of similar quality as those observed using the traditional methodology.


Assuntos
Cisplatino/toxicidade , Cóclea/efeitos dos fármacos , Cóclea/ultraestrutura , Animais , Ácido Edético/administração & dosagem , Feminino , Cobaias , Células Ciliadas Auditivas/efeitos dos fármacos , Células Ciliadas Auditivas/ultraestrutura , Microscopia Eletrônica de Varredura , Órgão Espiral/efeitos dos fármacos , Órgão Espiral/ultraestrutura , Tetróxido de Ósmio/administração & dosagem , Cloreto de Tolônio/administração & dosagem
17.
Otolaryngol Clin North Am ; 53(1): 87-102, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31677740

RESUMO

Cochlear implant is the first approved cranial nerve stimulator that works by directly stimulating the cochlear nerve. The medical and societal impact of this revolutionary device cannot be understated. This article reviews the evolving indications for cochlear implant, patient assessment, surgical approach, and outcomes for pediatric and adult cochlear implant that demonstrate its impact. Future concepts in cochlear implant are introduced briefly. This article covers a breadth of information; however, it is not intended be entirely comprehensive. Rather, it should serve as a foundation for understanding cochlear implant.


Assuntos
Implante Coclear/métodos , Implantes Cocleares , Perda Auditiva Neurossensorial/terapia , Adulto , Limiar Auditivo , Criança , Cóclea/patologia , Cóclea/cirurgia , Nervo Coclear/fisiologia , Humanos
18.
Synapse ; 74(1): e22128, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31403743

RESUMO

The auditory system has an extensive efferent innervation, which contributes to processes of control and regulation of the afferent input. The expression of receptors to various neurotransmitters and neuropeptides in the inner ear has been described, among which endogenous opioid receptors are found. The role of opioid receptors in the cochlea is not yet fully defined, it has been reported that opioid agonists and antagonists modulate the response to auditory stimuli and in clinical practice, multiple cases have been reported in which the consumption of opioid derivatives induce sensorineural hearing loss. In this work, we evaluated the effects of acute treatment with morphine, fentanyl, tramadol, and naloxone, in the auditory brain stem potentials (ABR), the compound action potential (CAP), and distortion products otacoustic emissions (DPOAE), across a wide range of stimulus frequencies and amplitudes. Adult Long-Evans rats of the strain CII/ZV weighing 180-220 g were used. For the ABR recording drugs were administered intraperitoneally or intravenously. For the CAP and DPOAE drugs were applied by direct perfusion in the middle ear. The opioid agonists produced a consistent increase in the amplitude of the PI component of the ABR and of the N1-P1 amplitude of the CAP. Naloxone produced no significant changes in the ABR and a reduction of the CAP N1-P1 amplitude. Also, opioid agonists induced a decrease in the amplitude of the DPOAE. These results show that the opioid receptor activation modulates both the afferent response at both the afferent response to acoustic stimuli, and also at the cochlear mechanics as revealed by DPOAE changes. These results present a significant step in understanding how opioid modulation of auditory responses may contribute to the auditory processing and to sensorineural hearing loss produced by opioids.


Assuntos
Potenciais de Ação/efeitos dos fármacos , Analgésicos Opioides/farmacologia , Cóclea/efeitos dos fármacos , Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Antagonistas de Entorpecentes/farmacologia , Emissões Otoacústicas Espontâneas/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Cóclea/fisiologia , Fentanila/farmacologia , Morfina/farmacologia , Naloxona/farmacologia , Emissões Otoacústicas Espontâneas/fisiologia , Ratos , Ratos Long-Evans , Tramadol/farmacologia
19.
Physiol Rev ; 100(1): 103-144, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31373863

RESUMO

In recent years, sensory neuroscientists have made major efforts to dissect the structure and function of ribbon synapses which process sensory information in the eye and ear. This review aims to summarize our current understanding of two key aspects of ribbon synapses: 1) their mechanisms of exocytosis and endocytosis and 2) their molecular anatomy and physiology. Our comparison of ribbon synapses in the cochlea and the retina reveals convergent signaling mechanisms, as well as divergent strategies in different sensory systems.


Assuntos
Cóclea/fisiologia , Retina/fisiologia , Sinapses/fisiologia , Animais , Endocitose , Exocitose , Humanos , Transmissão Sináptica
20.
Nat Commun ; 10(1): 5530, 2019 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-31797926

RESUMO

The adult mammalian inner ear lacks the capacity to divide or regenerate. Damage to inner ear generally leads to permanent hearing loss in humans. Here, we present that reprogramming of the adult inner ear induces renewed proliferation and regeneration of inner ear cell types. Co-activation of cell cycle activator Myc and inner ear progenitor gene Notch1 induces robust proliferation of diverse adult cochlear sensory epithelial cell types. Transient MYC and NOTCH activities enable adult supporting cells to respond to transcription factor Atoh1 and efficiently transdifferentiate into hair cell-like cells. Furthermore, we uncover that mTOR pathway participates in MYC/NOTCH-mediated proliferation and regeneration. These regenerated hair cell-like cells take up the styryl dye FM1-43 and are likely to form connections with adult spiral ganglion neurons, supporting that Myc and Notch1 co-activation is sufficient to reprogram fully mature supporting cells to proliferate and regenerate hair cell-like cells in adult mammalian auditory organs.


Assuntos
Proliferação de Células/fisiologia , Cóclea/fisiologia , Células Ciliadas Auditivas Internas/fisiologia , Regeneração/fisiologia , Animais , Proliferação de Células/genética , Cóclea/citologia , Cóclea/metabolismo , Orelha Interna/citologia , Orelha Interna/metabolismo , Orelha Interna/fisiologia , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Células Epiteliais/fisiologia , Gânglios Sensitivos/citologia , Gânglios Sensitivos/metabolismo , Gânglios Sensitivos/fisiologia , Regulação da Expressão Gênica , Células Ciliadas Auditivas Internas/metabolismo , Humanos , Camundongos , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Receptor Notch1/genética , Receptor Notch1/metabolismo , Regeneração/genética
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