Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 16 de 16
Filtrar
1.
J Adv Res ; 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38030129

RESUMO

INTRODUCTION: Cisplatin is a life-saving anticancer compound used to treat multiple solid malignant tumors, while it causes permanent hearing loss. There is no known cure, and the FDA has not approved any preventative treatment for cisplatin-based ototoxicity. OBJECTIVES: This study investigated whether the carbon monoxide (CO)-releasing tricarbonyldichlororuthenium (II) dimer, CORM-2, reverses cisplatin-induced hearing impairment and reduces cisplatin accumulation in the mouse inner ear. METHODS: Male 6-week-old BALB/c mice were randomly assigned to one of the following groups: control (saline-treated, i.p.), CORM-2 only (30 mg/kg, i.p., four doses), cisplatin only (20 mg/kg, i.p., one dose), and CORM-2 + cisplatin, to determine whether cisplatin-based hearing impairment was alleviated by CORM-2 treatment. RESULTS: Our results revealed CORM-2 significantly attenuated cisplatin-induced hearing loss in young adult mice. CORM-2 co-treatment significantly decreased platinum accumulation in the inner ear and activated the plasma membrane repair system of the stria vascularis. Moreover, CORM-2 co-treatment significantly decreased cisplatin-induced inflammation, apoptosis, and cochlear necroptosis. Because the stria vascularis is the likely cochlear entry point of cisplatin, we next focused on the microvasculature. Cisplatin induced increased extravasation of a chromatic tracer (fluorescein isothiocyanate [FITC]-dextran, MW 75 kDa) around the cochlear microvessels at 4 days post-treatment; this extravasation was completely inhibited by CORM-2 co-therapy. CORM-2 co-treatment effectively maintained the integrity of stria vascularis components including endothelial cells, pericytes, and perivascular-resident macrophage-type melanocytes. CONCLUSION: CORM-2 co-therapy substantially protects against cisplatin-induced ototoxicity by reducing platinum accumulation and toxic cellular stress responses. These data indicate that CORM-2 co-treatment may be translated into clinical strategy to reduce cisplatin-induced hearing loss.

2.
Biol Sex Differ ; 14(1): 10, 2023 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-36810096

RESUMO

BACKGROUND: Obesity is an independent risk factor for hearing loss. Although attention has focused on major obesity comorbidities such as cardiovascular disease, stroke, and type 2 diabetes, the impact of obesity on sensorineural organs, including the auditory system, is unclear. Using a high-fat diet (HFD)-induced obese mouse model, we investigated the impact of diet-induced obesity on sexual dimorphism in metabolic alterations and hearing sensitivity. METHODS: Male and female CBA/Ca mice were randomly assigned to three diet groups and fed, from weaning (at 28 days) to 14 weeks of age, a sucrose-matched control diet (10 kcal% fat content diet), or one of two HFDs (45 or 60 kcal% fat content diets). Auditory sensitivity was evaluated based on the auditory brainstem response (ABR), distortion product otoacoustic emission (DPOAE), and ABR wave 1 amplitude at 14 weeks of age, followed by biochemical analyses. RESULTS: We found significant sexual dimorphism in HFD-induced metabolic alterations and obesity-related hearing loss. Male mice exhibited greater weight gain, hyperglycemia, increased ABR thresholds at low frequencies, elevated DPOAE, and lower ABR wave 1 amplitude compared to female mice. The hair cell (HC) ribbon synapse (CtBP2) puncta showed significant sex differences. The serum concentration of adiponectin, an otoprotective adipokine, was significantly higher in female than in male mice; cochlear adiponectin levels were elevated by HFD in female but not male mice. Adiponectin receptor 1 (AdipoR1) was widely expressed in the inner ear, and cochlear AdipoR1 protein levels were increased by HFD, in female but not male mice. Stress granules (G3BP1) were significantly induced by the HFD in both sexes; conversely, inflammatory (IL-1ß) responses were observed only in the male liver and cochlea, consistent with phenotype HFD-induced obesity. CONCLUSIONS: Female mice are more resistant to the negative effects of an HFD on body weight, metabolism, and hearing. Females showed increased peripheral and intra-cochlear adiponectin and AdipoR1 levels, and HC ribbon synapses. These changes may mediate resistance to HFD-induced hearing loss seen in female mice.


Assuntos
Diabetes Mellitus Tipo 2 , Perda Auditiva , Feminino , Animais , Camundongos , Masculino , Caracteres Sexuais , Adiponectina , DNA Helicases , Camundongos Endogâmicos CBA , Proteínas de Ligação a Poli-ADP-Ribose , RNA Helicases , Proteínas com Motivo de Reconhecimento de RNA , Perda Auditiva/etiologia , Dieta Hiperlipídica , Obesidade
3.
Int J Mol Sci ; 22(18)2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34576224

RESUMO

Delivery of substances into the inner ear via local routes is increasingly being used in clinical treatment. Studies have focused on methods to increase permeability through the round window membrane (RWM) and enhance drug diffusion into the inner ear. However, the clinical applications of those methods have been unclear and few studies have investigated the efficacy of methods in an inner ear injury model. Here, we employed the medium chain fatty acid caprate, a biologically safe, clinically applicable substance, to modulate tight junctions of the RWM. Intratympanic treatment of sodium caprate (SC) induced transient, but wider, gaps in intercellular spaces of the RWM epithelial layer and enhanced the perilymph and cochlear concentrations/uptake of dexamethasone. Importantly, dexamethasone co-administered with SC led to significantly more rapid recovery from noise-induced hearing loss at 4 and 8 kHz, compared with the dexamethasone-only group. Taken together, our data indicate that junctional modulation of the RWM by SC enhances dexamethasone uptake into the inner ear, thereby hastening the recovery of hearing sensitivity after noise trauma.


Assuntos
Dexametasona/farmacocinética , Orelha Interna/efeitos dos fármacos , Perda Auditiva Provocada por Ruído/tratamento farmacológico , Janela da Cóclea/efeitos dos fármacos , Animais , Cóclea/efeitos dos fármacos , Ácidos Decanoicos/farmacologia , Dexametasona/administração & dosagem , Difusão , Sistemas de Liberação de Medicamentos/métodos , Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Ácidos Graxos/química , Audição , Masculino , Microscopia Eletrônica de Transmissão , Perilinfa/efeitos dos fármacos , Permeabilidade , Ratos
4.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445504

RESUMO

Although previous studies continuously report an increased risk of hearing loss in diabetes patients, the impact of the disease on the inner ear remains unexplored. Herein, we examine the pathophysiology of diabetes-associated hearing impairment and cochlear synaptopathy in a mouse model of diabetes. Male B6.BKS(D)-Leprdb/J (db/db, diabetes) and heterozygote (db/+, control) mice were assigned into each experimental group (control vs. diabetes) based on the genotype and tested for hearing sensitivity every week from 6 weeks of age. Each cochlea was collected for histological and biological assays at 14 weeks of age. The diabetic mice exerted impaired hearing and a reduction in cochlear blood flow and C-terminal-binding protein 2 (CtBP2, a presynaptic ribbon marker) expression. Ultrastructural images revealed severely damaged mitochondria from diabetic cochlea accompanied by a reduction in Cytochrome c oxidase subunit 4 (COX4) and CR6-interacting factor 1 (CRIF1). The diabetic mice presented significantly decreased levels of platelet endothelial cell adhesion molecule (PECAM-1), B-cell lymphoma 2 (BCL-2), and procaspase-9, but not procaspase-8. Importantly, significant changes were not found in necroptotic programmed cell death markers (receptor-interacting serine/threonine-protein kinase 1, RIPK1; RIPK3; and mixed lineage kinase domain-like pseudokinase, MLKL) between the groups. Taken together, diabetic hearing loss is accompanied by synaptopathy, microangiopathy, damage to the mitochondrial structure/function, and activation of the intrinsic apoptosis pathway. Our results imply that mitochondrial dysfunction is deeply involved in diabetic hearing loss, and further suggests the potential benefits of therapeutic strategies targeting mitochondria.


Assuntos
Diabetes Mellitus Experimental/complicações , Perda Auditiva/fisiopatologia , Mitocôndrias/ultraestrutura , Receptores para Leptina/genética , Animais , Apoptose , Biomarcadores/metabolismo , Cóclea/irrigação sanguínea , Cóclea/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Modelos Animais de Doenças , Regulação para Baixo , Perda Auditiva/etiologia , Perda Auditiva/genética , Perda Auditiva/metabolismo , Humanos , Masculino , Camundongos , Microscopia Eletrônica de Transmissão , Mitocôndrias/metabolismo
5.
Int J Mol Sci ; 21(7)2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32260310

RESUMO

Age-related hearing loss (ARHL) is an irreversible, progressive neurodegenerative disorder and is presently untreatable. Previous studies using animal models have suggested mitochondrial damage and programmed cell death to be involved with ARHL. Thus, we further investigated the pathophysiologic role of mitochondria and necroptosis in aged C57BL/6J male mice. Aged mice (20 months old) exhibited a significant loss of hearing, number of hair cells, neuronal fibers, and synaptic ribbons compared to young mice. Ultrastructural analysis of aged cochleae revealed damaged mitochondria with absent or disorganized cristae. Aged mice also showed significant decrease in cochlear blood flow, and exhibited increase in gene expression of proinflammatory cytokines (IL-1ß, IL-6, and TNF-α), receptor-interacting serine/threonine-protein kinase 1 and 3 (RIPK1 and RIPK3) and the pseudokinase mixed-lineage kinase domain-like (MLKL). Immunofluorescence (IF) assays of cytochrome C oxidase I (COX1) confirmed mitochondrial dysfunction in aged cochleae, which correlated with the degree of mitochondrial morphological damage. IF assays also revealed localization and increased expression of RIPK3 in sensorineural tissues that underwent significant necroptosis (inner and outer hair cells and stria vascularis). Together, our data shows that the aging cochlea exhibits damaged mitochondria, enhanced synthesis of proinflammatory cytokines, and provides new evidence of necroptosis in the aging cochlea in in vivo.


Assuntos
Envelhecimento/fisiologia , Cóclea/ultraestrutura , Perda Auditiva Neurossensorial/patologia , Mitocôndrias/patologia , Animais , Cóclea/irrigação sanguínea , Cóclea/patologia , Citocinas/genética , Modelos Animais de Doenças , Potenciais Evocados Auditivos do Tronco Encefálico , Perda Auditiva Neurossensorial/genética , Masculino , Camundongos Endogâmicos C57BL , Mitocôndrias/ultraestrutura , Necroptose , Proteínas Quinases/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/genética
6.
Int J Mol Sci ; 20(21)2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31731459

RESUMO

Noise exposure affects the organ of Corti and the lateral wall of the cochlea, including the stria vascularis and spiral ligament. Although the inner ear vasculature and spiral ligament fibrocytes in the lateral wall consist of a significant proportion of cells in the cochlea, relatively little is known regarding their functional significance. In this study, 6-week-old male C57BL/6 mice were exposed to noise trauma to induce transient hearing threshold shift (TTS) or permanent hearing threshold shift (PTS). Compared to mice with TTS, mice with PTS exhibited lower cochlear blood flow and lower vessel diameter in the stria vascularis, accompanied by reduced expression levels of genes involved in vasodilation and increased expression levels of genes related to vasoconstriction. Ultrastructural analyses by transmission electron microscopy revealed that the stria vascularis and spiral ligament fibrocytes were more damaged by PTS than by TTS. Moreover, mice with PTS expressed significantly higher levels of proinflammatory cytokines in the cochlea (e.g., IL-1ß, IL-6, and TNF-α). Overall, our findings suggest that cochlear microcirculation and lateral wall pathologies are differentially modulated by the severity of acoustic trauma and are associated with changes in vasoactive factors and inflammatory responses in the cochlea.


Assuntos
Cóclea , Citocinas/metabolismo , Perda Auditiva Provocada por Ruído , Ferimentos e Lesões , Animais , Velocidade do Fluxo Sanguíneo , Cóclea/irrigação sanguínea , Cóclea/metabolismo , Cóclea/ultraestrutura , Modelos Animais de Doenças , Perda Auditiva Provocada por Ruído/metabolismo , Perda Auditiva Provocada por Ruído/patologia , Perda Auditiva Provocada por Ruído/fisiopatologia , Masculino , Camundongos , Ferimentos e Lesões/metabolismo , Ferimentos e Lesões/patologia , Ferimentos e Lesões/fisiopatologia
7.
Sci Rep ; 9(1): 12646, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477769

RESUMO

Glucocorticoid (GC) is a steroid hormone secreted from the adrenal cortex in response to stress, which acts by binding to cytoplasmic glucocorticoid receptors (GRs). Dexamethasone (DEX) is a synthetic GC exhibiting immunosuppressive effects in both human and rodent models of hearing loss. While clinical evidence has shown the effectiveness of DEX for treatment of various inner ear diseases, its mechanisms of action and the optimal timing of treatment are not well understood. In the present study, intergroup comparisons were conducted based on the time point of treatment with DEX: (1) pretreatment; (2) posttreatment; and (3) pre&post-noise. The pre&post DEX treatment group showed a significant improvement in threshold shift at 1 day post-noise exposure as compared to the TTS (transient threshold shift)-only group at 8 and 16 kHz. Both TTS and PTS (permanent threshold shift) significantly reduced cochlear GR mRNA expression and increased serum corticosterone and cochlear inflammatory cytokines. The pre&post DEX treatment group showed a significant decrease in serum corticosterone level as compared to other DEX treatment groups and TTS-treated group at 3 days after acoustic trauma. Our results suggest that the timing of DEX administration differentially modulates systemic steroid levels, GR expression and cochlear cytokine expression.


Assuntos
Cóclea/metabolismo , Corticosterona/sangue , Dexametasona/administração & dosagem , Perda Auditiva Provocada por Ruído/sangue , Perda Auditiva Provocada por Ruído/metabolismo , Receptores de Glucocorticoides/metabolismo , Animais , Limiar Auditivo , Sobrevivência Celular , Citocinas/sangue , Dexametasona/uso terapêutico , Modelos Animais de Doenças , Esquema de Medicação , Epitélio/patologia , Potenciais Evocados Auditivos do Tronco Encefálico , Células Ciliadas Auditivas/patologia , Perda Auditiva Provocada por Ruído/tratamento farmacológico , Perda Auditiva Provocada por Ruído/fisiopatologia , Mediadores da Inflamação/sangue , Masculino , Camundongos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Glucocorticoides/genética
8.
Biomed Res Int ; 2018: 7601232, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29619376

RESUMO

Diabetes can lead to many end-organ complications. However, the association between diabetes and hearing loss is not well understood. Here, we investigated the effect of noise exposure on diabetic mice compared with wild-type mice. Hearing threshold shifts, histopathologic changes in the cochlea, and inflammatory responses were evaluated over time. After noise exposure, more severe hearing threshold shifts, auditory hair cell loss, and synaptopathies were notable in diabetic mice compared with wild-type mice. Moreover, increased inflammatory responses and reactive oxygen species production were observed in the ears of diabetic mice. The results demonstrated that diabetic mice are more susceptible to noise trauma.


Assuntos
Diabetes Mellitus Experimental/complicações , Ruído/efeitos adversos , Ferimentos e Lesões/complicações , Animais , Limiar Auditivo , Contagem de Células , Sobrevivência Celular , Citocinas/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Suscetibilidade a Doenças , Epitélio/patologia , Epitélio/fisiopatologia , Potenciais Evocados Auditivos do Tronco Encefálico , Células Ciliadas Auditivas Externas/patologia , Mediadores da Inflamação/metabolismo , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Sinapses/patologia , Ferimentos e Lesões/fisiopatologia
9.
PLoS One ; 13(3): e0195230, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29601595

RESUMO

Preservation of residual hearing after cochlear implant is an important issue with regards to hearing performance. Various methods of steroid administration have been widely used in clinical practice to reduce inflammation and preserve residual hearing. Here we compare the effect of different routes of dexamethasone administration on intracochlear inflammation and residual hearing in guinea pig ears. Dexamethasone was delivered into the guinea pigs either through intracochlear, intratympanic or systemic route. The intracochlear concentration of dexamethasone, residual hearing, inflammatory cytokines and histopathologic changes were evaluated over time. A higher intracochlear dexamethasone concentration was observed after intracochlear administration than through the other routes. Residual hearing was better preserved with local dexamethasone administration as was supported by the reduced inflammatory cytokines, more hair cell survival and less severe intracochlear fibrosis and ossification concurrently seen in the local delivery group than in the systemic group. The results demonstrate that local dexamethasone delivery can reduce intracochlear inflammation and preserve residual hearing better than in systemically administered dexamethasone.


Assuntos
Cóclea/efeitos dos fármacos , Cóclea/cirurgia , Dexametasona/administração & dosagem , Dexametasona/farmacologia , Audição/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Cóclea/patologia , Cóclea/fisiologia , Implante Coclear , Citocinas/metabolismo , Dexametasona/uso terapêutico , Vias de Administração de Medicamentos , Cobaias , Células Ciliadas Auditivas/efeitos dos fármacos , Células Ciliadas Auditivas/patologia , Inflamação/tratamento farmacológico , Inflamação/etiologia , Masculino
10.
Acta Otolaryngol ; 138(2): 128-134, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28990828

RESUMO

OBJECTIVES: The aim of this study was to determine the optimal diagnostic workup modalities for vascular pulsatile tinnitus through analysis of clinical and radiologic findings. MATERIALS AND METHODS: A total of 49 patients diagnosed with vascular pulsatile tinnitus along with their medical records and radiologic findings were thoroughly reviewed. RESULTS: Of these patients, 84% had venous lesions. The jugular bulb variants (67%) were the most common venous lesions followed by sigmoid sinus variants (12%). About 88% (43/49) of these lesions were detected with computed tomography of the temporal bone (TBCT) alone and the lesions were either venous or intratemporal artery in origin. Simple manual neck compression test was 93% sensitive in predicting venous lesions. A high suspicion for venous lesion coupled with manual neck compression test and selection of the optimal imaging technique are useful for the proper evaluation of vascular pulsatile tinnitus at the initial visit. CONCLUSION: Our stepwise strategy may increase the cost-effectiveness of the chosen imaging workup by reducing redundancy of multiple and simultaneous radiologic tests in patients with vascular pulsatile tinnitus.


Assuntos
Osso Temporal/diagnóstico por imagem , Zumbido/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Idoso , Fístula Arteriovenosa/complicações , Fístula Arteriovenosa/diagnóstico por imagem , Artérias Carótidas/diagnóstico por imagem , Pré-Escolar , Análise Custo-Benefício , Feminino , Humanos , Veias Jugulares/diagnóstico por imagem , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Zumbido/etiologia , Tomografia Computadorizada por Raios X/economia , Adulto Jovem
11.
J Audiol Otol ; 21(3): 152-155, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28942633

RESUMO

Cochlear implant (CI) surgery in cholesteatoma is challenging because of the risk of residual or recurrent infection. Although CI could be done with subtotal petrosectomy in single or staged surgery, this surgery needed additional surgical procedures to obliterate the mastoid cavity. This paper describes a new surgical technique for CI surgery in cholesteatoma without external auditory canal closure.

12.
Laryngoscope ; 126(11): E379-E385, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27328420

RESUMO

OBJECTIVES/HYPOTHESIS: The purpose of this study was to investigate the effect of early postnatal neurotrophin-3 (NT3) support on hearing acquisition. STUDY DESIGN: A prospective experimental animal study. METHODS: Adenoviral (Ad) vectors expressing green fluorescence protein (GFP) alone or in combination with NT3 were injected into the scala tympani through the round window of 5-postnatal-day-old (P5) rats. Changes in NT3 mRNA level, hearing thresholds, and morphological studies were done after the viral vector injection. RESULTS: NT3 mRNA was significantly increased in the Ad-GFP-NT3 group compared to the normal-developmental group and Ad-GFP alone group. GFP was widely expressed in the cochlea such as in the hair cells, supporting cell area, and spiral ganglion neurons. Auditory brainstem response thresholds were significantly lower in the Ad-GFP-NT3 group compared to the normal-developmental group and Ad-GFP alone group at P15. CONCLUSIONS: These results show that early postnatal NT3 overexpression may accelerate the acquisition of hearing in rats. LEVEL OF EVIDENCE: NA Laryngoscope, 126:E379-E385, 2016.


Assuntos
Vetores Genéticos/administração & dosagem , Proteínas de Fluorescência Verde/administração & dosagem , Audição/genética , Neurotrofina 3/genética , RNA Mensageiro/metabolismo , Animais , Cóclea/crescimento & desenvolvimento , Potenciais Evocados Auditivos do Tronco Encefálico/genética , Técnicas de Transferência de Genes , Terapia Genética/métodos , Estudos Prospectivos , Ratos , Ratos Sprague-Dawley , Janela da Cóclea , Rampa do Tímpano
13.
Acta Otolaryngol ; 136(7): 682-6, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27007704

RESUMO

CONCLUSION: Pneumolabyrinth is a very rare condition, even in otic capsule disrupting (OCD) fracture. Hearing was not always impaired, even in cases with OCD fracture. The co-existence of pneumocochlea, regarded as a risk factor for total hearing loss, was extremely rare in cases of pneumolabyrinth. OBJECTIVES: The purposes of this study were to analyze the radiological and clinical features in patients with pneumolabyrinth and to overcome the diagnostic pitfalls encountered during pneumocochlea detection. MATERIALS AND METHODS: The temporal bone computed tomographies (TBCT) of 402 patients diagnosed with temporal bone fracture along with their clinical records were retrospectively reviewed. RESULTS: Only six patients (7% of those with OCD fractures or 1.5% of those with temporal bone fracture) were found to have pneumolabyrinth. Locations of the pneumolabyrinth were in the vestibule in all six cases and three of them showed air densities both in the cochlea and semicircular canal. The size of the air density in the vestibule was 5.38 ± 4.56 mm(2) at the axial view and 6.57 ± 5.67 mm(2) at the coronal view. The mean minimal Hounsfield unit (HU) of air density area in the vestibule was -968.1 ± 22.94 at the axial view and -941 ± 16.88 at the coronal view. Patients with pneumocochlea eventually developed total hearing loss.


Assuntos
Traumatismos Craniocerebrais/diagnóstico , Enfisema/diagnóstico por imagem , Doenças do Labirinto/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
14.
Neural Plast ; 2016: 7287180, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26881130

RESUMO

Dizziness and vertigo frequently occur after cochlear implantation (CI) surgery, particularly during the early stages. It could recover over time but some of the patients suffered from delayed or sustained vestibular symptoms after CI. This study used rat animal models to investigate the effect of unilateral cochleostomy on the vestibular organs over time. Twenty-seven Sprague Dawley rats underwent cochleostomy to evaluate the postoperative changes in hearing threshold, gain and symmetry of the vestibular ocular response, overall balance function, number of hair cells in the crista, and the c-Fos activity in the brainstem vestibular nucleus. Loss of vestibular function was observed during the early stages, but function recovered partially over time. Histopathological findings demonstrated a mild decrease in vestibular hair cells numbers. Increased c-Fos immunoreactivity in the vestibular nucleus, observed in the early stages after cochleostomy, decreased over time. Cochleostomy is a risk factor for peripheral vestibular organ damage that can cause functional impairment in the peripheral vestibular organs. Altered vestibular nucleus activity may be associated with vestibular compensation and plasticity after unilateral cochleostomy.


Assuntos
Cóclea/cirurgia , Plasticidade Neuronal , Núcleos Vestibulares/fisiopatologia , Estimulação Acústica , Animais , Limiar Auditivo/fisiologia , Potenciais Evocados Auditivos do Tronco Encefálico , Células Ciliadas Vestibulares/patologia , Masculino , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Sprague-Dawley , Teste de Desempenho do Rota-Rod , Núcleos Vestibulares/metabolismo
15.
PLoS One ; 10(8): e0136617, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26308864

RESUMO

The aim of this study was to investigate the effects of intracochlear bleeding during cochleostomy on cochlear inflammatory response and residual hearing in a guinea pig animal model. Auditory brainstem response threshold shifts were greater in blood injected ears (p<0.05). Interleukin-1ß, interleukin-10, tumor necrosis factor-α and nitric oxide synthase 2, cytokines that are related to early stage inflammation, were significantly increased in blood injected ears compared to normal and cochleostomy only ears at 1 day after surgery; with the increased IL-1ß being sustained until 3 days after the surgery (p<0.05). Hair cells were more severely damaged in blood injected ears than in cochleostomy only ears. Histopathologic examination revealed more extensive fibrosis and ossification in blood injected ears than cochleostomy only ears. These results show that intracochlear bleeding enhanced cochlear inflammation resulting in increased fibrosis and ossification in an experimental animal model.


Assuntos
Cóclea/cirurgia , Implante Coclear/efeitos adversos , Fibrose/patologia , Transtornos da Audição/patologia , Hemorragia/complicações , Ossificação Heterotópica/patologia , Complicações Pós-Operatórias , Animais , Limiar Auditivo , Citocinas/metabolismo , Modelos Animais de Doenças , Potenciais Evocados Auditivos do Tronco Encefálico , Fibrose/etiologia , Fibrose/metabolismo , Cobaias , Células Ciliadas Auditivas/patologia , Transtornos da Audição/etiologia , Transtornos da Audição/metabolismo , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Masculino , Ossificação Heterotópica/etiologia , Ossificação Heterotópica/metabolismo
16.
Cell Res ; 21(6): 944-56, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21321603

RESUMO

We herein investigated the role of the STAT signaling cascade in the production of pro-inflammatory cytokines and cisplatin ototoxicity. A significant hearing impairment caused by cisplatin injection was observed in Balb/c (wild type, WT) and STAT4(-/-), but not in STAT6(-/-) mice. Moreover, the expression levels of the protein and mRNA of pro-inflammatory cytokines, including TNF-α, IL-1ß, and IL-6, were markedly increased in the serum and cochlea of WT and STAT4(-/-), but not STAT6(-/-) mice. Organotypic culture revealed that the shape of stereocilia bundles and arrays of sensory hair cell layers in the organ of Corti from STAT6(-/-) mice were intact after treatment with cisplatin, whereas those from WT and STAT4(-/-) mice were highly distorted and disarrayed after the treatment. Cisplatin induced the phosphorylation of STAT6 in HEI-OC1 auditory cells, and the knockdown of STAT6 by STAT6-specific siRNA significantly protected HEI-OC1 auditory cells from cisplatin-induced cell death and inhibited pro-inflammatory cytokine production. We further demonstrated that IL-4 and IL-13 induced by cisplatin modulated the phosphorylation of STAT6 by binding with IL-4 receptor alpha and IL-13Rα1. These findings suggest that STAT6 signaling plays a pivotal role in cisplatin-mediated pro-inflammatory cytokine production and ototoxicity.


Assuntos
Antineoplásicos/toxicidade , Cisplatino/toxicidade , Citocinas/metabolismo , Citotoxinas/toxicidade , Fator de Transcrição STAT6/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cóclea/efeitos dos fármacos , Cóclea/patologia , Citocinas/genética , Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Genes Reporter , Células Ciliadas Auditivas/efeitos dos fármacos , Células Ciliadas Auditivas/patologia , Perda Auditiva/induzido quimicamente , Perda Auditiva/patologia , Perda Auditiva/fisiopatologia , Luciferases/biossíntese , Luciferases/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , NF-kappa B/genética , NF-kappa B/metabolismo , Fosforilação , Regiões Promotoras Genéticas , Interferência de RNA , Fator de Transcrição STAT4/genética , Fator de Transcrição STAT4/metabolismo , Fator de Transcrição STAT6/genética , Transcrição Gênica
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA