Otitis Media Impact on the Inner Ear

中耳炎对内耳的影响

基本信息

批准号：
7244265
负责人：
DENNIS ROYAL TRUNE
金额：
$ 18.69万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-07-01 至 2009-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7244265
关键词：
Accounting Acute Adult Age Age of Onset Amino Acid Substitution Animal Model Animals Antibiotic Therapy Antibiotics Apoptosis Audiometry Auditory Brainstem Responses B Cell Proliferation Bacteria Bacterial DNA Bacterial Infections Binding Blood Blood - brain barrier anatomy Blood Vessels Bone Conduction C3H/HeJ Mouse CCL2 gene Case Study Cell Surface Receptors Cell Wall Cells Characteristics Child Childhood Cholesteatoma Chronic Chronic Disease Clinical Clinical Research Collaborations Conductive hearing loss Connective Tissue Cross-Sectional Studies Cytokine Gene DNA Defect Deposition Detection Development Dexamethasone Diagnosis Disease Drainage procedure Ear Edema Electron Microscopy Elevation Endothelial Cells Endotoxins Enzyme-Linked Immunosorbent Assay Enzymes Epidermal Growth Factor Epithelial Epithelial Cells Epithelium Eustachian Tube Experimental Animal Model Extravasation Fibroblasts Fibrosis Frequencies Gene Expression Genetic Genetic Polymorphism Genetic Transcription Gentamicins Glycoproteins Goals Gram-Negative Bacteria Granulation Tissue Growth Factor Haemophilus influenzae Hair Cells Hearing Heating Hour Human Hyperplasia Hypertrophy Immune Immune response Immune system Immunoglobulin G Immunohistochemistry Immunologics Immunology Inbred BALB C Mice Inbred C3H Mice Incidence Individual Infection Infectious Agent Infiltration Inflammation Inflammatory Inflammatory Response Influenza Injection of therapeutic agent Intercellular adhesion molecule 1 Interferons Interleukin-10 Interleukin-12 Interleukin-2 Interleukin-2/Interleukin-6 Interleukin-8 Interleukins Invaded Investigation Labyrinth Language Development Lateral Lead Ligaments Ligation Light Lipopolysaccharides Liquid substance Macrophage Inflammatory Proteins Measurement Measures Mediating Mediator of activation protein Medical Membrane Meningitis Methods Microspheres Modeling Molecular Moraxella Movement Mucins Mucous body substance Mus NF-kappa B Nature Nitric Oxide Nitric Oxide Synthase Nuclear Nucleic Acids Numbers Obstruction Office Visits Operative Surgical Procedures Osteoclasts Otitis Media Otitis Media with Effusion Parents Pathology Patients Pattern Peptides Peptidoglycan Permeability Physiology Platelet Activating Factor Play Pneumonia Polyamines Population Predisposition Prevalence Prevalence Study Prevention Principal Investigator Procedures Process Production Property Publications Reaction Reactive Oxygen Species Recording of previous events Recurrence Reporting Research Research Personnel Resistance Risk Risk Factors Route Sample Size Sensorineural Hearing Loss Serous Serum Severities Shock Siblings Side Small Inducible Cytokine A3 Speech Staging Streptococcus pneumoniae Stria Vascularis Suggestion Sweden Symptoms T-Lymphocyte TLR2 gene Temporal bone structure Testing Thick Tight Junctions Time Tissues Toll-like receptors Toxin Transcription factor genes Tube Tumor Necrosis Factor-alpha Tumor Necrosis Factors Vascular Endothelial Cell Vascular Endothelial Growth Factor Receptor Vascular Endothelial Growth Factors Vascular Permeabilities Week bacterial resistance base bone cell type cost cytokine day ear infection effusion extracellular hearing impairment human GJB2 protein human TLR4 protein human TNF protein inner ear diseases interest killings lipoteichoic acid macrophage method development middle ear middle ear disorder monocyte mouse model neovascularization neutrophil pathogen prevent programs protein expression receptor response round window sound species difference symposium toll-like receptor 4 transcription factor

项目摘要

DESCRIPTION (provided by applicant): In spite of decades of study, it is still not clear how otitis media impacts the inner ear to cause sensorineural hearing loss. Thus, it is impossible to predict who is at risk or what markers can be used to determine if inner ear inflammation is occurring, making effective diagnosis and management difficult. Therefore, our bng-term goal is to identify how inflammation in the middle ear causes cochlear pathology. The PI and his colleagues, has recently developed an acute otitis media mouse model, as well as described chronic otitis media in the C3H/HeJ mouse that has a defect in its toll like receptor 4 (TLR4). These collaborations have led to the development of new methods to characterize both middle ear and inner ear cytokine expression, nuclear factor-kB (NF-kB)-mediated inflammatory processes, nitric oxide-mediated cochlear damage, and quantitative immune cell pathology. The proposed studies will capitalize on both these acute and chronic middle ear disease mouse models to establish the correlative middle ear and inner ear immune profiles. This will describe for the first time the molecular immune mechanisms by which otitis media can directly cause inner ear pathology. Therefore, this research has the potential to significantly advance our understanding of inner ear inflammatory processes elicited by both acute and chronic otitis media and lay the groundwork for development of new procedures for the detection and therapy of sensorineural hearing loss. The proposed studies will utilize BALB/c mice inoculated in the middle ear with heat-killed Haemophilous influenza or Streptococcus pneumoniae (acute otitis media) and C3H/HeJ mice defective for TLR4 (chronic otitis media) to characterize inner ear pathology, physiology, cytokine gene expression, cytokine levels, NF- kB activated inflammatory processes, and reactive oxygen species. The specific aims of this proposal are: Aim 1: To characterize the inner ear inflammatory profile in acute otitis media. This will test the hypothesis that acute otitis media causes a transient inner ear immune response characterized by Thl inflammatory processes. Aim 2: To characterize the inner ear inflammatory profile in chronic otitis media. This will test the hypothesis that chronic otitis media causes a persistent and destructive inner ear immune response characterized by expanded Th1 inflammatory processes. Inner ear pathology will be measured with auditory brainstem response audiometry, the endocochlear potential, light and electron microscopy, and immunohistochemistry of inflammatory mediators. Cochlear immune-mediated processes will be assessed by measurement of inflammatory cytokines, cytokine gene expression, and ELISA of transcription factors, vascular related factors, and reactive oxygen species.

描述（由申请人提供）：尽管进行了数十年的研究，但仍不清楚中耳炎如何影响内耳以引起感官性听力损失。因此，不可能预测谁处于危险之中或可以使用哪些标记来确定是否正在发生内耳炎症，从而使有效的诊断和管理变得困难。因此，我们的BNG期限目标是确定中耳炎症如何引起人工耳蜗病理。 PI和他的同事最近开发了一种急性中耳球培养基小鼠模型，并描述了C3H/HEJ小鼠中的慢性中耳炎培养基，该模型在其TOLL中具有缺陷，例如受体4（TLR4）。这些合作导致了新方法的发展，以表征中耳和内耳细胞因子表达，核因子-KB（NF-KB）介导的炎症过程，一氧化氮介导的耳蜗损伤和定量免疫细胞病理学。拟议的研究将利用这些急性和慢性中耳病小鼠模型，以建立相关性中耳和内耳的免疫特征。这将首次描述中耳炎可以直接引起内耳病理学的分子免疫机制。因此，这项研究有可能显着提高我们对急性和慢性中耳炎引起的内耳炎症过程的理解，并为开发新程序开发检测和治疗感觉性听力损失的基础。 The proposed studies will utilize BALB/c mice inoculated in the middle ear with heat-killed Haemophilous influenza or Streptococcus pneumoniae (acute otitis media) and C3H/HeJ mice defective for TLR4 (chronic otitis media) to characterize inner ear pathology, physiology, cytokine gene expression, cytokine levels, NF- kB activated inflammatory过程和活性氧。该提案的具体目的是：目标1：表征急性中耳性中耳炎症培养基中的内耳炎症特征。这将检验以下假设：急性中耳炎会导致以THL炎症过程为特征的短暂性内耳免疫反应。目的2：表征慢性中耳性中耳炎症性特征。这将检验以下假设：慢性中耳炎培养基会导致持续性和破坏性的内耳免疫反应，其特征是扩大Th1炎症过程。内耳病理学将通过听觉的脑干反应测量法，内核势，光和电子显微镜以及炎症介质的免疫组织化学来测量。耳蜗免疫介导的过程将通过测量炎症细胞因子，细胞因子基因表达和转录因子的ELISA，血管相关因子和活性氧物种来评估。