Effect of Inner Hair Cell Loss and Afferent Damage on Functional Hearing

内毛细胞损失和传入损伤对功能性听力的影响

基本信息

批准号：
10049236
负责人：
Edward Lobarinas
金额：
$ 31.57万
依托单位：
UNIVERSITY OF TEXAS DALLAS
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-12-07 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10049236
关键词：
Acoustic Nerve Action Potentials Acute Animal Experiments Animal Model Animals Applications Grants Auditory Auditory Brainstem Responses Auditory Evoked Potentials Auditory Threshold Behavioral Bilateral Carboplatin Chinchilla (genus)Chronic Cochlea Data Diagnosis Discrimination Dose Early Diagnosis Early Intervention Evoked Potentials Exposure to Frequencies Goals Growth Health Hearing Hearing Tests Human Hyperacusis Individual Inner Hair Cells Label Labyrinth Lesion Loudness Masks Measures Monitor Nerve Fibers Noise Noise-Induced Hearing Loss Occupational Noise Output Pathology Pattern Phase Physiological Presbycusis Rehabilitation therapy Risk Factors Site Speech Synapses Testing Tinnitus Work behavior measurement density early onset hazard hearing impairment hidden hearing loss interest ototoxicity programs relating to nervous system response speech in noise

项目摘要

ABSTRACT Audiometry, or threshold testing at frequencies essential for speech understanding, is the most common and universally accepted metric for hearing health. However, it is becoming clear from animal studies that there can be significant inner ear damage that is undetected by threshold measures and among hearing impaired individuals there can be substantial variability in functional metrics of hearing such as hearing in noise even across individuals with similar thresholds and no evidence of retrocochlear pathology. These findings have generated tremendous interest in “hidden hearing loss” characterized by inner ear damage that is undetected by threshold measures. There is now speculation that loss of afferent synapses may underlie hearing-in-noise deficits, hyperacusis, and tinnitus. However, what is the evidence for functional deficits and where do these deficits begin? Surprisingly, there is no current evidence of any significant functional deficits associated with synaptopathy in animals and there is no compelling evidence in humans. Thus, it is essential to determine the critical boundaries for when functional deficits associated with hidden hearing loss begin. Establishing the relationship between specific patterns of cochlear damage such as loss of inner hair cells (IHC) or synapses and the corresponding functional deficits undetected by thresholds are critical in understanding risk factors, early detection, and intervention for early onset or undetected hearing loss. The overall aims of this proposal is to evaluate functional hearing impairment in an animal model with degradation of afferent synapses using noise-exposure or selective ototoxic loss of inner hair cells in the absence of corresponding threshold elevations. Specifically, what is the effect of this “hidden” but significant cochlear pathology on hearing-in-noise, intensity discrimination, forward masking, tinnitus and physiological correlates of functional hearing? When do these deficits begin? When completed, this work will explicitly define the functional deficits encompassed within “hidden hearing losses” induced by noise exposure or carboplatin. These data will provide the evidence urgently needed to guide potential changes to auditory monitoring plans recommended as best practice in hearing conservation programs, enhance site of lesion diagnosis, and reveal hidden functional deficit targets for rehabilitative purposes.

抽象的听力测定法或以语音理解必不可少的频率测试是最常见的，并且公认的听力健康指标。但是，从动物研究中可以清楚地知道要受到阈值措施和听力障碍的明显内耳损伤在听力的功能指标上，诸如噪声中听力的功能指标也可能存在很大的差异跨阈值相似且没有证据表明右病理学的个体。这些发现有对以内耳损害为特征的“隐藏听力损失”产生了极大的兴趣通过阈值措施。现在有猜测，传入突触的损失可能是毫无言论的基础缺陷，超源和耳鸣。但是，功能性缺陷的证据是什么？缺陷开始了吗？令人惊讶的是，目前没有证据表明与动物的突触病，人类没有令人信服的证据。那是必须确定何时与隐藏听力损失开始的功能缺陷时的关键边界。建立人工耳蜗损害的特定模式之间的关系，例如内毛细胞（IHC）或突触之间的关系阈值未发现的相应功能缺陷对于理解风险因素，至关重要早期检测和干预早期发作或未检测到的听力损失。该提案的总体目的是评估动物模型中的功能听力障碍使用噪声暴露或选择性耳毒性损失内毛细胞中的传入突触降解没有相应的阈值抬高。特别是，这种“隐藏”但重要的影响是什么关于听力中的耳蜗病理学，强度歧视，前掩蔽，耳鸣和生理学功能听力的关联？这些定义什么时候开始？完成后，这项工作将明确定义噪声暴露或卡铂引起的“隐藏听力损失”中的功能缺陷。这些数据将提供迫切需要的证据，以指导潜在的听觉监控计划更改建议作为听力保护计划的最佳实践，增强病变诊断现场并揭示隐藏的功能不足目标用于康复目的。