The Effect of Noise Exposure on the Vestibular System

噪音暴露对前庭系统的影响

• 批准号: 9079646
• 负责人: Faith Wurm Akin
• 金额: --
• 依托单位: JAMES H QUILLEN VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9079646
• 关键词: 3-nitrotyrosine; 4 hydroxynonenal; Address; Animal Model; Animals; Antibodies; Area; Auditory; Cells; Cervical; Clinical; Clinical Protocols; Cochlea; Control Groups; Development; Diagnosis; Dizziness; Epithelium; Equilibrium; Evaluation; Exposure to; Fire - disasters; Free Radical Formation; Frequencies; Functional disorder; Goals; Head; Hearing; Human; Individual; Investigation; Knowledge; Magnetic Resonance Imaging; Manganese; Maps; Military Personnel; Mission; Modeling; Molecular; Neuraxis; Neurons; Noise; Noise-Induced Hearing Loss; Organ; Outer Hair Cells; Pathway interactions; Patient Care; Peripheral; Quality of life; Rattus; Saccule and Utricle; Safety; Semicircular canal structure; Sensory; Sensory Receptors; Services; Symptoms; System; Test Result; Testing; Therapeutic; Utricle structure; Vertigo; Vestibular Function Tests; Vestibular Hair Cells; Vestibular Nerve; Vestibular loss; Veterans; Work; arm; equilibration disorder; hearing impairment; imaging modality; improved; interest; novel; novel therapeutics; otoconia; prevent; public health relevance; rehabilitation strategy; vestibular pathway

 DESCRIPTION (provided by applicant): Observations in the military have shown that exposure to battlefield-related noise can cause balance disorders characterized by postural instability, dizziness, and vertigo; however, underlying mechanisms are not well understood. One reason for this knowledge gap may be that most previous assessments have been focused on evaluation of horizontal semicircular canal function. Recent animal and human studies, however, provide evidence that noise overstimulation impacts the "sacculus;" the vestibular end-organ closest to cochlea, to a much greater extent than any of the other vestibular sensory receptors (Akdogan et al., 2009; Akin et al., 2012). New developments in the use of cervical and ocular vestibular evoked myogenic potentials combined with video head impulse testing, now allow all five vestibular sensory organs (three semicircular canals and two otolith end organs - utricle and saccule) to be assessed in a comprehensive manner that allows the functional integrity of each to be differentiated. This novel test battery allows assessment in a rapid and non-invasive manner following noise exposure. The underlying hypothesis of the proposed studies is that a noise sufficient to induce hearing loss can also induce dysfunction in the sacculus, often without effects on other vestibular end-organs. This will be tested in Veterans with noise-induced hearing loss and in the rat, with the animal studies able to define and control the noise exposure conditions. The use of parallel human and animal studies provides the ability to correlate specific cellular damage (from animal studies) with the noise-induced dysfunction (found in both the human and animal investigations) as well as to identify underlying molecular mechanisms that could point to therapeutics for treatment. Manganese enhanced magnetic resonance imaging (MEMRI) is a powerful imaging modality used to map and assess whether a central nervous system pathway remains intact following insult and to determine changes in activity following peripheral damage (Pautler, 2004, 2006; Holt et al., 2010; Cacace et al., 2014). We hypothesize that sacculus evoked central vestibular activity will change following noise overstimulation. Specific Aim 1: Test the hypothesis that noise that causes permanent threshold shifts in hearing sensitivity will also cause vestibular dysfunction in the sacculus with less effet in the utricle and semicircular canals in humans and in animals. Specific Aim 2A: Test the hypothesis that noise that causes moderate loss of cochlear outer hair cells will also cause loss of vestibular hair cells and calyceal vestibular nerve connections and this loss will primarily be found in the sacculus with less effect in the utricle or semicircular canals. Aim 2B: Test the hypothesis that noise overstimulation that causes increased free radical formation in cochlear sensorineural epithelium will cause a similar increase in the sacculus. Specific Aim 3: Test the hypothesis that noise that causes moderate loss of cochlear outer hair cells will also cause changes in neuronal activity within the sacculus-associated central vestibular pathways.

 描述（由申请人提供）： 军方的观察表明，与战场相关的噪音接触会导致平衡疾病，其特征是姿势不稳定，头晕和眩晕。但是，基本机制尚不清楚。该知识差距的原因之一可能是，大多数以前的评估都集中在评估水平半圆形管功能上。然而，最近的动物和人类研究提供了证据，表明噪声过度刺激会影响“ sacculus”；前庭端管道最接近耳蜗，其程度要比其他前庭感觉受体大得多（Akdogan等，2009； Akin等，2012）。使用宫颈和眼前庭诱发的肌源潜力以及视频头脉冲测试的新发展，现在允许所有五个前庭感觉器官（三个半圆形管和两个耳鼻喉科器官 - 乌特利斯和囊泡）以全面的方式进行评估，以允许每种完整性的整体性。这种新颖的测试电池可在噪声暴露后以快速和非侵入性的方式进行评估。拟议的研究的基本假设是，足以引起听力损失的噪声也会诱导囊中的功能障碍，通常对其他前庭端孔没有影响。这将在具有噪声引起的听力损失和大鼠的退伍军人中进行测试，动物研究能够定义和控制噪声暴露条件。平行人类和动物研究的使用提供了将特定的细胞损伤（来自动物研究）与噪声诱导的功能障碍（在人类和动物研究中发现）以及鉴定可能指向治疗治疗治疗的基本分子机制的能力。锰增强的磁共振成像（MEMRI）是一种强大的成像方式，用于绘制和评估损伤后中枢神经系统途径是否保持完整并确定外周损伤后活动变化（Pautler，2004，2006; Holt等，2010; Cacace等，2014）。我们假设在噪声过度刺激之后，sacculus引起的中央前庭活动会改变。具体目的1：检验以下假设：导致听力敏感性的永久阈值转移的噪声也会导致囊中前庭功能障碍，在乌特莱斯和动物中的尿中和半圆形管中的影响较小。特定目标2a：检验以下假设：导致耳蜗外毛细胞中等损失的噪声也会导致前庭毛细胞和钙孔的前庭神经连接的丧失，并且这种损失将在囊中发现，在胸花或半管道中影响较小。 AIM 2B：测试以下假设：导致耳蜗外毛细胞中等损失的噪声也会导致前庭毛细胞和钙孔的前庭神经连接的丧失，并且这种损失将主要在囊中发现，在肠子或半管道中影响较小。过度刺激会导致人工耳蜗感官上皮的自由基形成增加，这会导致囊量相似。特定目标3：检验以下假设：导致耳蜗外毛细胞中等损失的噪声也会导致囊中的中央前庭途径内神经元活性的变化。