Intense Noise Exposure Impacts Performance of Vestibular Dependent Behaviors

摘要 军事人员在他们的现役职业生涯中暴露于武器，爆炸和噪音的强烈噪音中。 军用车辆，如坦克、直升机和其他飞机。暴露在强烈的噪音中会导致听力损失 并且还可能引起前庭功能障碍。虽然听力损失和耳蜗突触病已经得到了很好的研究， 外周前庭突触病和前庭功能障碍很少被研究并且特征不明显。 此外，与年龄相关的平衡赤字是美国退伍军人的一个重大公共卫生问题。 Agrawal等报道，35%的40岁以上的成年人有姿势不稳定和平衡的证据 功能障碍随着年龄的增长而增加，因此到80岁时，85%的成年人报告有平衡问题。前庭 功能障碍可增加跌倒的可能性;在美国，福尔斯是导致 生活质量，以及超过50%的意外死亡。尽管姿势不稳定的原因很复杂 和多因素，一些研究表明，噪音引起的听力损失和前庭 人类的功能障碍噪声暴露作为前庭功能丧失的危险因素， 健康的影响，但很少有研究，如果有的话，（1）提供深入了解生理基础， 噪声引起的前庭功能丧失;（2）为退伍军人的预防或康复策略提供指导 平衡失调拟议中的研究将表明，在大鼠模型中， 退伍军人在服兵役期间和日常生活中可能会导致前庭功能障碍，包括 前庭反射和前庭信号缺陷，增加跌倒风险并降低头部稳定性和视觉 运动时的敏锐度。 我们假设强噪声暴露足以减弱前庭神经对线性刺激的反应， 加速（如通过前庭短潜伏期诱发电位（VsEP）评估的）也将引起显著的 三种前庭依赖行为的功能缺陷，（1）运动过程中的平衡控制;（2）缺陷 降低头部稳定性前庭反射功能;（3）前庭-眼反射功能缺陷 足以降低运动期间的视觉灵敏度。 具体目标1。评估暴露于强噪声的大鼠的平衡，头部和视觉稳定性，足以消除 VsEP反应至少28天。我们将利用这一时间窗口来探讨时间进程和性质， 噪声暴露导致的前庭依赖行为缺陷。具体目标2A.确定是否 不是同样的行为受到单一噪声暴露的损害，导致暂时的损失和恢复。 28天内的VsEP反应。该目标将确定是否有一个功能性前庭的影响，从一个单一的 噪声暴露后，外周突触和VsEP反应恢复。具体目标2B。确定 这些行为的程度和时间进程受到多种噪声暴露的损害， 最初诱导VsEP反应暂时衰减。该目标将确定累积前庭 重复噪声暴露的影响（退伍军人在服役期间通常会经历） 潜在的外围和中央恢复机制，可以有针对性的康复策略。

Abstract Military personnel are exposed to intense noise during their active duty careers from weaponry, explosions and military vehicles such as tanks, helicopters and other aircraft. Exposure to intense noise causes hearing loss and may also cause vestibular dysfunction. Although hearing loss and cochlear synaptopathy are well studied, peripheral vestibular synaptopathy and vestibular dysfunction are less often studied and poorly characterized. Furthermore, age related balance deficits are a significant public health problem for veterans in the United States. Agrawal et al. reported that 35% of adults older than 40 had evidence of postural instability and balance dysfunction increased with age so that by 80 years, 85% of adults reported balance problems. Vestibular dysfunction can increase the likelihood of falling; in the US falls are responsible for significant decrements in quality of life, and more than 50% of accidental deaths. Although the causes of postural instability are complex and multifactorial, several studies demonstrate a linkage between noise induced hearing loss and vestibular dysfunction in humans. Noise exposure as a risk factor for vestibular loss has obvious and significant veteran health implications, but there are few, if any studies that (1) provide insights into the physiology that underlies noise-induced vestibular loss and (2) provide guidance for preventative or rehabilitative strategies for veterans with balance disorders. The proposed studies will show in a rat model, that noise exposure at levels encountered by veterans during their military service and during daily life can cause vestibular dysfunction that includes deficits in vestibular reflexes and vestibular signaling that increase fall risk and reduce head stability and visual acuity during movement. We hypothesize that intense noise exposure sufficient to attenuate vestibular nerve responses to linear acceleration (as assessed by the Vestibular short latency Evoked Potential (VsEP) will also cause significant functional deficits in three vestibular dependent behaviors, (1) control of balance during locomotion; (2) deficits in vestibulocollic reflex function that reduce head stability; and (3) deficits in vestibulo-ocular reflex function sufficient to reduce visual acuity during locomotion. Specific Aim 1. Assess balance, head, and visual stability in rats exposed to intense noise sufficient to abolish VsEP responses for at least 28 days. We will use this time window to probe the time course and nature of deficits in vestibular dependent behaviors caused by noise exposure. Specific Aim 2A. Determine whether or not the same behaviors are impaired by a single noise exposure that induces temporary loss and recovery of VsEP responses within 28 days. This Aim will determine if there is a functional vestibular impact from a single noise exposure after which peripheral synapses and VsEP responses recover. Specific Aim 2B. Determine the extent to which and the time course over these behaviors are impaired by multiple noise exposures that initially induce temporary attenuations of VsEP responses. This Aim will determine the cumulative vestibular impact of repetitive noise exposures (as would typically be experienced by Veterans during their service years) on potential peripheral and central recovery mechanisms that can be targeted by rehabilitative strategies.