Evaluation of a structure-function model for auditory consequences of impact acceleration brain injury and protection via the olivocochlear system

项目摘要 听觉功能障碍可以在脑损伤后急剧发生，并在损伤后随着时间的推移而继续变化。脑区 即使在进行损伤时，损伤也会导致结构和功能后果的异质性 在受控实验室环境中也是如此。脑损伤对听觉系统功能的影响尚未见报道 在动物模型中进行了系统的纵向检查，以了解导致 异质性。这项建议的目标是调查听力功能结果的异质性 冲击加速TBI(IA-TBI)或假条件，并寻找潜在结构与损伤的相关性 耳朵和脑干。在目标1中，我们将评估听觉功能和相应的神经退行性变模式 在耳蜗区和听性脑干中，冲击加速性颅脑损伤最多可达90天。损坏 将对耳蜗核和耳蜗核的传入和传出神经元进行量化。橄榄耳蜗管的作用 传出系统作为IA-TBI期间同时噪声暴露保护效应的一种机制，例如 在车祸中可能会发生什么，将在AIM 2中进行调查。 在安静、嘈杂或虚假的条件下，橄榄耳的反馈将暴露在IA-TBI中，并进行评估 减少了对伤害的听觉后果的保护。免疫组织化学和共聚焦显微镜 将被用来量化毛细胞、传入和传出突触的损伤。免疫组织化学染色 乙酰胆碱酯酶标记和光学显微镜将用于量化轴突数量的变化。 在脑干的听觉区域使用体视学测量。建议的实验结果 将提供对结构和功能后果异质性的根本原因的洞察 作为一种潜在的保护机制，TBI和橄榄耳蜗系统创造了更具生态有效性的 人脑创伤模型。申请者将接受共焦显微镜和光学显微镜的培训， 解剖分析、橄榄耳蜗系统、听性脑干解剖和神经创伤。其他内容 专业发展培训活动和参加地方和国家科学会议是 有计划的。赞助商团队包括具有专业知识和承诺的调查人员，以提高申请者的 培训经验。

Project Summary Auditory dysfunction can occur acutely after brain injuries and continues to change over time after injury. Brain injuries lead to heterogeneity of structural and functional consequences even when the injury is performed identically in a controlled laboratory setting. The effects of brain injuries on auditory system function have not been systematically examined longitudinally in animal models to understand the factors contributing to heterogeneity. The goal of this proposal is to investigate the heterogeneity in auditory functional outcomes after impact acceleration TBI (IA-TBI) or sham conditions and look for underlying structural correlates to injury in the ear and brainstem. In Aim 1, we will evaluate auditory function and corresponding patterns of neurodegeneration in the cochlea and auditory brainstem caused by impact-acceleration TBI up to 90 days after injury. Damage to afferent and efferent neurons in the cochlea and cochlear nucleus will be quantified. The role of the olivocochlear efferent system as a mechanism of protective effects of simultaneous noise exposure during IA-TBI, such as what might occur during a car crash, will be investigated in Aim 2. Subjects with genetically weakened olivocochlear feedback will be exposed to an IA- TBI in quiet or noise or sham conditions and evaluated for decreased protection from the auditory consequences of injury. Immunohistochemistry and confocal microscopy will be used to quantify damage to hair cells, afferent, and efferent synapses. Immunohistochemistry staining and acetylcholinesterase labeling and light microscopy will be used to quantify changes in the number of axons in auditory regions in the brainstem using stereological measurements. The results of the proposed experiments will provide insight into the underlying causes of heterogeneity in the structural and functional consequences of TBI and the olivocochlear system as a potential mechanism for protection to create a more ecologically valid model for human brain trauma. The applicant will receive training in confocal and light microscopy, quantitative anatomical analysis, the olivocochlear system, auditory brainstem anatomy, and neurotrauma. Additional professional development training activities and attendance at local and national scientific conferences are planned. The sponsor team includes investigators with the expertise and commitment to enhance the applicant’s training experience.