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

冲击加速脑损伤的听觉后果的结构功能模型评估以及通过橄榄耳蜗系统的保护

• 批准号: 10605573
• 负责人: Kali Burke
• 金额: $ 6.76万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10605573
• 关键词: Acceleration; Acetylcholinesterase; Acoustics; Acute; Address; Adolescent; Adult; Afferent Neurons; Air Bags; Anatomy; Animal Model; Animals; Auditory; Auditory Brainstem Responses; Auditory system; Axon; Brain; Brain Injuries; Brain Stem; Cell Nucleus; Clinic; Clinical; Clinical assessments; Cochlea; Cochlear nucleus; Confocal Microscopy; Craniocerebral Trauma; Data; Development; Ear; Efferent Neurons; Environmental Risk Factor; Evaluation; Event; Experimental Designs; Exposure to; Feedback; Fiber; Financial compensation; Foundations; Goals; Hair Cells; Health; Hearing problem; Heterogeneity; Human; Immunohistochemistry; Individual; Injury; Intrinsic factor; Knock-out; Label; Laboratories; Lead; Link; Loudness; Measurement; Measures; Methods; Modeling; Mus; Nerve Degeneration; Nervous System Trauma; Neuroanatomy; Neurobiology; Nicotinic Receptors; Noise; Outcome; Outcome Measure; Pathology; Patients; Pattern; Physiological; Process; Reporting; Research; Research Personnel; Role; Severities; Site; Source; Stains; Stimulus; Structure; Structure-Activity Relationship; Synapses; System; Testing; Therapeutic; Time; Training; Training Activity; Traumatic Brain Injury; Vehicle crash; Whiplash Injuries; auditory pathway; automobile accident; design; experience; experimental study; functional loss; functional outcomes; head impact; hearing impairment; individual variation; insight; light microscopy; noise exposure; protective effect; relating to nervous system; repaired; response; screening; simulation; sound; symposium

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.

项目摘要 听觉功能障碍可能会在脑损伤后急性发生，并在受伤后随着时间的推移继续改变。脑 伤害导致结构和功能后果的异质性，即使受伤 在受控的实验室环境中相同。脑损伤对听觉系统功能的影响尚未 在动物模型中进行了系统的纵向检查，以了解导致的因素 异质性。该提案的目的是调查听觉功能结果的异质性 撞击加速度TBI（IA-TBI）或假条件，并寻找与损伤的潜在结构相关 耳朵和脑干。在AIM 1中，我们将评估听觉功能和神经变性的相应模式 在受伤后90天内，由冲击加速器TBI引起的耳蜗和听觉脑干。损坏 耳蜗和人工耳蜗中的传入神经元将被量化。橄榄石的作用 有效的系统是IA-TBI期间简单噪声暴露的保护作用机制，例如 车祸期间可能发生的事情将在AIM 2中进行调查。 橄榄石反馈将在安静或噪音或假条件下暴露于iatbi，并评估 减少了免受受伤后果的保护。免疫组织化学和共聚焦显微镜 将用于量化对毛细胞，传入和有效突触的损害。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 在脑干中的听觉区域中，使用立体量测量。提出的实验的结果 将洞悉在结构和功能后果中的异质性的根本原因 TBI和橄榄石系统是保护更生态有效的潜在机制 人脑创伤的模型。申请人将接受共焦和光学显微镜，定量的培训 解剖学分析，橄榄石系统，听觉脑干解剖结构和神经曲。额外的 专业发展培训活动和在当地和国家科学会议上的出席是 计划。赞助商团队包括具有专业知识和承诺的调查员，以增强申请人的 培训经验。