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 听觉功能障碍可在脑损伤后急性发生，并在损伤后随时间持续变化。大脑 损伤导致结构和功能后果的异质性，即使在实施损伤时， 在受控的实验室环境中同样地。脑损伤对听觉系统功能的影响还没有 在动物模型中进行了系统的纵向检查，以了解导致 异质性本研究的目的是调查在听觉功能结果的异质性， 冲击加速度TBI（IA-TBI）或假条件下，并寻找潜在的结构相关的伤害， 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 在耳蜗和听觉脑干由冲击加速度TBI造成的损伤后90天。损坏 将量化耳蜗和耳蜗核中的传入和传出神经元。橄榄耳蜗的作用 传出系统作为IA-TBI期间同时噪声暴露的保护作用机制，例如 在汽车碰撞过程中可能发生什么，将在目标2中进行研究。基因缺陷的受试者 橄榄耳蜗反馈将在安静或噪音或假条件下暴露于IA-TBI，并评估 降低对损伤的听觉后果的保护。免疫组织化学和共聚焦显微镜 将用于量化毛细胞、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。拟议实验的结果 将提供深入了解异质性的结构和功能后果的根本原因， TBI和橄榄耳蜗系统作为一种潜在的保护机制， 人类大脑创伤的模型。申请人将接受共聚焦和光学显微镜、定量 解剖分析，橄榄耳蜗系统，听觉脑干解剖和神经创伤。额外 专业发展培训活动和参加地方和国家科学会议， 计划好了申办者团队包括具有专业知识和承诺的研究人员，以提高申请人的 培训经验。