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

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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.