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Mechanisms of cochlear synaptopathy after noise or blast trauma

噪声或爆炸损伤后耳蜗突触病的机制

基本信息

批准号：
10540702
负责人：
John S Oghalai
金额：
$ 57.44万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-01-01 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10540702
关键词：
Acoustic Nerve Acute Affect American Anatomy Auditory Auditory Brainstem Responses Auditory Threshold Basilar Membrane Cell Death Cells Clinical Clinical Trials Cochlea Cochlear duct Data Dendrites Diameter Endolymph Endolymphatic Hydrops Exposure to Functional disorder Glutamates Hair Cells Hour Image Immunohistochemistry Impairment Ions Loudness Measures Metabolic Methodology Mus Nerve Fibers Neurons Neurotransmitters Noise Noise-Induced Hearing Loss Optical Coherence Tomography Pathway interactions Pattern Physiological Physiology Presynaptic Terminals Research Residual state SLC17A8 gene Saline Signal Transduction Surrogate Markers Swelling Synapses Testing Time Transmission Electron Microscopy Trauma Water base blast trauma cochlear synaptopathy effective therapy excitotoxicity extracellular hearing impairment hidden hearing loss human subject in vivo in vivo imaging innovation mechanical energy nerve damage neural noise exposure noise trauma permanent hearing loss pressure prevent hearing loss response ribbon synapse sound two photon microscopy

项目摘要

Project Summary/Abstract About 15% of Americans have hearing loss due to noise exposure. The classical explanation is trauma to the cochlear hair cells. An additional mechanism of noise-induced hearing loss is cochlear synaptopathy. There are no effective treatments used clinically to prevent hearing loss via either mechanism after traumatic noise exposure. Recently, we identified that endolymphatic hydrops occurs after blast or noise trauma, and that endolymphatic hydrops correlated with cochlear synaptopathy. Our central hypothesis is that endolymphatic hydrops is a surrogate marker for swelling of auditory nerve dendrites that occurs in response to glutamate excitotoxicity. We will test this hypothesis with three aims. First, we will determine whether swelling of auditory nerve dendrites correlates with endolymphatic hydrops. We will measure the volume of scala media in vivo using volumetric optical coherence tomography and vibrometry (VOCTV). We will simultaneously image auditory nerve fiber terminals in vivo with two-photon microscopy and measure their diameter. Second, we will determine whether acute hair cell dysfunction is necessary to produce the physiological consequences of cochlear synaptopathy. We will measure basilar membrane vibratory tuning curves using VOCTV to assess cochlear physiology. We will also measure the wave 1 auditory brainstem response (ABR) peak-to-peak amplitude to assess auditory nerve physiology. Third, we will determine whether the inciting mechanism of cochlear synaptopathy is glutamate, endolymphatic hydrops, or dendritic swelling. We will measure scala media volume, cochlear gain, and synaptic counts after noise or hypotonic challenge in mice with impaired transduction or impaired glutamate release at the IHC-auditory nerve synapse. Therefore, we are proposing to definitively prove or disprove our hypothesis. Furthermore, we will understand the physiological consequences and mechanisms of endolymphatic hydrops and synaptopathy.

项目总结/文摘