Mechanisms of cochlear synaptopathy after noise or blast trauma
噪音或爆炸创伤后耳蜗突触病的机制
基本信息
- 批准号:10307056
- 负责人:
- 金额:$ 57.44万
- 依托单位:
- 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:
- 关键词:Acoustic NerveAcuteAffectAmericanAnatomyAuditoryAuditory Brainstem ResponsesAuditory ThresholdBasilar MembraneCaliberCell DeathCellsClinicalClinical TrialsCochleaCochlear ductDataDendritesEndolymphEndolymphatic HydropsExposure toFunctional disorderGlutamatesHair CellsHourImageImmunohistochemistryImpairmentIonsLoudnessMeasuresMetabolicMethodologyMusNerve FibersNeuronsNeurotransmittersNoiseNoise-Induced Hearing LossOptical Coherence TomographyPathway interactionsPatternPhysiologicalPhysiologyPresynaptic TerminalsResearchResidual stateSLC17A8 geneSalineSignal TransductionSurrogate MarkersSwellingSynapsesTestingTimeTransmission Electron MicroscopyTraumaWaterbaseblast traumacochlear synaptopathyeffective therapyexcitotoxicityextracellularhearing impairmenthidden hearing losshuman subjectin vivoin vivo imaginginnovationmechanical energynerve damagenoise exposurenoise traumapermanent hearing losspressureprevent hearing lossrelating to nervous systemresponseribbon synapsesoundtwo 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
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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John S Oghalai其他文献
John S Oghalai的其他文献
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{{ truncateString('John S Oghalai', 18)}}的其他基金
Otolaryngology Clinician-Scientist Training Program
耳鼻喉科临床医生科学家培训计划
- 批准号:
10649406 - 财政年份:2022
- 资助金额:
$ 57.44万 - 项目类别:
Otolaryngology Clinician-Scientist Training Program
耳鼻喉科临床医生科学家培训计划
- 批准号:
10291583 - 财政年份:2022
- 资助金额:
$ 57.44万 - 项目类别:
Mechanisms of cochlear synaptopathy after noise or blast trauma
噪音或爆炸创伤后耳蜗突触病的机制
- 批准号:
10053337 - 财政年份:2020
- 资助金额:
$ 57.44万 - 项目类别:
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
- 批准号:
10540702 - 财政年份:2020
- 资助金额:
$ 57.44万 - 项目类别:
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
- 批准号:
9887606 - 财政年份:2020
- 资助金额:
$ 57.44万 - 项目类别:
Optical coherence tomography for 3D measures of cochlear mechanics in vivo
用于体内耳蜗力学 3D 测量的光学相干断层扫描
- 批准号:
9454168 - 财政年份:2015
- 资助金额:
$ 57.44万 - 项目类别:
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