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:
- 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 MembraneCell DeathCellsClinicalClinical TrialsCochleaCochlear ductDataDendritesDiameterEndolymphEndolymphatic 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 damageneuralnoise exposurenoise traumapermanent hearing losspressureprevent hearing lossresponseribbon 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/摘要
大约15%的美国人因噪音暴露而听力损失。经典的解释是对人的创伤
耳蜗毛细胞噪声引起的听力损失的另一种机制是耳蜗突触病。那里
临床上还没有有效的治疗方法来预防创伤性噪音后通过这两种机制造成的听力损失
exposure.最近,我们发现内淋巴积水发生在爆炸或噪音创伤后,
内淋巴积水与耳蜗突触病相关。我们的中心假设是内淋巴管
水肿是响应谷氨酸而发生的听神经树突肿胀的替代标志物
兴奋性毒性我们将以三个目标来检验这一假设。首先,我们将确定是否肿胀的听觉
神经树突与内淋巴积水有关。我们将测量活体中阶的体积
使用体积光学相干断层扫描和振动测量(VOCTV)。我们将同时想象
用双光子显微镜观察在体听神经纤维终末并测量其直径。二是
确定急性毛细胞功能障碍是否是产生以下生理后果所必需的:
耳蜗突触病我们将使用VOCTV测量基底膜振动调谐曲线,以评估
耳蜗生理学我们还将测量波1听觉脑干反应(ABR)峰-峰
振幅以评估听觉神经生理学。第三,我们将确定是否煽动机制,
耳蜗突触病是谷氨酸、内淋巴积水或树突肿胀。我们将测量scala
噪声或低渗刺激后受损小鼠的中膜容积、耳蜗增益和突触计数
转导或受损的谷氨酸释放在IHC-听觉神经突触。因此,我们建议
证明或反驳我们的假设此外,我们将了解生理后果
以及内淋巴水肿和突触病的机制。
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:
10307056 - 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:
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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