Diagnosing outer hair cell health along the cochlear partition

诊断耳蜗分区外毛细胞的健康状况

• 批准号: 8460625
• 负责人: MARK E CHERTOFF
• 金额: $ 25.22万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-15 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8460625
• 关键词: Acoustic Nerve; Action Potentials; Analysis of Variance; Anatomic Sites; Anatomic structures; Anatomy; Animal Model; Animals; Apical; Auditory; Auditory Brainstem Responses; Basilar Membrane; Behavioral; Beryllium; Boxing; Cells; Chinchilla (genus); Clinic; Clinical Trials; Cochlea; Data; Development; Diagnosis; Diagnostic; Diagnostic Procedure; Diagnostic tests; Electrodes; Engineering; Equation; Etiology; Europe; External auditory canal; Fetal Tissue Transplantation; Frequencies; Future; Genetic; Gentamicins; Goals; Graph; Gray unit of radiation dose; Growth; Hair Cells; Health; Hearing; Histology; Human; Inner Hair Cells; Intervention; Labyrinth; Length; Lesion; Localized Lesion; Location; Manuscripts; Masks; Measurement; Measures; Medical; Movement; Nerve Fibers; Noise; Noise-Induced Hearing Loss; Operative Surgical Procedures; Outcome; Outer Hair Cells; Patients; Phase; Physicians; Physiological; Physiology; Population; Positioning Attribute; Probability; Procedures; Promontory; Rehabilitation therapy; Relative (related person); Reporting; Research; Review Literature; Sensorineural Hearing Loss; Shapes; Signal Transduction; Solid; Stimulus; Stria Vascularis; Structure; Sum; Techniques; Testing; Therapeutic; Therapeutic Agents; Therapeutic Intervention; Time; TimeLine; Tissue Transplantation; Transducers; Translating; Tympanic membrane; United States; Width; base; cell injury; clinical practice; density; hair cell regeneration; hearing impairment; improved; indexing; notch protein; novel diagnostics; receptor; research study; response; round window; statistics; success; tool; treatment strategy; voltage

Sensorineural hearing loss results from damage to a variety of structures within the cochlea and auditory nerve. Presently, genetic and tissue transplantation strategies are being explored as therapeutic strategies for curing hearing loss. Unfortunately there are no available diagnostic techniques that isolate and distinguish the anatomic site(s) of damage within the cochlea or auditory nerve. A test battery that identifies the locus of lesion(s) will allow physicians to target the appropriate anatomic sites for medical intervention. The long-term goal of this research is to develop these diagnostic tests. In this proposal, the aim of the R21 phase is to determine if the cochlear microphonic (CM), in response to a low-frequency tone embedded in high-pass noise, can be used to quantify the location of missing outer hair cells along the cochlear partition. A cumulative distribution function (CDF) of outer hair cells is obtained by plotting the amplitude of the masked CM relative to the unmasked amplitude for specific masker frequencies. We hypothesize that the location of a plateau in the CDF (or some other variable in the CDF or corresponding probability density function) will relate to the location of missing outer hair cells. This is tested by correlating the location of missing outer hair cells estimated by the CDF with anatomic measurements in animals with hair cell lesions. In clinic populations, outer hair cells may be present but functioning abnormally. In the R33 phase we develop indices from hair cell transducer functions to determine the health of surviving outer hair cells. We hypothesize that 1) transducer function indices can be obtained along the length of the cochlea and 2) the indices can quantify outer hair cell health despite damage to other cochlear structures. The first goal is tested by correlating the location of the plateau of the CDF of an index with the location of maximum hearing loss in animals with temporary hearing loss at various frequencies. The second hypothesis is examined by comparing indices among groups of animals with lesions to outer hair cells and other structures. The studies in this proposal are likely to be translated to human patients. Presently, the CM is recorded in Audiologic clinics in the United States and Europe. Future studies optimizing stimuli and recording location are envisioned as the next step for developing diagnostic tests that compliment the new medical treatment strategies that are being explored to cure sensorineural hearing loss.

感官听力损失导致耳蜗和听觉内各种结构的损坏导致 神经。目前，正在探索遗传和组织移植策略作为治疗策略 治愈听力损失。不幸的是，没有可用的诊断技术可以隔离和区分 耳蜗或听觉神经内损伤的解剖部位。标识的测试电池 病变将使医生可以针对适当的解剖部位进行医疗干预。长期 这项研究的目标是开发这些诊断测试。在此提案中，R21阶段的目的是 确定耳蜗微音（CM）是否响应于嵌入高通的低频音调 噪声可用于量化人工耳蜗沿线缺失的外毛细胞的位置。累积 外毛细胞的分布函数（CDF）是通过绘制蒙版CM的幅度而获得的 特定掩蔽频率的未掩盖振幅。我们假设高原在 CDF（或CDF中的其他一些变量或相应的概率密度函数）将与该位置有关 缺失的外毛细胞。通过将缺失外毛细胞的位置相关联 CDF具有毛细胞病变动物的解剖测量。在诊所种群中，外毛细胞可能 存在但异常起作用。在R33阶段，我们从毛细胞传感器开发指标 功能以确定存活的外毛细胞的健康。我们假设1）传感器函数 可以沿耳蜗的长度获得指数，2）指数可以量化外毛细胞健康 尽管损坏了其他耳蜗结构。第一个目标是通过将高原的位置关联来测试 索引的CDF的最大听力损失的位置 各种频率。通过比较动物组之间的指标与 病变对外毛细胞和其他结构。 该提案中的研究可能会转化为人类患者。目前，CM记录在 美国和欧洲的听力诊所。未来的研究优化刺激和记录位置是 设想是开发诊断测试的下一步，以补充新的医疗 正在探索以治愈感官听力损失的策略。