Cochlear Vasculature and Its Role in Strial Atrophy

耳蜗脉管系统及其在纹状体萎缩中的作用

• 批准号: 9813369
• 负责人: Brent Allen Wilkerson
• 金额: $ 15.55万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-16 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9813369
• 关键词: 3-Dimensional; Affect; Age; Aging; Aminoglycosides; Apolipoprotein A-I; Atrophic; Auditory Brainstem Responses; Beavers; Blood Circulation; Blood Vessels; Blood capillaries; Blood flow; Caliber; Cardiovascular Diseases; Cell Count; Cells; Centers for Disease Control and Prevention (U.S.); Child; Cluster Analysis; Cochlea; Diabetes Mellitus; Diabetic Retinopathy; Dyes; Dyslipidemias; Endothelial Cells; Endothelium; Epithelium; Etiology; Exhibits; Extravasation; Functional disorder; Future; Gender; Gene Expression Profile; Genes; Hair Cells; Hearing; High Density Lipoproteins; Hypertension; Injury; Ischemia; Kanamycin; Labyrinth; Lateral; Ligaments; Linear Regressions; Measures; Mediating; Microspheres; Modeling; Molecular; Morphology; Mouse Strains; Mus; Noise; Obesity; Oxidative Stress; Pathogenicity; Pathologic; Pathology; Pathway interactions; Pattern; Perfusion; Pharmacology; Population; Presbycusis; Preventive Intervention; Process; Proteins; Regression Analysis; Research; Risk Factors; Role; Sensorineural Hearing Loss; Smoking; Stem cells; Stria Vascularis; Structure; Techniques; Testing; Therapeutic; Thrombosis; Tissues; Vascular Diseases; Vasodilation; Veterans; aminoglycoside-induced ototoxicity; angiogenesis; curative treatments; density; differential expression; hearing impairment; improved; injured; inner ear diseases; innovation; offspring; otoprotectant; ototoxicity; overexpression; progenitor; repaired; single-cell RNA sequencing; solute; statistics; vascular abnormality

PROJECT SUMMARY Sensorineural hearing loss is often associated with degeneration of the vasculature in the stria vascularis, a vascularized epithelium in the lateral wall of the cochlea required for hearing function. The mechanism for strial atrophy remains elusive, however, and no curative or preventative interventions exist. This research tests two predictions of the hypothesis that augmenting or “normalizing” vascular function in the cochlea may slow or reverse atrophy in the stria vascularis: 1) that strial atrophy in affected mice is associated with vascular abnormalities and loss of vascular integrity in the stria vascularis and 2) that improved endothelial barrier function, vascular tone and angiogenesis protects mice against aminoglycoside-induced strial atrophy. To measure such changes, the approach uses innovative techniques to compare, in normal and injured inner ears, the morphology of vasculature including microvessels in the whole cochlea in 3D as well as the molecular makeup of the cochlear vasculature at the single cell level. Thus, in addition to testing the predictions above, this research could identify cell subtypes, molecular mechanisms and structures of potential significance to circulation and solute transport in the cochlea, which has broad implications for understanding and managing inner ear disease. !

项目摘要 感音神经性听力损失通常与血管纹中的血管变性有关， 耳蜗外侧壁上的血管化上皮，是听觉功能所需的。该机制用于 然而，萎缩仍然难以捉摸，并且不存在治疗性或预防性干预措施。这项研究测试了两个 增强或“正常化”耳蜗中的血管功能可能减缓或 逆转血管纹萎缩：1）受影响小鼠的血管纹萎缩与血管 血管纹中血管完整性的异常和丧失，以及2）改善内皮屏障 功能、血管张力和血管生成保护小鼠免受氨基糖苷类诱导的血管萎缩。到 测量这种变化，该方法使用创新的技术来比较，在正常和受伤的内部 耳，包括微血管在内的整个耳蜗的三维血管形态以及分子生物学特征。 在单细胞水平上的耳蜗脉管系统的组成。因此，除了测试上述预测外， 这项研究可以确定细胞亚型，分子机制和结构的潜在意义， 循环和溶质运输在耳蜗，这对理解和管理广泛的影响 内耳疾病 !