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

基本信息

批准号：
10222652
负责人：
Brent Allen Wilkerson
金额：
$ 15.06万
依托单位：
MEDICAL UNIVERSITY OF SOUTH CAROLINA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-16 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10222652
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 Epithelial Etiology Exhibits Extravasation Functional disorder Future Gender Gene Expression Profile Gene set enrichment analysis 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 Process Proteins Regression Analysis Research Risk Factors Role Sensorineural Hearing Loss Smoking Stria Vascularis Structure Techniques Testing Therapeutic Thrombosis Tissues Vascular Diseases Vasodilation Veterans Wild Type Mouse aminoglycoside-induced ototoxicity angiogenesis curative treatments density differential expression efficacy evaluation endothelial stem cell hearing impairment improved inner ear diseases inner ear injury innovation offspring otoprotectant ototoxicity overexpression preventive intervention progenitor repaired single-cell RNA sequencing solute statistics vascular abnormality

项目摘要

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. !

项目概要感音神经性听力损失通常与血管纹中的脉管系统变性有关，这是一种听力功能所需的耳蜗侧壁的血管化上皮。然而，萎缩仍然难以捉摸，并且不存在治疗或预防干预措施。增强或“正常化”耳蜗血管功能可能会减缓或逆转血管纹萎缩：1）受影响小鼠的纹状体萎缩与血管纹有关血管纹异常和血管完整性丧失，2) 改善内皮屏障功能、血管张力和血管生成可保护小鼠免受氨基糖苷类诱导的纹状体萎缩。为了测量这些变化，该方法使用创新技术来比较正常和受伤的内脏耳朵，脉管系统的形态，包括整个耳蜗中的微血管的 3D 以及分子因此，除了测试上述预测之外，这项研究可以识别对细胞亚型、分子机制和结构具有潜在意义的耳蜗中的循环和溶质运输，这对于理解和管理具有广泛的影响内耳疾病。！