The effects of cochlear pericytes and pericyte-related vascular pathology on hearing function

耳蜗周细胞及周细胞相关血管病理对听力功能的影响

• 批准号: 10116361
• 负责人: Xiaorui Shi
• 金额: $ 37.35万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-14 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10116361
• 关键词: 3-Dimensional; Ablation; Action Potentials; Address; Adult; Affect; Afferent Neurons; Aging; Alzheimer' s Disease; Alzheimer' s disease brain; Animal Model; Animals; Auditory; Auditory Brainstem Responses; Autoimmune Inner Ear disease; Blood Vessels; Blood capillaries; Blood flow; Bromodeoxyuridine; Cells; Cellular Stress; Clinical; Cochlea; Communication; Coupled; Data; Dementia; Dendrites; Dependovirus; Ear; Edema; Endothelial Cells; Enhancers; Extravasation; Gene Transfer; Genes; Genetic; Goals; Grant; Growth; Hair Cells; Health; Hearing; Hearing problem; Homeostasis; Hypoxia; Immunoglobulin G; Immunohistochemistry; Impaired cognition; Individual; Infiltration; Inflammation; Investigation; Ions; Knowledge; Labyrinth; Leukocytes; Maintenance; Measures; Mediating; Methods; Microcirculation; Modeling; Nerve Degeneration; Neurodegenerative Disorders; Neurons; Noise; Nuclear; Optics; Organ; Pathologic; Pathology; Pericytes; Phase; Population; Presbycusis; Proliferating; Research; Resolution; Role; Scanning Electron Microscopy; Serotyping; Signal Transduction; Signaling Molecule; Social isolation; Structure; Switch Genes; Techniques; Testing; Therapeutic; Time; Tissues; Transfection; VEGFA gene; Vascular Diseases; Vascular Endothelial Growth Factors; Vascular Permeabilities; Viral Vector; angiogenesis; base; blood perfusion; deafness; density; gene therapy; hair cell regeneration; hearing impairment; hearing restoration; hereditary hearing loss; improved; intravital fluorescence microscopy; macromolecule; microangiography; microvascular pathology; mouse model; neuron loss; normal hearing; novel therapeutics; otoacoustic emission; phenotypic biomarker; progenitor; programs; quantitative imaging; repaired; response; restoration; sound; spiral ganglion; success; vector

PROJECT SUMMARY Hearing loss has a profound impact on individuals, causing communication problems, social isolation, and cognitive decline. Microvascular pathology is a significant factor seen in many types of hearing loss, including sound-induced hearing loss, age-related hearing loss, genetic hearing loss, and autoimmune inner ear disease. Normal capillary blood flow is highly controlled by pericytes. The pericytes, specialized mural cells surrounding small blood vessels adjacent to endothelial cells, are vital for normal vascular function. Pericyte pathology, such as pericyte loss or degeneration, is a significant factor in degenerative neural diseases, including Alzheimer's disease and brain dementia. The cochlear microvasculature contains an abundant population of pericytes. However, the role of pericytes in the cochlea, in general, is understudied. In particular, their roles in vascular and hearing function is largely unknown. Using a combination of well-established and cutting-edge techniques, and building on preliminary data produced under R21 support, the proposed five-year research program continues the investigation of mechanisms outlined in our current R21 grant to further explore the role of PCs, PC-related vascular pathology, and angiogenesis in cochlear health. Success in this project will open new clinical options for treatment of aging-, noise exposure-, and genetic vascular deficiency-related deafness in which PCs are compromised.

项目摘要 听力损失对个人有着深远的影响，导致沟通问题，社会孤立和认知障碍。 下降微血管病变是许多类型听力损失的重要因素，包括声音诱发的听力损失。 听力损失、年龄相关性听力损失、遗传性听力损失和自身免疫性内耳疾病。毛细血管正常 血液流动高度受周细胞控制。周细胞是围绕在小血管周围的特殊壁细胞 与内皮细胞相邻，对正常血管功能至关重要。周细胞病变，如周细胞丢失或 神经退行性疾病，包括阿尔茨海默病和脑退化，是一个重要因素。 痴呆耳蜗微血管含有丰富的周细胞。然而， 耳蜗中的周细胞通常研究不足。特别是，它们在血管和听力功能中的作用是 大部分未知。使用成熟和尖端技术相结合，并在初步 在R21支持下产生的数据，拟议的五年研究计划继续调查 机制概述在我们目前的R21赠款，以进一步探讨PC的作用，PC相关的血管病理， 和耳蜗健康中的血管生成。该项目的成功将为治疗衰老开辟新的临床选择， 噪声暴露和遗传性血管缺陷相关的耳聋，其中PC受损。