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.

项目概要 听力损失对个人产生深远的影响，导致沟通问题、社交孤立和认知障碍 衰退。微血管病理学是许多类型听力损失的一个重要因素，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。正常毛细血管 血流高度受周细胞控制。周细胞，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。周细胞病理学，例如周细胞丢失或 退行性变是退行性神经疾病的一个重要因素，包括阿尔茨海默病和脑病 失智。耳蜗微脉管系统含有丰富的周细胞群。然而，角色 一般来说，耳蜗中的周细胞尚未得到充分研究。特别是，它们在血管和听力功能中的作用是 很大程度上不为人所知。结合使用成熟和尖端的技术，并在初步基础上 R21支持下产生的数据，拟议的五年研究计划继续调查 我们当前的 R21 拨款中概述的机制，用于进一步探索 PC 的作用、PC 相关的血管病理学、 和耳蜗健康中的血管生成。该项目的成功将为治疗衰老、 噪声暴露和遗传性血管缺陷相关的耳聋，其中 PC 受到损害。