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

项目总结 听力损失对个人有深远的影响，会导致沟通问题、社会孤立和认知 拒绝。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。正常毛细血管 血液流动受到周细胞的高度控制。周细胞，环绕小血管的特化壁细胞 与血管内皮细胞相邻，对正常的血管功能至关重要。周细胞病理，如周细胞丢失或 变性是退行性神经疾病的一个重要因素，包括阿尔茨海默病和大脑 痴呆症。耳蜗微血管系统含有大量的周细胞。然而，它的作用是 总体而言，耳蜗周细胞的研究还不够深入。特别是，它们在血管和听力功能中的作用是 很大程度上是未知的。使用成熟和尖端技术的组合，并在初步的基础上 在R21支持下产生的数据，拟议的五年研究方案继续调查 在我们目前的R21拨款中概述的机制，以进一步探索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-- 噪音暴露和遗传性血管缺陷相关的耳聋，其中PC受到损害。

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.