Strial vascular pathology from acoustic trauma

声损伤引起的心房血管病理学

• 批准号: 9383753
• 负责人: Xiaorui Shi
• 金额: $ 42.54万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9383753
• 关键词: Acoustic Trauma; Affect; Afferent Neurons; Aging; Animals; Auditory; Basement membrane; Biological; Biological Preservation; Blood; Blood Vessels; Blood capillaries; Blood flow; Brain; Bromodeoxyuridine; Caliber; Cardiac; Cardiology; Cell Line; Cells; Clinical; Cochlea; Communication; Confocal Microscopy; Development; Disease; Ear; Edema; Electron Microscopy; Employee Strikes; Endothelial Cells; Energy Supply; Exposure to; Extravasation; Failure; Foundations; Functional disorder; Gene Delivery; Goals; Growth Factor; Hair Cells; Health; Hearing; Hearing problem; Heart; Hormones; Human; Hypoxia; Immunophenotyping; Impairment; In Vitro; Individual; Infarction; Injury; Kidney Diseases; Label; Labyrinth; Lateral; Lead; Life; Ligands; Loudness; Maintenance; Mediating; Membrane Proteins; Mesenchymal; Metabolic; Modeling; Molecular; Mus; Myocardial Infarction; Myofibroblast; Natural regeneration; Neonatal; Neurons; Noise; Nuclear; Organ; PDGFA gene; Pathologic; Pathology; Pericytes; Phenotype; Physiology; Platelet-Derived Growth Factor beta Receptor; Population; Production; Proliferating; Property; Proteins; Proto-Oncogene Proteins c-sis; Recovery; Regulation; Reporter; Research; Residual state; Resolution; Retina; Retinal; Role; Sensory; Signal Pathway; Signal Transduction; Site; Social isolation; Source; Stem cells; Stress; Stria Vascularis; Stroke; Structure; Sudden Deafness; System; Testing; Tissues; Transforming Growth Factor beta; Transforming Growth Factors; Transgenic Mice; Transplantation; Trauma; Vascular Diseases; Vascular blood supply; Wound Healing; angiogenesis; base; blood perfusion; capillary; deafness; density; diabetic patient; fibrogenesis; hearing impairment; improved; inhibitor/antagonist; injured; matrigel; migration; network models; neurotrophic factor; novel; novel strategies; pigment epithelium-derived factor; platelet-derived growth factor BB; prevent; protein expression; receptor; repaired; restoration; sound; success; therapeutic target

PROJECT SUMMARY Energy supply to the ear is critical for hearing function since the ear is one of the highest energy consuming organs. Insufficient energy can result from insufficient blood flow to the cochlea contributing to a wide range of clinical hearing disorders such as loud sound-induced hearing loss, hearing loss related to ageing, and sudden deafness, which can largely impact the quality of human life by causing individual communication problems and social isolation. We believe that success in repair and regeneration of hearing function following loss of sensory cells requires parallel restoration or maintenance of an efficient blood supply. The proposed research is part of a longer range study on the role of pericytes in the physiology of the cochlea, but is specifically focused on the pericyte pathology that occurs in loud sound-induced lateral wall microcirculatory dysfunction. Pericytes are multipotent mesenchymal-like cells and are primarily located on microvessels. Normal function of pericytes is vital for blood flow regulation, vascular integrity, angiogenesis and tissue fibrogenesis. Pericyte pathology is profoundly associated with many organ diseases such as brain stroke, heart infarction, and retinal failure. Therapeutic targeting of pericytes has been considered a novel treatment for many of those clinical diseases. Cochlear pericytes are extremely vulnerable and sensitive to damage, but are critical for regulation of cochlear blood flow and maintaining tightness of the blood-labyrinth barrier in the stria vascularis. More specifically they are highly responsive to stress such as acoustic trauma. Upon exposure to loud sound, cochlear pericytes undergo striking changes in their biological properties, but the molecular mechanisms that underline those changes have not yet been studied. In this five year proposal, we will determine what molecular signals lead to loud sound-induced pericyte migration away from the capillaries and their phenotype changes. We will also determine whether transplantation of fresh pericytes such as neo-pericytes (derived from neonatal mice) to noise-damaged cochlea can repair loud sound-damaged microvessels and restore vascular function. The success of each aim will inevitably lead to the development of new protective and restorative therapies for a normal blood flow to cochlea― the critical foundation of hearing preservation or/and restoration.

项目摘要 对耳朵的能量供应对于听力功能是至关重要的，因为耳朵是最高能量消耗之一。 机关能量不足可能是由于流向耳蜗的血流不足导致的，从而导致大范围的听力损失。 临床听力障碍，如响亮的声音引起的听力损失，与衰老有关的听力损失，以及突发性听力损失。 耳聋，会导致个人沟通问题，从而在很大程度上影响人类的生活质量 和社会孤立。我们相信，在听力损失后， 感觉细胞需要平行恢复或维持有效的血液供应。拟议研究 这是一项关于周细胞在耳蜗生理学中作用的长期研究的一部分，但具体来说， 集中在周细胞病理发生在响亮的声音引起的侧壁微循环功能障碍。 周细胞是多能间充质样细胞，主要位于微血管上。正常功能 周细胞对于血流调节、血管完整性、血管生成和组织纤维形成至关重要。周细胞 病理学与许多器官疾病如脑中风、心脏梗塞和视网膜病变密切相关。 失败周细胞的治疗性靶向已经被认为是许多那些临床病症的新治疗方法。 疾病皮质周细胞对损伤极其脆弱和敏感，但对于调节至关重要 耳蜗血流量和维持血管纹中血迷路屏障的紧密性。更 特别地，它们对应力如声损伤高度敏感。一旦暴露在巨大的声音中， 耳蜗周细胞的生物学特性发生了显著的变化，但 强调这些变化尚未得到研究。在这个五年计划中，我们将确定 分子信号导致高声诱导的周细胞迁移远离毛细血管及其表型 变化我们还将确定是否移植新鲜周细胞，如新生周细胞（来源于 新生小鼠）对噪声损伤耳蜗的作用可以修复高声损伤的微血管， 功能每个目标的成功将不可避免地导致新的保护性和恢复性的发展。 耳蜗血流正常的治疗-听力保护或/和恢复的关键基础。