COCHLEAR MACROPHAGES AND EPITHELIAL REPAIR

耳蜗巨噬细胞和上皮修复

• 批准号: 9899241
• 负责人: Keiko Hirose
• 金额: $ 32.41万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-15 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9899241
• 关键词: Affect; Animals; Auditory Threshold; Bacteria; Bacterial Infections; Bacterial Meningitis; Blood; Blood - brain barrier anatomy; Blood Circulation; Blood Vessels; Bone remodeling; Brain; Cells; Cerebrospinal Fluid; Cicatrix; Cochlea; Cochlear Implants; Cochlear implant procedure; Environment; Epithelial; Epithelium; Fibrosis; Functional disorder; Goals; Grant; Health; Hearing; Immune; Immune response; Immune system; Implant; Infection; Infectious Agent; Inflammation; Inflammatory; Inflammatory Response; Injury; Inner Ear Infection; Ions; Knock-out; Labyrinth; Lead; Leukocytes; Life; Liquid substance; Maintenance; Measures; Meningitis; Methods; Nutrient; Organ; Osteoclasts; Osteogenesis; Oxygen; Patients; Pericytes; Perilymph; Permeability; Personal Satisfaction; Pharmaceutical Preparations; Physiologic Ossification; Play; Proteins; Regulation; Research; Role; Sampling; Sensory; Series; Signal Transduction; Stream; Streptococcus pneumoniae; Testing; Time; Tissues; Treatment Effectiveness; Vascular Permeabilities; Water; Wild Type Mouse; Work; bone; cell type; chemokine; chemokine receptor; deaf; deafness; design; experimental study; hearing impairment; hearing loss treatment; hearing preservation; improved; injured; macrophage; monocyte; permanent hearing loss; prevent; prevent hearing loss; public health relevance; repaired; solute; tool

 DESCRIPTION (provided by applicant): In the inner ear, the blood vessels that carry oxygen and nutrients to the hearing cells are carefully regulated so that fluids inside the blood vessel d not leak into the tissues of the inner ear. This separation between contents of the blood and contents of the inner ear is called the blood-perilymph barrier. This barrier regulates the immune system and controls the traffic of white blood cells from the blood stream into the organs. When the immune system is activated, white blood cells can leave the vessels, enter the target organ and eliminate harmful bacteria or unwanted cells, but at the same time, it can damage healthy tissues that were not the intended targets. Therefore, careful regulation of this barrier and the immune response are very important. Under certain conditions, when the barrier becomes leaky, fluids and solutes from the blood vessels mix with the inner ear fluids, and this mixing is believed to cause hearing loss, although this has not been proven. In our first series of experiments, we will determine how vessel permeability affects hearing. Our goal is to understand how disruption of this barrier influences hearing levels and how it can be repaired and hearing be retained. Our second series of studies will focus on the role of specific white blood cells that enter the cochlea during meningitis. Meningitis is a life-threatening infection of the spinal fluid and inner ear fluid where the blood-perilymph barrier and the blood-brain barrier are severely compromised. Meningitis is commonly associated with permanent hearing loss and sometimes with cochlear ossification, where new bone forms in the spaces that are normally fluid-filled. Cochlear ossification is a major concern because cochlear implants, which are our best tool for treating deafness, often cannot be placed when the space for the implant is filled with bone. We believe that the immune response to infection results in this new bone formation and contributes to hearing loss. Although the immune response is essential to eliminate the infection in meningitis, better control of the immune response may result in preserved hearing. If we could prevent the loss of hearing in patients with meningitis and prevent the formation of new bone in the cochlea after meningitis, it would greatly help the well being of people who are affected by this condition. The overall goals of this grant are to improve our understanding of how the immune system interacts with the inner ear environment, what parts of the immune system are beneficial, such as preventing or eliminating infections, and which of its functions might be harmful. Because many current therapies for hearing loss involve the use of medications that suppress the immune system, it is important to understand how the immune system works in the inner ear, to design better medications and improve the effectiveness of treatment for hearing loss.

 描述(申请人提供)：在内耳中，将氧气和营养物质输送到听力细胞的血管受到仔细的调节，使血管内的液体不会泄漏到内耳的组织中。血液内容物和内耳内容物之间的这种分离称为血-外淋巴屏障。这种屏障调节免疫系统，并控制白细胞从血液流向器官的运输。当免疫系统被激活时，白细胞可以离开血管，进入靶器官，清除有害细菌或多余的细胞，但与此同时，它可能会损害不是预定目标的健康组织。因此，仔细调节这一屏障和免疫反应是非常重要的。在某些情况下，当屏障变得漏水时，来自血管的液体和溶质与内耳液混合，这种混合被认为会导致听力损失，尽管这一点尚未得到证实。在我们的第一系列实验中，我们将确定血管渗透性如何影响听力。我们的目标是了解这种障碍的破坏如何影响听力水平，以及如何修复和保留听力。我们的第二个系列研究将集中在脑膜炎期间进入耳蜗的特定白细胞的作用。脑膜炎是一种危及生命的脑膜炎 血液外淋巴屏障和血脑屏障严重受损的脊髓液和内耳液。脑膜炎通常与永久性听力损失有关，有时还与耳蜗骨化有关，在正常情况下充满液体的空间中会形成新的骨骼。耳蜗骨化是一个主要的问题，因为人工耳蜗是我们治疗耳聋的最好工具，当植入物的空间被骨头填满时，往往无法放置。我们认为，对感染的免疫反应导致了这种新骨形成，并导致了听力损失。虽然免疫反应对于消除脑膜炎的感染是必不可少的，但更好地控制免疫反应可能会导致听力得到保护。如果我们能预防脑膜炎患者的听力损失，并防止脑膜炎后耳蜗骨的新骨形成，将极大地帮助受这种疾病影响的人的福祉。这笔赠款的总体目标是提高我们对免疫系统如何与内耳环境相互作用的理解，免疫系统的哪些部分是有益的，如预防或消除感染，以及它的哪些功能可能是有害的。由于目前许多听力损失的治疗方法都涉及使用抑制免疫系统的药物，因此了解免疫系统在内耳中的工作原理、设计更好的药物并提高听力损失治疗的有效性是很重要的。