INNER EAR FLUID INTERACTIONS

这项建议的目标是建立如何内淋巴组成和 量是有规律的。缺乏这方面的知识严重限制了我们的 了解汽车内部的疾病过程，如梅尼埃的 疾病和外淋巴瘘。多年来，我们一直是 研究内耳液的新技术的发展。标记 离子电渗，无容量干扰，进入内耳液， 它们的运动由离子选择性微电极监测。这些 技术已经允许横截面积和纵向 耳蜗流体的运动在体内被准确地量化。对于一些 我们已经知道，在正常的耳蜗中， 耳蜗液流动非常缓慢我们现在发现当内淋巴 体积受到干扰时，确实会发生纵向运动， 显着贡献的离子变化的内淋巴。第一个目标 本项目的目的是表征内淋巴面积的依赖性， 机械因素的变化和纵向运动，如压力 和音量干扰。然后我们会评估 耳蜗中离子转运过程的药理学操作 导致面积或流量变化。类似的措施将在 内淋巴囊已消融的动物，以评估 该结构在内淋巴体积调节中的作用。病理生理学 水肿发展的初始阶段将在 详细此外，磁共振（MR）显微镜将用于 生成耳蜗流体空间的精确三维重建， 各种实验条件。这些解剖数据将提供 耳蜗液内稳态过程的数字模型的基础， 这将用于优化实验设计和生成 对结果进行准确的定量解释。我们将相互关联 解剖测量、流量和面积的物理测量以及化学测量 测量电解质成分和耳蜗功能。 只有了解机械、化学和 生理过程，我们是否有希望了解内淋巴体积是如何 以及如何治疗患者的容量紊乱。

The goal of this proposal is to establish how endolymph composition and volume are regulated. Lack of knowledge in this area severely limits our understanding of disease processes of the inner car, such as Meniere's disease and perilymph fistula. For a number of years, we have pioneered the development of novel techniques to study inner ear fluids. Markers are iontophoresed, without volume disturbance, into the inner ear fluids and their movements monitored by ion-selective microelectrodes. These techniques have allowed the cross-sectional area and longitudinal movements of cochlear fluids to be accurately quantified in vivo. For some time, we have known that in the normal cochlea, longitudinal movements of cochlear fluids are extremely slow. We have now found that when endolymph volume is disturbed, longitudinal movements do occur which make a significant contribution to the ionic changes in endolymph. The first aim of this project is to characterize the dependence of endolymph area changes and longitudinal movements on mechanical factors, such as pressure and volume disturbances. We will then assess whether or not pharmacological manipulations of ion transport processes in the cochlea result in area or flow changes. Comparable measures will be made in animals in which the endolymphatic sac has been ablated, to assess the role of this structure in endolymph volume regulation. The pathophysiology of the initial stages of hydrops development will be investigated in detail. In addition, magnetic resonance (MR) microscopy will be used to generate accurate 3-D reconstructions of the cochlear fluid spaces under a variety of experimental conditions. These anatomic data will provide the basis for numeric models of homeostatic processes in the cochlear fluids, which will be used to optimize experimental design and to generate accurate quantitative interpretation of findings. We will correlate anatomic measures, physical measures of flow and area, and chemical measures of electrolyte composition with measures of cochlear function. Only by understanding the relationships between mechanical, chemical and physiological processes, can we hope to understand how endolymph volume is regulated and how disturbances of volume can be treated in patients.