INNER EAR FLUID INTERACTIONS

这项提议的目标是确定内淋巴的组成和 音量是有调节的。缺乏这方面的知识严重限制了我们 对内车疾病过程的理解，如梅尼埃病 疾病和外淋巴瘘。多年来，我们一直在开拓 研究内耳液的新技术的发展。标记是 离子漂浮，没有音量干扰，进入内耳液和 它们的运动由离子选择性微电极监测。这些 技术允许横截面面积和纵向 在活体内准确量化耳蜗液的运动。对一些人来说 时间，我们已经知道在正常的耳蜗里， 耳蜗液的速度非常慢。我们现在发现，当内淋巴 音量受到干扰时，确实会发生纵向运动，从而使 对内淋巴中的离子变化有显著贡献。第一个目标 这个项目的目的是刻画内淋巴区域的依赖性 机械因素的变化和纵向运动，如压力 以及音量扰动。然后我们将评估是否 耳蜗内离子转运过程的药理学调控 导致面积或流量的变化。将在#年制定可比措施 内淋巴囊已被消融的动物，以评估 这种结构在内淋巴体积调节中的作用。病理生理学 将在#年调查注水开发的初始阶段的 细节。此外，磁共振(MR)显微镜将用于 生成精确的耳蜗液空间的三维重建 各种实验条件。这些解剖数据将为 耳蜗液内稳态过程的数值模型基础， 它将用于优化实验设计和生成 对调查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 电解液成分测量和耳蜗术后功能测量。 只有通过理解机械、化学和化学之间的关系 生理过程，我们能希望了解内淋巴体积是多少 以及如何治疗患者的音量紊乱。

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.