HUMAN MODEL OF VESTIBULAR DEAFFERENTATION

这项提案的长期目标是开发人类模型， 通过形态学和神经化学研究， 继发于前庭周围特定病变的变化。 本研究采用了两种模型：一、损伤Scarpa神经节 和II：影响终末器官的病变。 结合了古典 组织学技术，免疫组织化学，电子显微镜， 分子生物学技术和计算机定量 分析将用于记录这些变化。 的一个独特方面 本发明建议是，多种人类颞骨 和脑干标本可用于本研究，包括 尸检、档案和手术标本。 本研究将侧重于 来自慢性代偿状态患者的样本， 前庭周围病变。 关于以下人体现象的关键信息 前庭周边将获得：1）是否有依赖性的 前庭神经上皮对前庭神经的存活有什么影响？ （二） 前庭神经依赖于前庭毛吗 细胞生存？ 3)逆行性变性是否发生在 存在完整的传入树突吗 4)有没有一种亚型 Calretinin免疫反应的Scarpa~s神经节神经元， 逆行性退化吗 5)是否存在定性的相关性 终末器官的退化程度和斯卡帕的退化程度 神经节？ 在前庭核复合体（VNC）内，将记录重要数据 会议地点： 1)退行性变是否影响中枢神经系统 前庭神经损伤后前庭神经的突起 外围？ 2)是否有突触密度的永久性损失， Scarpa神经节和/或 器官？ 3)是否有谷氨酸的表达改变 脱羧酶（GAD）、N-甲基-D-天冬氨酸（NMDA）受体，或 慢性去传入状态下VNC中的钙视黄蛋白？ MCSDA的资助将使我能够熟练地使用 分子生物学技术和定量形态学研究， 人体组织标本，这是需要建立自己作为一个 学术神经学家，特别是在人类颞叶领域 骨和脑干病理学和神经化学

The long term goal of this proposal is to develop human models of deafferentation by studying the morphological and neurochemical changes secondary to specific lesions within the vestibular periphery. Two models are used in this study I: A lesion of Scarpa~s Ganglion and II: A lesion Affecting the Endorgans. A combination of classical histological techniques, immunohistochemistry, electron microscopy, molecular biologic techniques, and computer based quantitative analyses will be used to document the changes. One unique aspect of the present proposal is that a wide variety of human temporal bone and brain stem specimens are available for this study, including autopsy, archival and surgical specimens. This study will focus on specimens from patients in a chronic compensated state following a lesion of the vestibular periphery. Critical information regarding the following phenomenon in human vestibular periphery will be obtained: 1) Is there a dependency of the vestibular neuroepithelium on the vestibular nerve for survival? 2) Reciprocally, is the vestibular nerve dependent on the vestibular hair cells for survival? 3) Does retrograde degeneration occur in the presence of intact afferent dendrites? 4) Is there a subtype of calretinin immunoreactive Scarpa~s ganglion neuron which is resistant to retrograde degeneration? 5) Is there a qualitative correlation between the amount of degeneration in the endorgans and in Scarpa's ganglion? Within the vestibular nuclear complex (VNC), important data will be gathered on : 1) Does retrograde degeneration affect the central processes of the vestibular nerve after a lesion of the vestibular periphery? 2) Is there a permanent loss of synaptic density in the ipsilateral VNC after a lesion of Scarpa's ganglion and/or the endorgans? 3) is there an altered expression of glutamic acid decarboxylase (GAD), N-methyl-D-aspartate (NMDA) receptor, or calretinin in the VNC in Chronic deafferented states? The MCSDA grant will allow me to develop proficiency at using molecular biologic techniques and quantitative morphologic studies to human tissue specimens which is needed to establish myself as an academic neurotologist, specifically within the field of human temporal bone and brain stem pathology and neurochemistry