HUMAN MODEL OF VESTIBULAR DEAFFERENTATION

这项提议的长期目标是开发人类模型 去传入的形态和神经化学研究 继发于前庭周围特定病变的改变。 本研究采用两种模型：SCARPA~S神经节损毁模型 II：影响内脏的病变。古典与古典的结合 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 将使用分析来记录这些更改。有一个独特的方面 目前的建议是各种各样的人类颞骨 和脑干标本可用于这项研究，包括 尸检、档案和手术标本。这项研究将集中在 来自慢性代偿状态的患者的样本 前庭周围的病变。 关于人类以下现象的关键信息 将获得前庭周围：1)是否存在依赖关系 前庭神经上的前庭神经上皮细胞生存？2) 反过来，前庭神经依赖于前庭毛发吗？ 为了生存的细胞？3)退行性变是否发生在 是否存在完整的传入树突？4)是否存在亚型 Calretinin免疫反应抗SCARPA~S神经节神经元 与退行性变有关？5)是否存在质的相关性 在内脏和斯卡帕的退化量之间 神经节？ 在前庭核复合体(VNC)内，重要数据将是 总结如下：1)退行性变是否影响中枢 前庭损伤后前庭神经的突起 外周有无突触密度的永久性丧失？ Scarpa‘s神经节和/或损伤后同侧VNC 内脏？3)谷氨酸的表达有变化吗？ 脱羧酶(GAD)、N-甲基-D-天冬氨酸(NMDA)受体或 Calretinin在慢性去传入状态VNC中的作用？ 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研究 需要人体组织样本来证明我是一个 学术神经病学家，特别是在人类颞叶领域 骨和脑干病理与神经化学

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