NEURAL AND PARANEURAL GRAFTS IN PARKINSONIANS MODELS

帕金森病模型中的神经和神经旁移植

• 批准号: 3100209
• 负责人: JOHN T HANSEN
• 金额: $ 72.03万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-02-01 至 1994-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3100209
• 关键词: Parkinson's disease; disease /disorder model; nervous system transplantation

Parkinson's disease is a relentlessly progressive neurodegenerative disorder afflicting over 500,000 Americans. Patients with parkinsonism can expect to live a normal lifespan due to levodopa and other drug therapies, but most experience a steadily eroding quality of life in the later stages of the disease. This program project was organized to (i) systematically investigative adrenal chromaffin cell transplantation as an approach to treating Parkinson's disease, and (ii) better understand the mechanisms underlying functional recovery from parkinsonism in rodent and nonhuman primate models of Parkinson's disease. The present program consists of three projects and two core facilities. In Project 1, Dr. Gash will critically test the hypothesis that increasing chromaffin cell survival in intrastriatal grafts significantly increases behavioral recovery in parkinsonian primates. In Project 2, Dr. Notter will characterize in depth the properties of primate Schwann cells and chromaffin cells by bioassays, immunoblasts and in situ hybridization for mRNA. She will also evaluate the response of primate chromaffin cells to factors they will be exposed to in implant sites including a aFGF, cytokines, macrophage-derived factors and levodopa. Dr. Hansen, in Project 3, using a selective lesion rat model will test the hypothesis that a host sprouting response is important for restoring striatal dopamine levels and may be the single most important event in ameliorating functional deficits that result from dopamine depletion in the striatum. Collectively, these studies should not only increase our understanding of the processes important for functional recovery from parkinsonism but should also be of significant benefit in designing new therapeutic approaches to the treatment of Parkinson's disease.

帕金森病是一种持续进行性神经退行性疾病 困扰超过 50 万美国人的疾病。 帕金森病患者可以 由于左旋多巴和其他药物治疗，预计能过上正常的寿命， 但大多数人在后期都会经历生活质量的稳步下降 的疾病。 该计划项目的组织目的是 (i) 系统地 研究性肾上腺嗜铬细胞移植作为一种方法 治疗帕金森病，以及 (ii) 更好地了解其机制 啮齿动物和非人类帕金森病的潜在功能恢复 帕金森病的灵长类动物模型。 目前的计划由三个项目和两个核心设施组成。 在 项目 1，Gash 博士将批判性地检验以下假设： 纹状体内移植物中嗜铬细胞的存活率显着增加 帕金森灵长类动物的行为恢复。 在项目 2 中，Notter 博士 将深入表征灵长类雪旺细胞的特性 通过生物测定、免疫母细胞和原位杂交来检测嗜铬细胞 mRNA。 她还将评估灵长类嗜铬细胞对 他们将在植入部位接触到的因素，包括 aFGF、 细胞因子、巨噬细胞衍生因子和左旋多巴。 汉森博士，在项目中 3、使用选择性病变大鼠模型将检验宿主的假设 发芽反应对于恢复纹状体多巴胺水平很重要 可能是改善功能缺陷的最重要的事件 这是由于纹状体中多巴胺消耗所致。 总的来说，这些研究不仅应该增加我们对 对于帕金森病功能恢复很重要的过程，但是 也应该对设计新的治疗方法有显着的益处 治疗帕金森病的方法。