Morphometric/immunocytochemical analysis of functional recovery in Parkinsonian

帕金森病功能恢复的形态测量/免疫细胞化学分析

• 批准号: 6353144
• 负责人: Don Marshall Gash
• 金额: $ 16.9万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6353144
• 关键词: Macaca mulatta; Parkinson's disease; autoradiography; brain mapping; central neural pathway /tract; disease /disorder model; dopamine; drug delivery systems; functional ability; histopathology; immunocytochemistry; in situ hybridization; nervous system regeneration; neuronal transport; neurotrophic factors

All three projects of this program focus on critically testing the central hypothesis that chronic infusions of GDNF promote the regeneration and functional recovery of the nigrostriatal dopamine system. Project 3 utilizes quantitative morphometric procedures, immunocytochemistry, in stu hybridization, immunoautoradiographic procedures and retrograde tract tracing to analyze the recovery of the nigrostriatal dopamine system in parkinsonian rhesus monkeys receiving GDNF. The effects of chronic infusions into two CNS sites are critically tested, the lateral ventricle and the putamen. The analysis includes determining the consequences of interrupting trophic factor for four months and then reinstating GDNF infusion for eight weeks. The results from these studies, combined with the neurochemical analyses in Project 1 and the behavioral and functional MRI measures of Project 2, should advance our understanding of the factors underlying successful regeneration in the parkinsonian brain. In addition, these studies significantly contribute to developing the methodology for chronically delivering other tropic factors and therapeutic compounds into the CNS.

该计划的所有三个项目都集中在批判性地测试GDNF的慢性输注促进黑质纹状体多巴胺系统的再生和功能恢复的中心假设。 项目3利用定量形态测量程序，免疫细胞化学，原位杂交，免疫放射自显影程序和逆行追踪来分析接受GDNF的帕金森病恒河猴黑质纹状体多巴胺系统的恢复。 慢性输注到两个中枢神经系统网站的影响进行了严格的测试，侧脑室和壳核。 该分析包括确定中断营养因子4个月，然后恢复GDNF输注8周的后果。 这些研究的结果，结合项目1中的神经化学分析和项目2中的行为和功能MRI测量，应该促进我们对帕金森病患者大脑成功再生的潜在因素的理解。 此外，这些研究显著有助于开发用于将其他热带因子和治疗性化合物长期递送到CNS中的方法。