Morphometric/immunocytochemical analysis of functional recovery in Parkinsonian

该计划的所有三个项目都集中在批判性地测试慢性输注GDNF促进黑质纹状体多巴胺系统再生和功能恢复的中心假设。项目3利用定量形态学、免疫细胞化学、小鼠杂交、免疫自显影和逆行道示踪等方法分析接受GDNF的帕金森恒河猴黑质纹状体多巴胺系统的恢复情况。慢性输注到两个中枢神经系统部位，侧脑室和壳核的影响进行了严格的测试。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的神经化学分析和项目2的行为和功能MRI测量，应该促进我们对帕金森病大脑成功再生的因素的理解。此外，这些研究显著有助于开发慢性递送其他热带因子和治疗化合物到中枢神经系统的方法。

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.