Morphometric/immunocytochemical analysis of functional recovery in Parkinsonian

该计划的所有三个项目都专注于批判性地检验这一中心假设，即长期输注GDNF促进黑质纹状体多巴胺系统的再生和功能恢复。项目3利用定量形态计量学、免疫细胞化学、原位STU杂交、免疫放射自显影和逆行追踪等方法分析接受GDNF治疗的帕金森病恒河猴黑质纹状体多巴胺系统的恢复情况。对两个中枢神经系统部位，侧脑室和壳核的慢性输注的影响进行了严格的测试。这项分析包括确定中断营养因子四个月，然后恢复GDNF输注八周的后果。这些研究的结果，结合项目1中的神经化学分析和项目2中的行为和功能磁共振测量，应该会促进我们对帕金森病患者大脑成功再生的因素的理解。此外，这些研究还极大地促进了将其他热带因子和治疗化合物长期输送到中枢神经系统的方法学的发展。

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.