Behavioral and fMRI analysis of functional recovery in Parkinsonian animals

营养因子治疗为改善帕金森病多巴胺神经元的损伤和丢失提供了一种有希望的方法。 然而，为了使这种方法成功，需要开发安全有效的方法，将营养因子递送到大脑中，副作用最小。在这个项目中，我们测试的概念，使用可编程泵的控制，特定地点的营养因子的交付。 Medtronic泵用于检验GDNF的慢性脑内输注刺激黑质纹状体多巴胺系统的功能恢复的假设。 项目2有两个目标。 第一个是量化帕金森病特征的变化，伴随着慢性GDNF输注到侧脑室和壳核。 运动迟缓、僵硬、姿势、平衡和震颤将根据运动功能的标准化录像测试进行评级。 将使用自动运动评估小组量化粗动和精细运动时间。 第二个目标是利用功能性磁共振成像（fMRI），非侵入性地遵循黑质纹状体多巴胺系统的功能变化，表现出从慢性GDNF输注的行为恢复。 安非他明诱导的尾状核、壳核和黑质多巴胺能过程的刺激将通过功能磁共振成像在动物行为恢复过程中进行映射。

Trophic factor treatment offers a promising approach for ameliorating the injury and loss of dopamine neurons in Parkinson's disease. However, safe and efficacious methods for delivering trophic factors into the brain with minimal side effects need to be developed in order for this approach to be successful. In this project we test the concept of using programmable pumps for the controlled, site-specific delivery of trophic factors. Medtronic pumps are used to test the hypothesis that the chronic intracerebral infusion of GDNF stimulates functional recovery of the nigrostriatal dopamine system. Project 2 has two goals. The first is to quantify the changes in parkinsonian features accompanying chronic GDNF infusion into the lateral ventricle and the putamen. Bradykinesia, rigidity, posture, balance and tremor will be rated from standardized videotaped tests of movement functions. Coarse and fine motor movement times will be quantified using an automated Movement Assessment Panel. The second goal is to utilize functional magnetic resonance imaging (fMRI) to noninvasively follow functional changes in the nigrostriatal dopamine system in aminals showing behavioral recovery from chronic GDNF infusion. Amphetamine-induced stimulation of dopaminergic processes in the caudate nucleus, putamen and substantia nigra will be mapped by fMRI as animals undergo behavioral recovery.