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丧失提供了一种有希望的方法。然而，为了使这种方法取得成功，需要开发安全有效的方法，以最小的副作用将营养因子输送到大脑中。在这个项目中，我们测试了使用可编程泵来控制特定地点的营养因子输送的概念。使用美敦力泵来验证慢性脑内灌注GDNF刺激黑质纹状体多巴胺系统功能恢复的假设。项目2有两个目标。首先是量化伴随侧脑室和壳核慢性GDNF输注的帕金森特征的变化。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分。粗大和精细的运动时间将使用自动运动评估小组进行量化。第二个目标是利用功能性磁共振成像（fMRI）无创跟踪显示慢性GDNF输注后行为恢复的动物黑质纹状体多巴胺系统的功能变化。在动物行为恢复过程中，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fMRI绘制。

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.