Experimental use of positron emission tomography to analyze the damage of neuronal circuit and its restration with cell transplantation therapy.

我们建立了1)体内微PET研究，2)体外脑切片PET研究，3)临床人体PET研究相结合的实验体系，研究神经元移植等治疗性操作对神经元损伤的机制和功能再生的过程。几个研究课题的结果总结如下：1)利用动物PET相机研究帕金森病动物模型的多巴胺能功能。同时采用致死性黑质多巴胺能细胞植入治疗，PET观察各组功能恢复时间。这样的实验系统可以消除实验动物个体间的差异，效率很高。我们还可以建立一个实用的系统，使用微型pet相机，这是国内首次推出的，用于一般的实验使用。2)采用与上述相同的实验方案，我们发表了一篇论文，以…更多地比较实验动物的功能恢复程度与动物PET评估的多巴胺能神经元转导功能。这是首次报道在动物实验中对行为和受体功能进行定量比较。3)我们已经开始了PET实验来评估小胶质细胞在缺血和创伤后神经元损伤中的功能。本实验引入了一种合适的正电子标记放射配体来定位外周型苯二氮卓受体。定量测量动物缺血或创伤后的行为，并与动物PET相机测量的受体结合进行比较。4)我们开发了一种新的研究方法来可视化实验动物孵育脑片中的神经元传导。该系统采用荧光染料光学成像检测神经元活性，体外PET技术检测葡萄糖代谢。该系统也被用于分析从难治性癫痫患者身上切除的人脑病理。5)应用各种PET技术对缺血、肿瘤、癫痫、外伤等引起的脑损伤进行分析。将这些数据汇总进行统计分析，以调查功能损伤和治疗过程的恢复过程。该数据库可用于未来的研究，以评估新开发的再生疗法对人脑功能的恢复。少

We have established an experimental system with combined use of, 1) in vivo micro-PET study, 2) in vitro brain slice PET study, and 3) clinical human PET study to investigate the mechanism of neuronal damage and the process of functional regeneration by therapeutic maneuver such as neuronal transplantation. Results of several research topics has been summarized as below.1) We have investigated the dopaminergic function of animal model of Parkinson's disease using animal PET camera. We also treated these animals with the implantation of fatal nigral dopaminergic cells and followed the time course of functional recovery of each animals using PET. Such experimental system is highly efficient as we can eliminate the inter-individual variance of experimental animals. We could also establish a practical system of using micro-PET camera, that was introduced for the first time in our country, for general experimental use.2) Using the same experimental protocol as above, we published a paper to … More compare the degree of functional recovery of experimental animals with the function of dopaminergic neuronal transduction evaluated with animal PET. This is the first to report of quantitative comparison between behavior and receptor function in animal study.3) We have started an PET experiment to evaluate the function of microglia in relation to neuronal damage by ischemia and trauma. A suitable positron labeled radioligand to map the peripheral type benzodiazepine receptor was introduced for this experiment. Quantitative measurement of animal behavior after ischemia or trauma was performed to compare them with the receptor binding measured with animal PET camera.4) We have developed a novel research technique to visualize the neuronal conduction in incubated brain slices of experimental animal. Optical imaging with fluorescent dye to detect neuronal activity and the in-vitro PET technique to measure glucose metabolism was applied for this system. This system was also used for the analysis of pathology of human brain that was resected from patients with intractable epilepsy.5) We also applied various PET technique for the analysis of human brain damages elicited by ischemia, tumor, epilepsy or trauma etc. These data was pooled for statistical analysis to investigate the functional damage and the process of recovery by therapeutic procedures. Such database can be used for future study to evaluate the recovery of human brain function by newly developed regeneration therapy. Less