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

我们建立了一个实验系统，结合使用，1）体内micro-PET研究，2）体外脑切片PET研究，3）临床人体PET研究，以研究神经元损伤的机制和功能再生的过程，通过治疗策略，如神经元移植。本课题的主要研究成果如下：1）利用动物PET成像技术研究了帕金森病动物模型的多巴胺能功能。我们还对这些动物植入了致命的黑质多巴胺能细胞，并使用PET跟踪每只动物的功能恢复时间。这种实验系统是高效的，因为我们可以消除实验动物的个体间差异。我们还可以建立一个实用的使用微型PET相机的系统，这是我国首次引入，用于一般实验用途。2）使用与上述相同的实验方案，我们发表了一篇论文， ...更多信息 比较实验动物的功能恢复程度与动物PET评价的多巴胺能神经元转导功能。这是第一次在动物研究中报告行为和受体功能之间的定量比较。3）我们已经开始了PET实验，以评估小胶质细胞在缺血和创伤引起的神经元损伤中的功能。本文介绍了一种适用于外周型苯二氮卓受体定位的正电子标记放射性配体。对缺血或创伤后的动物行为进行定量测量，以将其与动物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技术来可视化实验动物脑片孵育中的神经元传导。该系统采用荧光染料光学成像技术检测神经元活动，采用体外PET技术测量葡萄糖代谢。该系统还用于分析从难治性癫痫患者切除的人脑的病理。5）我们还应用各种PET技术来分析由缺血、肿瘤、癫痫或创伤等引起的人脑损伤。这些数据被合并用于统计分析，以研究功能损伤和治疗程序的恢复过程。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