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

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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