Experimental analysis of neuronal conduction by neurogenerative treatment using PET neurorecepter imaging and optical imaging.

实验使用神经受体成像与正电子发射断层扫描（PET）现在被认为是一种不可避免的工具，为开发新的治疗手法，无法治愈的中枢神经疾病。在实验动物上使用光学成像也被认为是在成熟的电生理方法和新开发的成像工具（如PET）之间进行中介的关键方法。我们利用PET和光学成像技术对脑疾病动物模型进行了实验研究，并将其应用于神经再生新疗法的开发。进行了三大研究主题。1)完成猫脑缺血实验模型的PET神经受体显像分析脑缺血对神经元的损伤，并利用新研制的放射配体^<11>C-MPDX完成神经创伤性PET腺苷受体显像。在我们之前的脑缺血急性期实验中，腺苷受体与苯二氮卓受体的结合存在差异。然而，在慢性疾病中，两种受体系统的结合没有发现差异。我们还对慢性缺血性脑疾病患者进行了临床PET成像，观察到两种受体系统的耦合结合。上述结果提示，急性缺血期腺苷受体的结合反映了内源性腺苷系统对抗进行性缺血的变化，而慢性期的测量反映了神经元系统的成分。我们还利用新开发的^<11>C-DAA1106对大鼠液体撞击损伤模型进行了外周苯二氮卓受体的成像，该受体被认为是小胶质细胞激活的标志。本实验采用微型pet啮齿动物成像系统。我们成功地对撞击部位的小胶质细胞激活进行了成像，在同一只动物的随访中，小胶质细胞的激活逐渐增加和减少。2)帕金森病动物模型的PET神经受体成像在本课题资助期间，我们课题组引进了高分辨率啮齿动物PET相机（micro-PET）。利用该高分辨率PET系统，对OHDA损伤大鼠帕金森病模型进行胎儿神经移植成像实验。PET显像清楚地显示神经植入后突触前和突触后多巴胺能功能的恢复。该系统在临床前阶段已被证明是建立神经移植再生治疗的必然研究工具。3)利用光学成像技术分析鼠产后脑切片皮质纹状体神经传导。我们建立了一套实验系统，利用光学成像技术在出生后的啮齿动物脑切片上监测皮层神经元刺激后纹状体的神经元激活情况。在高时空分辨率记录系统上检测信号从受刺激部位向远端纹状体的传播。谷氨酸能系统或gaba能系统的药理作用分别减弱或增强了这种传导。该系统可用于分析体外植入神经组织的生存能力和连通性，用于治疗帕金森病。少

Experimental use of neuro-receptor imaging with positron emission tomography (PET) is now accepted as an inevitable tool for the development of new therapeutic maneuver of incurable central nervous disease. Use of optical imaging on experimental animal is also considered as a key method to mediate between the well established electrophysiological method and newly developed imaging tool such as PET. We have conducted experimental research on animal model of cerebral disorders using both PET and optical imaging to apply them for the development of novel therapy for neural regeneration. Three major research themes were conducted.1) PET neuroreceptor imaging to analyze neuronal damage by cerebral ischemia and neuro-traumaPET adenosine receptor imaging using newly developed radioligand, ^<11>C-MPDX, on cats experimental mode of cerebral ischemia was completed. In our former experiment on acute phase of cerebral ischemia, there existed discrepancy between the binding of adenosine receptor an … More d benzodiazepine receptor. However, in the chronic condition, no discrepancy was detected between the binding of two receptor systems. We also conducted a clinical PET imaging of patients with cerebral ischemic disease in chronic condition and observed a coupled binding of two receptor systems. These results suggested that the binding of adenosine receptor in the acute ischemic phase reflection the change of intrinsic adenosine system counteracting against progressive ischemia, but the measurement in chronic phase reflected the component in the neuronal system.We also performed an imaging of peripheral benzodiazepine receptor, which is considered as a marker of microglial activation, using newly developed ^<11>C-DAA1106 on rats fluid percussion injury model. The micro-PET system for rodent imaging was used for this experiment. We successfully imaged activation of microglia on the impact site, that was gradually increased and decreased on the follow-up of the same individual animal.2) PET neuroreceptor imaging in the animal model of ParkinsonismIn the period of the present research grant, high resolution animal PET camera for rodent (micro-PET) was introduced into our research group. Using this high resolution PET system, imaging experiment of fetal nigral transplantation on OHDA lesioned rats' model of Parkinson disease was conducted. PET imaging clearly detected the recovery of pre- and post-synaptic dopaminergic function by neural implantation. This system was proved to be an inevitable research tool for the establishment of regeneration therapy by neural transplantation in the stage of pre-clinical condition.3) Use of optical imaging in analyzing cortico-striatal neural conduction in the brain slice of post-natal rodent.We have established an experimental system to monitor the neuronal activation of striatum after the stimulation of cortical neuron using optical imaging technique on post-natal rodent brain slice. Spread of signal from the stimulated site to the remote striatum was detected on high time and space resolution recording system. The conduction was attenuated or enhanced by the pharmacological manipulation of glutamatergic or GABAergic system, respectively. This system can be utilized to analyze the viability and connectivity of extrinsically implanted neuronal tissue for the treatment of Parkinson disease. Less