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

使用 PET 神经感受器成像和光学成像进行神经再生治疗的神经元传导实验分析。

• 批准号: 16390405
• 负责人: OHNO Kikuo
• 金额: $ 9.15万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390405/
• 关键词: neural transplantation; PET; dopaminergic neuron; neuroreceptor; optical imaging; neurogenerative therapy; Parkinson disease; substantia nigra; 再度医療

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

正电子发射断层扫描（PET）神经受体显像的实验性应用，现已被公认为是一种不可治愈的中枢神经系统疾病的新的治疗策略的发展的必然工具。在实验动物上使用光学成像也被认为是在已建立的电生理学方法和新开发的成像工具（如PET）之间进行调解的关键方法。我们使用PET和光学成像对脑疾病的动物模型进行了实验研究，以将其应用于神经再生新疗法的开发。主要研究内容包括：1）PET神经受体显像分析脑缺血和神经创伤引起的神经元损伤<11>。在我们以前的脑缺血急性期实验中，腺苷受体和腺苷受体的结合存在差异， ...更多信息 d苯二氮卓受体。然而，在慢性条件下，没有发现两个受体系统的结合之间的差异。我们还对慢性脑缺血性疾病患者进行了临床PET成像，观察到两种受体系统的偶联结合。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，而慢性期腺苷受体的结合反映了神经元系统的变化<11>。用于啮齿动物成像的微型PET系统用于该实验。我们成功地成像了撞击部位小胶质细胞的激活，这种激活在同一个体动物的随访中逐渐增加和减少。2）帕金森病动物模型的PET神经受体成像在本研究资助期间，我们的研究小组引入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损毁的帕金森病大鼠模型进行了胎黑质移植的显像实验。PET成像清楚地检测到神经植入后突触前和突触后多巴胺能功能的恢复。3）光学成像技术在啮齿动物脑片皮层-纹状体神经传导研究中的应用，建立了一个利用光学成像技术监测脑片皮层神经元刺激后纹状体神经元激活的实验系统。纳塔尔时啮齿动物的脑切片在高时空分辨率的记录系统上检测到从刺激部位到远端纹状体的信号传播。药物分别对多巴胺能系统或GABA能系统进行操作，可使传导减弱或增强。该系统可用于分析用于治疗帕金森病的体外植入神经组织的活力和连通性。少

项目成果

Overexpressed Skp2 within 5p amplification detected by array‐based comparative genomic hybridization is associated with poor prognosis of glioblastomas

• DOI: 10.1111/j.1349-7006.2005.00099.x
• 发表时间: 2005-10
• 期刊: Cancer Science
• 影响因子: 5.7
• 作者: K. Saigusa;N. Hashimoto;H. Tsuda;S. Yokoi;M. Maruno;T. Yoshimine;M. Aoyagi;Kikuo Ohno;I. Imoto;J. Inazawa

Correlation between quantitative imaging and behavior in unilaterally 6-OHDA-lesioned rats

• DOI: 10.1016/j.brainres.2005.09.055
• 发表时间: 2005-12-07
• 期刊: BRAIN RESEARCH
• 影响因子: 2.9
• 作者: Inaji, M;Okauchi, T;Suhara, T
• 通讯作者: Suhara, T

Severe haemodynamic stress in selected subtypes of patients with moyamoya disease: a positron emission tomography study

• DOI: 10.1136/jnnp.2003.025049
• 发表时间: 2005-05-01
• 期刊: JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
• 影响因子: 11
• 作者: Nariai, T;Matsushima, Y;Ohno, K
• 通讯作者: Ohno, K

Severe hemodynamic stress in selected subtypes of patients with moyamoya disease - A positron emission tomography study-.

烟雾病患者选定亚型的严重血流动力学应激 - 一项正电子发射断层扫描研究 -。

• 发表时间: 2005
• 期刊: Journal of Neurology Neurosurgery Psychiatry 76
• 作者: Nariai T;Matsushima Y;Imae S;Tanaka Y;Ishii K;Senda M;Ohno K
• 通讯作者: Ohno K

Aortic wall inflammation due to Takayasu arteritis imaged with 18F-FDG PET coregistered with enhanced CT.

• 发表时间: 2005-06
• 期刊: Journal of nuclear medicine : official publication, Society of Nuclear Medicine
• 作者: Yasushi Kobayashi;K. Ishii;K. Oda;T. Nariai;Youji Tanaka;K. Ishiwata;F. Numano