Non-invasive measurement of cerebral inhibitory receptors and their neural circuit in epileptgenic

致癫痫脑抑制性受体及其神经回路的无创测量

基本信息

批准号：
12671343
负责人：
NARIAI Tadashi
金额：
$ 2.43万
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 (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671343/
关键词：
adenosine receptor benzodiazepine receptor positron emission tomography temporal lobe epilepsy hippocampus cerebral glucose metabolism C-11 MPDX kinic acid てんかん MEG 神経受容体ベンゾディアゼピンアデノシン

项目摘要

1) All the patients with intractable epilepsy who were operated on in Department of Neurosurgery, Tokyo Medical and Dental University underwent PET measurement of cerebral metabolic rate of glucose and the binding potential, of central benzodiazepine receptors. In 2001, a new project to image cerebral histamine receptor in epileptic foci with C-11 doxepine and PET was started. The results are ready to be analized with kinetic analysis of receptor binding.2) We have been developing a novel receptor ligand to map cerebral adenosine receptor system. Through this project, C-11 MPDX was recognized as a suitable ligand to image A1 receptor in vivo condition with PET. Pre-clinical research to establish the efficacy of this tracer was conducted with cat and monkey and enough data to indicate the usefulness and safetiness of this tracer was accumulated. Based on this data, PET imaging of adenosine A1 receptor in human brain will be started in next fiscal year.3) As described above, measurement of benzodiazepine and adenosine receptor system in human brain is and will be possible with PET. To confirm the contribution of these two receptor system in epileptogenicity, in vitro autoradiographical experiment was conducted with rats model of limbic seizure. Increased expressinon of these receptors was recognized in hippocampus of epilepsy rats.4) A method to investigate the cerebral metabolism and receptor binding using incubated living brain slice was developed using positron tracer. A new project to apply this technique to human brain specimen obtained from epilepsy patients was started.

1）东京医科齿科大学神经外科手术的所有难治性癫痫患者均进行PET脑葡萄糖代谢率及中枢苯二氮卓受体结合电位测定。 2001 年，启动了一个新项目，利用 C-11 多塞平和 PET 对癫痫病灶中的脑组胺受体进行成像。结果可以通过受体结合动力学分析进行分析。2）我们一直在开发一种新型受体配体来绘制脑腺苷受体系统图谱。通过该项目，C-11 MPDX 被认为是使用 PET 对 A1 受体体内条件进行成像的合适配体。为了确定该示踪剂功效的临床前研究是在猫和猴子身上进行的，并积累了足够的数据来表明该示踪剂的有用性和安全性。基于这些数据，人脑中腺苷A1受体的PET成像将于下一财年开始。3)如上所述，PET对人脑中苯二氮卓类和腺苷受体系统的测量现在和将来都是可能的。为了证实这两种受体系统在致癫痫性中的贡献，用边缘癫痫大鼠模型进行了体外放射自显影实验。在癫痫大鼠的海马中发现这些受体的表达增加。4)使用正电子示踪剂开发了一种利用孵育的活体脑切片研究脑代谢和受体结合的方法。一个将该技术应用于从癫痫患者身上获取的人脑样本的新项目已经启动。