| Project/Area Number |
16390405
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Cerebral neurosurgery
|
|---|
| Research Institution | Tokyo Medical and Dental University |
|---|
Principal Investigator |
OHNO Kikuo Tokyo Medical and Dental University, Graduate School, Professor, 大学院・医歯学総合研究科, 教授 (50014238)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
NARIAI Tadashi Tokyo Medical and Dental University, Medical Hospital, Lecturer, 医学部附属病院, 講師 (00228090)
SATO Katsushige Tokyo Medical and Dental University, Graduate School, Lecturer, 大学院・医歯学総合研究科, 講師 (80291342)
SUHARA Tetsuya National Institute of Radiological Sciences, Molecular Imaging Center, Group leader, 分子イメージング研究センター・分子神経イメージング研究グループ, グループリーダー (90216490)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2005: ¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 2004: ¥7,500,000 (Direct Cost: ¥7,500,000)
|
|---|
| Keywords | neural transplantation / PET / dopaminergic neuron / neuroreceptor / optical imaging / neurogenerative therapy / Parkinson disease / substantia nigra / 再度医療 |
|---|
| Research Abstract |
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-trauma
PET 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 Parkinsonism
In 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
|
