| Project/Area Number |
22591590
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Cerebral neurosurgery
|
|---|
| Research Institution | Ehime University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
ONISHI Takanori 愛媛大学, 大学院・医学系研究科, 教授 (70233210)
KUMON Yoshiaki 愛媛大学, 大学院・医学系研究科, 准教授 (80127894)
JYU Penjan 愛媛大学, 大学院・医学系研究科, 助教 (40380216)
|
|---|
| Project Period (FY) |
2010 – 2012
|
| Project Status |
Completed (Fiscal Year 2012)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2012: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Keywords | 脳虚血 / 制御性T細胞 / FoxP3 / ヒスタミン / マイクログリア / 炎症 |
|---|
| Research Abstract |
The organic cation transporters 3 (= OCT3) was identified as an uptake-2 transporter, responsible for clearance of histamine. Because increasing evidence suggests the involvement of histamine in cerebral ischemia, we investigated the effects of targeted disruption of OCT3 on the severity of ischemic brain damage. Transient focal ischemia for 1 hour was induced by occlusion of the middle cerebral artery (MCA) of homozygous Oct3-deficient mice and their wild type littermates. Consequently, targeted disruption of OCT3 significantly increased histamine content in the ischemic cortex and significantly reduced the infarct volume after cerebral ischemia. Furthermore, this disruption prevented the reduction of regulatory T cell proportion after cerebral ischemia. Since repeated administration of L-histidine (a precursor of histamine) to wild-type mice also showed the same effects, our observations suggested that OCT3 is the molecule responsible for clearance of ischemia-induced histamine in the brain and targeted disruption of OCT3 ameliorated ischemic brain damage through an increase in regulatory T cells.
|
