| Project/Area Number |
15K15524
|
|---|
| Research Category |
Grant-in-Aid for Challenging Exploratory Research
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Neurosurgery
|
|---|
| Research Institution | University of Yamanashi |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Renkei-kenkyūsha) |
HIRAYAMA Yuri 山梨大学, 総合研究部, 助教 (30732804)
KINOUCHI Hiroyuki 山梨大学, 総合研究部, 教授 (30241623)
|
|---|
| Research Collaborator |
SHINOZAKI Youichi
SHIGETOMI Eiji
|
|---|
| Project Period (FY) |
2015-04-01 – 2017-03-31
|
| Project Status |
Completed (Fiscal Year 2016)
|
| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Keywords | アストロサイト / 脳卒中 / 虚血耐性 / P2X7受容体 / HIF1a / グリア細胞 |
|---|
| Outline of Final Research Achievements |
A mild ischemic episode (preconditioning; PC) induces resistance to a subsequent severe ischemic injury in the brain. This phenomenon, known as ischemic tolerance, is an endogenous process that provides robust neuroprotection. So far there have already been a lot of research on ischemic tolerance, but almost all studies were performed from the point of view of neurons. We found that astrocytes are essential for the induction of ischemic tolerance, for which upregulation of P2X7 receptors is requireide. Here, as a downstream signal, we found that induction of HIF1a is essential HIF1a is well-know molecule that controls oxygen homeostasis, and increases in response to hypoxia/PHD2 in neurons. Here, we found that unlike neurons, astrocytes increased HIF1a in a hypoxia-independent manner but upregulated it in a P2X7 receptor-dependent fashion. Such astrocytic HIF1a is long-lasting, and allows astrocytes to produce ischemic tolerance.
|
