| Project/Area Number |
18K10706
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 59010:Rehabilitation science-related
|
|---|
| Research Institution | Nagoya University |
|---|
Principal Investigator |
Lee Sachiko 名古屋大学, 医学系研究科(保健), 准教授 (80599316)
|
|---|
| Project Period (FY) |
2018-04-01 – 2023-03-31
|
| Project Status |
Completed (Fiscal Year 2022)
|
| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Keywords | 痙縮 / 脳梗塞 / 可塑的変化 / 恒常的可塑的変化 / MdV / MRI / マンガン造影MRI / 恒常性シナプス可塑性 / 恒常的シナプス可塑性 / 脳活動 / 恒常的可塑性 |
|---|
| Outline of Final Research Achievements |
The spasticity develops after a certain period following stroke. We examined to confirm brain regions associated with spasticity using activation induced manganese-enhanced MRI. We found that neuronal activity at contralesional medullary reticular formation ventral part (MdV) in 1 week stroke mice was significantly upregulated compared with sham. Although the neuronal activity in MdV was showed significantly lower by electric stimulation of ipsi-afferent nerve, however, the inhibition of neuronal activity in 2 or 4 weeks after stroke did not confirm. Next, we confirmed whether the mechanisms of homeostatic plasticity after stroke show at contralesional MdV. We checked to change of subunits expression of AMPA receptors. We found GluA1 subunit density increased in stroke from 3 to 7 days, and with a shift toward increased GluA2 density at 14 days. This switch has previously been observed and the expression of GluA2-lacking AMPAR is needed for the induction of homeostatic plasticity.
|
| Academic Significance and Societal Importance of the Research Achievements |
痙縮発症メカニズム研究は脊髄レベルでの解析であり、脊髄より上位の脳領域における研究は行われていない。本研究で初めて痙縮発症脳梗塞マウスにおける脳幹網様体MdV領域における一過性の脳活動の高まりと、末梢神経からの電気刺激によるMdVの活動抑制が痙縮発症後2~4週間時点で消失していることが明らかになった。また脳梗塞後1週間のMdV神経活動の高まりには、恒常的可塑的変化が関連していることが明らかになった。
痙縮治療は脊髄運動神経細胞の活動抑制を中心とする対処療法しかない。さらにその治療は慢性化した時点で実施される。発症メカニズムの一端の解明から、次の治療戦略への開発につながると考える。
|
