Project/Area Number |
18K16554
|
Research Category |
Grant-in-Aid for Early-Career Scientists
|
Allocation Type | Multi-year Fund |
Review Section |
Basic Section 56010:Neurosurgery-related
|
Research Institution | Kanazawa University |
Principal Investigator |
|
Project Period (FY) |
2018-04-01 – 2021-03-31
|
Project Status |
Completed (Fiscal Year 2020)
|
Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | early brain injury / subarachnoid hemorrhage / endoplasmic reticulum / 小胞体ストレス応答 / くも膜下出血後早期脳損傷 / くも膜下出血 / 早期脳損傷 |
Outline of Final Research Achievements |
Subarachnoid hemorrhage model was created in wild-type mice and ATF6 knockout mice and compared, no clear difference in neurological findings was found 24 hours after model creation. In addition, the brain was taken out and the degree of cerebral edema calculated water content ratio was compared, however no clear difference was observed here either. Comparing how the endoplasmic reticulum stress response occurs in the subarachnoid hemorrhage group and the sham group, the expression of ATF6, which is the main transcription factor of the endoplasmic reticulum stress response, is higher in the subarachnoid hemorrhage group than in the sham group. It was significantly abundant, and the downstream molecular chaperones GRP78 and CHOP were also highly expressed, confirming that the endoplasmic reticulum stress response was induced.
|
Academic Significance and Societal Importance of the Research Achievements |
マウスをくも膜下出血群としたものでは小胞体ストレス応答の主幹転写因子であるATF6の発現がsham群より有意に多くみられ、下流の分子シャペロンのGRP78やCHOPも多く発現しており、小胞体ストレス応答が誘導されていることが確認された。小胞体ストレス応答の制御はくも膜下出血後の病態解明のターゲットとなりうる。 しかし、くも膜下出血モデルを野生型マウスとATF6ノックアウトマウスにて作成し、比較すると、24時間後の時点で神経学的所見や脳浮腫の程度に差異はなく、小胞体ストレス応答が及ぼす影響については検討の余地が残っている。
|