| Project/Area Number |
16K10741
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurosurgery
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| Research Institution | Nihon University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
四條 克倫 日本大学, 医学部, 助教 (90800433)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000)
Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2016: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
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| Keywords | 脳挫傷 / マイクログリア / 炎症 / グリア / P2受容体 / アストロサイト / グリオトランスミッション |
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| Outline of Final Research Achievements |
The aim of this study was to investigate the effects of 5-BDBD a selective P2X4 receptor blocker and AZ11645373 a selective P2X7 receptor blocker against glial response in a rat cerebral contusion mode.
Following cerebral contusion, enormous number of activated microglia were found in the cortex and hippocampus. Administration of 5-BDBD, AZ11645373 or both significantly reduced the total number of microglia and the percentage of activated microglia. In a western blotting analysis, the expression of Iba-1 was reduced by administration of either 5-BDBD or AZ11645373 compare to the injury alone group. IL-1beta and IL-6 significantly increased after injury, but administration of either 5-BDBD, AZ11645373 or both decreased the amount of cytokine release.
The present study shows that inhibition of P2X4 and P2X7 receptor after cerebral contusion injury restricts the activation of microglia and reduce the release of some inflammatory cytokines.
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| Academic Significance and Societal Importance of the Research Achievements |
転落や転倒、交通事故による頭部外傷は常に発生し続けている疾患である。頭部外傷の中でも特に脳挫傷は現時点では有効な治療法がなく、不幸な転帰をたどることも多い。脳挫傷の治療対象は外傷後に引き起こされるさまざまな脳内の反応に限定される。これには炎症や血流の異常、脳浮腫、活性酸素の発生などがあげられる。本研究は脳挫傷後の炎症を引き起こすシグナル伝達系を遮断することにより、炎症反応を抑制しようとする研究である。今後頭部外傷の治療の一助になることを期待している。
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