| Project/Area Number |
22591584
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Mie University |
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Principal Investigator |
SUZUKI Hidenori 三重大学, 大学院・医学系研究科, 教授 (90345976)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 脳血管障害学 / くも膜下出血 / 脳損傷 / 細胞外基質蛋白 / 脳血管攣縮 / 細胞外基質 / オステオポンチン / マトリックス細胞蛋白 / 血液脳関門障害 / 脳浮腫 / ラット / siRNA |
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| Research Abstract |
Subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) potentially contributes to poor outcome, one of whose key pathologic manifestation is the breakdown of the blood-brain barrier (BBB). We determined the role of osteopontin (OPN), a pleiotropic extracellular matrix glycoprotein (matricellular protein [MCP]), in the post-SAH BBB disruption in rats. The OPN levels in the brain were significantly induced and peaked at 72 hours after SAH, in the recovery phase of EBI. OPN siRNA significantly blocked the endogenous OPN induction and aggravated neurological impairment and BBB disruption at 72 hours after SAH. Pre-SAH administration of recombinant OPN (r-OPN)significantly prevented a loss in body weight, neurological impairment, brain edema and BBB disruption compared with the control rats. Treatment with r-OPN was associated with the deactivation of NF-κB activity, inhibition of MMP-9 induction, and the consequent preservation of cerebral microvessel basal lamina proteins and tight junction proteins.These findings suggest the protective effects of OPN against BBB disruption after SAH.In addition, we obtained new findings, suggesting that tenascin-C, another MCP, causes brain injury after SAH.
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