| Project/Area Number |
26430066
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | Niigata University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
高橋 哲哉 新潟大学, 医歯学総合病院, 助教 (20515663)
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| Co-Investigator(Renkei-kenkyūsha) |
KANAZAWA Masato 新潟大学, 医歯学総合病院, 助教 (80645101)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 脳虚血 / プログラニュリン / 神経細胞保護 / 血管保護 / 抗炎症 / TDP43 / 脳梗塞 / 脳浮腫 / IL10 |
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| Outline of Final Research Achievements |
We observed that progranulin (PGRN) could protect against acute focal cerebral ischemia by variety of mechanisms, which we call "brain protection", including neuroprotection in part by inhibition of cytoplasmic redistribution of TDP-43 using PGRN knock-out mice, suppression of neuroinflammation via anti-inflammatory interleukin-10 in microglia, and attenuation of blood-brain barrier disruption via vascular endothelial growth factor. We also demonstrated the therapeutic potential of PGRN against acute focal cerebral ischemia using a rat autologous thromboembolic model with delayed tissue plasminogen activator treatment. Intravenously administered recombinant PGRN significantly reduced volumes of cerebral infarct and edema, suppressed hemorrhagic transformation, and improved motor outcome. PGRN may be a novel therapeutic target that provides brain protection such as vascular protection, anti-neuroinflammation, and neuroprotection.
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