| Project/Area Number |
10671332
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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 | KINKI UNIVERSITY |
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Principal Investigator |
KATAOKA Kazuo Kinki University, Dept. Neurosurgery, Associate Prof., 医学部, 助教授 (10221178)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUO Osamu Kinki University, Dept. Physiology, Prof., 医学部, 教授 (40030879)
TANEDA Mamoru Kinki University, Dept. Neurosurgery, Prof., 医学部, 教授 (10236713)
ASAI Toshiharu Kinki University, Dept. Neurosurgery, Associate Prof., 医学部, 講師 (20248008)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1998: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Plasminogen activator / Brain injury / Angiogenesis / Brain edema / 脳浮腫 / ミクログリア / 神経外傷 / uPA / tPA |
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| Research Abstract |
Urokinase type plasminogen activator (uPA) involves tissue fibrinolysis that is related to the healing process, development, and tumor invasion. Plasminogen inhibitor-1 (PAI-1) inhibits the protelytic activity of uPA and may enhance the brain vasculature after brain injury. We studied brain edema and changes in the vasculature after a brain stab wound in uPA-deficient, uPA receptor-deficient, and PAI-1-deficient mice, and control mice. Compared to control mice, the extravasation of immunoglobulin was significantly greater in PAI 1 deficient mice at 3 days after the lesion was placed, less pronounced in uPA-deficient mice and similar to the controls in uPA receptor-deficient mice. Von Willebrand factor-positive vascular structures increased in number 8 days after lesioning in PAI-1 deficient mice. Furthermore, irregular and proliferative collagen Type IV-positive microvasculatures were observed in all PAI-1-deficient mice and in 20% of control mice 8 days after lesion placement. Those findings are indicative of increased angiogenesis. Our study clearly shows that uPA contributes to the development of secondary brain damage due to a breakdown of microvascular extracellular matrix protein, and that uPA plays a role without binding to its receptor in the acute stage. PAI-1 inhibits traumatic brain edema. On the other hand, plasminogen activator facilitates angiogenesis necessary for healing after brain injury.
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