| Project/Area Number |
15590466
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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 |
Applied pharmacology
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| Research Institution | Osaka University |
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Principal Investigator |
KOYAMA Yutaka Osaka Univ., Grad.Sch.of Pharmaceutical Sci., Associate Prof, 薬学研究科, 助教授 (00215435)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUDA Toshio Osaka Univ., Grad.Sch.of Pharmaceutical Sci., Prof., 薬学研究科, 教授 (00107103)
BABA Akemichi Osaka Univ., Grad.Sch.of Pharmaceutical Sci., Prof., 薬学研究科, 教授 (70107100)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | Glial cells / Astrocytes / Brain edema / Blood-Brain Barrier / Endothelial cells |
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| Research Abstract |
Increases in the permeability of In vitro Blood-Brain Barrier Model by Endothelns : An in vitro models of blood-brain barrier (BBB) using cultured astrocytes and brain capillary endothelial cells (bEnd.3) was made and the effects of endothelins on the permeability of this BBB model was examined. Endothelin-1 increased the permeability of bEnd.3 monolayer culture. RT-PCR analysis showed ETB receptors were expressed in bEnd.3 cells. These results suggest that endothelias are one of soluble factors inducing brain edema on brain pathologies and ETB receptor is a possible target of anti-brain edema drugs.
Production of Astrocyte-Derived Edema-Inducing Factors by Endothelins : Astrocyte is a component of BBB together with brain capillary endothelial cells and produces several soluble factors modulating BBB permeability. In cultured astrocytres, ET-1 increases mRNA levels of vascular endothelial cells growth factor (VEGF), monocyte chemoatractant protein -1 (MCP-1) and interleukin-8 (IL-8), which are shown to increases after brain pathologies and induces brain edema Matrixmetalloproteinase-2 and 9 (MMPs) degenerate extracellular matrix proteins, such as laminine and fibronectin, and are involved in angiogenesis after brain injuries. Endothelia-1 increased MMP-2 and 9 in cultured astrocytses. Administration of Ala-ET-1, a selective agonist for ETB receptors, increased expression of VEGF, IL-8, MMP-2 and MMP-9 in rat brain. These results suggest a possibility that endothelins cause brain edema through the production of these edema-inducing factors in astrocytes.
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