Functional alteration of glial cells and brain edema formation

内皮素增加体外血脑屏障模型的渗透性：使用培养的星形胶质细胞和脑毛细血管内皮细胞制备血脑屏障（BBB）的体外模型（bEnd.3），并检查内皮素对该BBB模型的渗透性的影响。内皮素-1增加bEnd.3单层培养物的渗透性。RT-PCR分析显示bEnd.3细胞表达ETB受体。这些结果提示，内皮细胞是脑病理过程中诱发脑水肿的可溶性因子之一，ETB受体可能是抗脑水肿药物的作用靶点。内皮素类物质对星形胶质细胞源性水肿诱导因子的产生：星形胶质细胞与脑毛细血管内皮细胞共同构成血脑屏障，并产生多种调节血脑屏障通透性的可溶性因子。在培养的星形细胞中，ET-1增加血管内皮细胞生长因子（VEGF）、单核细胞趋化蛋白-1（MCP-1）和白细胞介素-8（IL-8）的mRNA水平，其显示在脑病理后增加并诱导脑水肿基质金属蛋白酶-2和9（MMPs）降解细胞外基质蛋白，如层粘连蛋白和纤连蛋白，并参与脑损伤后的血管生成。内皮素-1增加培养星形胶质细胞中MMP-2和MMP-9的表达。给予ETB受体选择性激动剂Ala-ET-1可增加大鼠脑内VEGF、IL-8、MMP-2和MMP-9的表达。这些结果表明，内皮素通过在星形胶质细胞中产生这些水肿诱导因子而引起脑水肿的可能性。

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.