Establishment of in vitro screenin models for new drugs against brain edema

1）细胞毒性水肿的体外模型：L-谷氨酸诱导的培养星形胶质细胞肿胀表现出两种成分。Quisqualate诱导快速组分，而threo-hydroxy-aspartate诱导延迟组分。这些结果表明，快速肿胀是由L-谷氨酸受体激活引起的，延迟肿胀是由转运体激活引起的。星形胶质细胞释放牛磺酸。因此，作为星形胶质细胞的功能变化，检查了L-谷氨酸及其类似物对牛磺酸释放的影响。所有诱导星形胶质细胞肿胀的L-谷氨酸类似物均刺激培养星形胶质细胞释放牛磺酸。红藻氨酸盐释放牛磺酸而不肿胀。这些结果表明，这是两种机制，在L-谷氨酸诱导的星形胶质细胞牛磺酸释放。这将发表在即将出版的《神经科学研究杂志》上。2）血脑屏障的体外模型：我们表明内皮素调节培养的星形胶质细胞的形态分化（Brain Res.，600）。伴随着形态学的改变，星形胶质细胞的细胞骨架肌动蛋白也发生了重组。提示内皮素是血脑屏障形成的重要因素。这将发表在即将出版的《神经科学》一书中。内皮细胞的肌动蛋白重组是血管通透性的基础。内皮素对细胞松弛素B诱导的牛脑内皮细胞肌动蛋白重组无影响。

1)In vitro model of cytotoxic edema : L-Glutamate-induced swelling of cultured astrocytes showed two components. Quisqualate induced the rapid component, while threo-hydroxy-aspartate did the delayd one. These results suggest that the rapid swelling was caused by activation of L-glutamate receptors and the delayd one was by that of transporters. Swollen astrocytes release taurine. Thus, as a functional change of astrocytes, effects of L-glutamate and its analogues on taurine release were examined. All of L-glutamate analogues to induce astrocytic swelling stimulated taurine release from cultured astrocytes. Kainate released taurine without swelling. These results indicate that these are two mechanisms in L-glutamate-induced astrocytic taurine release. This will be published in a coming volume of "J.Neurosci.Res.".2)In vitro model for blood-brain barrier : We showed that endothelins modulate morphological differentiation of cultured astrocytes (Brain Res., 600). And accompanying with the morphological changes, astrocytic cytoskeletal actin is re-organized. These results suggest that endothelins are important factors to make blood-brain barrier tight. This will be published in a coming volume of "Neuroscience". Actin re-organization of endothelial cells underlies permeability of blood vessels. Endothelins had no effects on cytochalasin B-induced actin re-organization of endothelial cells from bovine brain.