Development of drug delivery system for central nervous system disease using with temperature control devise

通过血脑屏障(BBB)的药物传递系统(DDS)有望提高癫痫和恶性脑肿瘤等神经系统疾病的药物疗效。为了开发DDS系统，分析了温度变化对分子BBB渗透性的控制。由小鼠内皮细胞制成的人工血脑屏障在15℃时暂时打开紧密连接。紧密连接的主要结构蛋白之一claudin5在15度时减少了表达。伊文斯蓝注射到一条大鼠的静脉上，当它冷却时，它泄漏到了大脑表面。通过温度控制，磁导率的增加是可逆的。在颞叶切除手术中，一位癫痫患者静脉注射吲哚青绿出现在脑表面的冷区。这些结果表明，温度控制可能以可逆的方式调制血脑屏障的渗透性。

Drug delivery system(DDS) through blood brain barrier(BBB) promises to enhance the effectiveness of medicine for nervous system diseases such as epilepsy and malignant brain tumors. In order to develop the DDS system, control of BBB permeability of molecules by alteration of temperature was analyzed. Tight junction of artificial BBB made from mouse endothelial cell was temporary opened at 15 degrees centigrade. And claudin5, one of the major structural proteins of the tight junction decreased the amount of expression at 15 degrees. Evans blue administered to a rat vein leaked to the brain surface when it was cooled. The increased permeability was reversible by the temperature control. Indocyanine green administered intravenously to an epilepsy patient appeared to the cooled area of brain surface at the surgery of temporal lobectomy. These results lead that the temperature control may modulate BBB permeability in a reversible fashion.