Basic research to sonodynamic therapy for the brain tumor

在本研究中，我们研究了声动力处理是否会引起大鼠正常脑组织损伤，以及声动力处理对体外神经胶质瘤细胞的影响。在大鼠正常脑组织中，加或不加红曲（Rose bengal， RB）的超声聚焦照射均可引起局部破坏性病变，病变的发生与超声强度和照射时间成正比。病变是由空化效应和热效应引起的，因为有和没有RB照射的大脑温度没有差异。经Evans蓝色组织化学检查，RB组的病变比未RB组的大，提示声化学活性导致血脑屏障打开。用光敏剂（Photofrin，声动力处理）超声诱导C6大鼠胶质瘤细胞和2种人胶质瘤细胞系（U251和U105）凋亡，大鼠重组RAP能强烈抑制细胞凋亡。超声与光敏剂（Photofrin）对人胶质瘤细胞的作用取决于超声治疗的强度和持续时间。这些结果表明，如果选择适当的暴露参数，声动力治疗可以在大脑中使用，并且可能对胶质瘤的治疗有效。

In this study, we investigated whether or not the sonodynamic treatment might induced tissue damage in the rat normal brain, and the effect of sonodynamic treatment for glioma cells in vitro. In the normal brain tissue of rats, focused ultrasound irradiation with or without Rose bengal (RB) induced localized destructive lesions, and the occurrence of lesions was proportional to the intensity of the ultrasound and the irradiation time. The lesions were induced with a cavitation effect as well as a heat effect, because no difference was observed in the brain temperature between irradiation with and without RB.The lesions investigated by Evans blue histochemically became larger with RB than without RB suggesting an opening of the blood brain barrier due to sonochemical activity. Apoptosis was induced in C6 rat glioma cells, and two human glioma cell lines (U251 and U105) by ultrasound with photosensitizers (Photofrin, sonodynamic treatment), which was strongly inhibited by rat recombinant RAP.The effect of ultrasound with photosensitizers (Photofrin) in human glioma cells depended on the intensity and duration of the ultrasound treatment. These results indicated that a sonodynamic therapy can be used in the brain if the exposure parameters were selected properly, and it might be effective for the treatment of glioma.