Development of shock wave-induced drug delivery/gene induction system to deep brain lesion.

越来越多的证据表明，冲击波可以应用于各种治疗，如肾结石粉碎和药物输送系统。但短波在脑内的应用仍具有挑战性，短波致脑损伤的阈值尚不确定。本研究的目的是阐明短波对大鼠脑的压力依赖性作用，探讨短波对胃癌细胞和人脑胶质瘤细胞的诱导作用，以及对肿瘤细胞的诱导作用。用苏木精-伊红染色和末端脱氧核苷酸转移酶介导的生物素化UTP缺口末端标记法(TUNEL)评价脑组织的变化。ZVAD的作用。检测非选择性caspase抑制剂FMK，以评价caspase依赖通路在短波致脑损伤中的作用。此外，…在GCIY细胞和人脑胶质瘤细胞系上观察了冲击波对抗癌药物的增强作用。高压(10 Mpa)照射导致挫伤出血，TUNEL阳性神经元显著增加，在照射后24小时达到最大，表现为染色质凝集、核分裂和凋亡小体。低超压(1 Mpa)暴露可引起神经元纺锤形改变和细胞核延长，但对神经元无明显损伤。重复使用zVAD。FMK在高压短波暴露后24小时显著减少TUNEL阳性细胞数(p&lt；0.01)。双重免疫荧光显示TUNEL阳性细胞仅见于神经元。GCIY细胞和人脑胶质瘤细胞均有抗肿瘤细胞的增强作用，尤其是博莱霉素。推测短波致脑损伤的阈值在1 Mpa以下，低于其他脏器。高压短波暴露(10 Mpa)可导致脑损伤，包括神经细胞凋亡，这是由caspase依赖的途径介导的。这可能成为在短波照射下抢救正常脑组织的治疗靶点。对于药物释放的探索，在临床应用之前有必要进行进一步的体内评价。较少

Increasing evidence suggests that shock waves (SW) can be applied for a variety of treatments such as renal stone fragmentation and drug delivery system. But the use of SW in the brain is still challenging, and the threshold of SW-induced brain injury is undetermined. The purpose of this study was to clarify the pressure dependent effect of SW on rat brain, and to evaluate the involvement of necrosis and apoptosis, and to induce drug into cell both in stomach cancer cell and in human glioma cell in vitro.Eight-week-old male rats were exposed to single shot of SW produced by AgN_3 under the estimated overpressure of 1MPa and 10MPa after craniotomy. Histological changes of the brain were evaluated by hematoxylin-eosin staining and terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL). The effect of zVAD. FMK, non-selective caspase inhibitor, was examined to evaluate the contribution of caspase-dependent pathway to SW-induced brain injury. In addition, … More enhancement of anticancer drug by shock wave were evaluated using GCIY cell and human glioma cell line.Application of high-overpressure SW (10MPa) resulted in a contusional hemorrhage associated with a significant increase in TUNEL-positive neurons, which were maximized at 24 hours after SW application, exhibiting chromatin condensation, nuclear segmentation, and apoptotic bodies. Low-overpressure SW (1MPa) exposure resulted in spindle-shaped changes of neurons and elongation of nucleus without marked neuronal injury. Repeated administration of zVAD. FMK significantly reduced the number of TUNEL-positive cells 24hours after high-overpressure SW exposure (p<0.01). Double immunofluorescence showed that TUNEL-positive cells were exclusively in neuron. Enhancement of anticancer cell, especially bleomycin were recognized both in GCIY cell and human glioma cell. The threshold of SW-induced brain injury is speculated to be under 1MPa, which is lower than that in other organs. High-overpressure SW exposure (10MPa) results in brain injury including neuronal apoptosis, which is mediated by caspase-dependent pathway. This could be the therapeutic target for rescuing normal brain tissue under SW exposure for brain disorders. For drug delivery exploration, further evaluation in vivo is necessary before clinical application. Less