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（SW）可以应用于多种治疗，如肾结石碎裂和药物输送系统。但是，在大脑中使用SW仍然具有挑战性，并且SW诱导的脑损伤阈值尚未确定。本研究的目的是阐明SW对大鼠脑的压力依赖性，评估其对胃癌细胞和人胶质瘤细胞的坏死和凋亡的影响，并在体外诱导药物进入细胞。8周龄雄性大鼠开颅后，在估计超压为1MPa和10MPa的条件下单次注射AgN_3产生的SW。采用苏木精-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（TUNEL）评价脑组织组织学变化。zad的效果。我们检测了非选择性caspase抑制剂FMK，以评估caspase依赖通路在sw诱导的脑损伤中的作用。此外，用gcity细胞和人胶质瘤细胞株对冲击波对抗癌药物的增强作用进行了评价。高压高压SW （10MPa）导致挫伤性出血，tunel阳性神经元显著增加，并在SW应用24小时后达到峰值，表现为染色质凝结、核分割和凋亡小体。低超压SW （1MPa）暴露后，神经元呈梭形变化，细胞核伸长，但未见明显损伤。反复给药zVAD。高压SW暴露24h后，FMK显著降低tunel阳性细胞数量（p<0.01）。双免疫荧光显示tunel阳性细胞仅在神经元内。在gcity细胞和胶质瘤细胞中均发现博来霉素对肿瘤细胞的增强作用，尤其是对肿瘤细胞的增强作用。推测sw致脑损伤阈值在1MPa以下，低于其他脏器。高压SW暴露（10MPa）可导致包括神经元凋亡在内的脑损伤，该损伤通过caspase依赖途径介导。这可能是在SW照射下抢救正常脑组织的治疗靶点。对于药物给药的探索，在临床应用前需要进一步的体内评价。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