Development of shock wave-induced drug delivery/gene induction system to deep brain lesion.
开发冲击波诱导的药物输送/基因诱导系统以治疗深部脑损伤。
基本信息
- 批准号:16390402
- 负责人:
- 金额:$ 9.34万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (B)
- 财政年份:2004
- 资助国家:日本
- 起止时间:2004 至 2005
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
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
越来越多的证据表明,冲击波(SW)可应用于肾结石破碎和药物输送系统等多种治疗,但在大脑中使用冲击波仍然具有挑战性,并且冲击波引起的脑损伤的阈值尚未确定。本研究的目的是阐明SW对大鼠脑部的压力依赖性作用,评估坏死和凋亡的参与,并在体外诱导药物进入胃癌细胞和人胶质瘤细胞的细胞中。八周-老的开颅手术后,雄性大鼠在估计1MPa和10MPa的超压下暴露于AgN_3产生的单次SW,通过苏木精-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)评估大脑的组织学变化。检查非选择性半胱天冬酶抑制剂 zVAD 的作用以评估其贡献。此外,使用 GCIY 细胞和人神经胶质瘤细胞系评估了冲击波对半胱天冬酶依赖性脑损伤的影响。应用高超压 SW(10MPa)导致了与相关的挫伤性出血。 TUNEL 阳性神经元显着增加,在应用 SW 后 24 小时达到最大,表现出染色质浓缩、核分割和凋亡小体。低超压 SW (1MPa) 暴露导致神经元发生纺锤形变化和细胞核伸长,而没有明显的神经元损伤。高超压 SW 暴露后 24 小时,重复施用 FMK 显着减少了 TUNEL 阳性细胞的数量。 0.01)双重免疫荧光显示TUNEL阳性细胞仅存在于神经元中,尤其是博来霉素在GCIY中均被识别。推测SW引起的脑损伤阈值低于1MPa,低于其他器官的阈值。高超压SW暴露(10MPa)会导致脑损伤,包括神经元凋亡。 caspase依赖性途径可能是在SW暴露下拯救正常脑组织以治疗脑部疾病的治疗靶标,在临床应用之前需要进一步的体内评估。
项目成果
期刊论文数量(22)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Osteopromotion for cranioplasty using shock wave. Experiment using skull defect animal model.
使用冲击波进行颅骨成形术的骨质促进。
- DOI:
- 发表时间:2004
- 期刊:
- 影响因子:0
- 作者:Nakagawa A;Sato J;Hirano T;Ohki T;Saito T;Takayama K;Tominaga T.
- 通讯作者:Tominaga T.
Development of Ho : YAG laser-induced cavitational shock wave generator for endoscopic shock wave exposure.
开发用于内窥镜冲击波暴露的 Ho : YAG 激光诱导空化冲击波发生器。
- DOI:
- 发表时间:2004
- 期刊:
- 影响因子:0
- 作者:Sato J;Nakagawa A;Saito T;Hirano T;Ohki T;Uenohara H;Takayama K;Tominaga T.
- 通讯作者:Tominaga T.
Experimental application of pulsed Ho : YAG laser-induced cavitational shock wave generator as a novel drug delivery system.
脉冲Ho:YAG激光诱导空化冲击波发生器作为新型药物输送系统的实验应用。
- DOI:
- 发表时间:2006
- 期刊:
- 影响因子:0
- 作者:Ohki T;Nakagawa A;Sato J;Kambe M;Kato K;Hirano T;Uenohara H;Sun M;Tominaga T.Takayama K.
- 通讯作者:Tominaga T.Takayama K.
Experimental application of pulsed Ho : YAG laser- induced cavitational shock wave generator as a novel drug delivery system.
脉冲Ho:YAG激光诱导空化冲击波发生器作为新型药物输送系统的实验应用。
- DOI:
- 发表时间:2006
- 期刊:
- 影响因子:0
- 作者:Ohki T;Nakagawa A;Sato J;Kambe M;Kato K;Hirano T;Uenohara H;Sun M;Tominaga T;Takayama K.
- 通讯作者:Takayama K.
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TOMINAGA Teiji其他文献
重症呼吸不全に対するECMOの最新知見
ECMO治疗严重呼吸衰竭的最新研究结果
- DOI:
- 发表时间:
2022 - 期刊:
- 影响因子:0
- 作者:
SAITO Atsushi;INOUE Takashi;SUZUKI Shinsuke;EZURA Masayuki;UENOHARA Hiroshi;TOMINAGA Teiji;市場晋吾 - 通讯作者:
市場晋吾
脳神経外科医が手術で求めている画像‐術者は術前画像で何を見ているのか?‐
神经外科医生在手术期间寻求的图像 - 外科医生在术前图像中看到什么?
- DOI:
- 发表时间:
2021 - 期刊:
- 影响因子:0
- 作者:
FUJIMURA Miki;TOMINAGA Teiji;鰐渕昌彦 - 通讯作者:
鰐渕昌彦
Effectiveness of an actuator-driven pulsed water jet for removal of softened carious dentin
执行器驱动的脉冲水射流去除软化龋齿牙本质的有效性
- DOI:
10.4012/dmj.2021-234 - 发表时间:
2022 - 期刊:
- 影响因子:2.5
- 作者:
YOKOYAMA-SATO Yuka;NISHIOKA Takashi;NAGANUMA Yukihiro;TAKAHASHI Masatoshi;NAKAGAWA Atsuhiro;YODA Nobuhiro;SASAKI Keiichi;TAKAHASHI Nobuhiro;TOMINAGA Teiji;IIKUBO Masahiro - 通讯作者:
IIKUBO Masahiro
TOMINAGA Teiji的其他文献
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{{ truncateString('TOMINAGA Teiji', 18)}}的其他基金
Low overpressure shock wave for treatment in the deep brain
用于脑深部治疗的低超压冲击波
- 批准号:
26282116 - 财政年份:2014
- 资助金额:
$ 9.34万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Development of drug delivery system for central nervous system
中枢神经系统给药系统的开发
- 批准号:
21249077 - 财政年份:2009
- 资助金额:
$ 9.34万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Enhancement of drug induction into brain parenchyma using shock wave delivery system
使用冲击波传输系统增强药物诱导进入脑实质
- 批准号:
18390388 - 财政年份:2006
- 资助金额:
$ 9.34万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Nien9C oxiok in vasospasm folloroing experimenibl subamchnoid hemo rrhege
Nien9C Oxiok 在蛛网膜下腔出血后血管痉挛实验中的应用
- 批准号:
07671495 - 财政年份:1995
- 资助金额:
$ 9.34万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
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