2005 Fiscal Year Final Research Report Summary
Development of shock wave-induced drug delivery/gene induction system to deep brain lesion.
| Project/Area Number |
16390402
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Tohoku University |
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Principal Investigator |
TOMINAGA Teiji Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (00217548)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAYAMA Kazuyoshi Tohoku University, Biomedical Engineering Research Organization, Professor, 先進医工学研究機構, 教授 (40006193)
MYNHYON Sun Interdisciplinary Shock Waver Research Center, Institute of Fluid Science, Associate Professor, 流体科学研究所, 助教授 (00311556)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Medical Engineering / Laser Medicine / Minimally Invasive Surgery / Ho : YAG laser / Silver Azide / Rat / Apoptosis / Head Trauma |
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| Research Abstract |
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,
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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
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Research Products
(10 results)
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[Journal Article] Pulsed holmium : yttrium-aluminum-garnet laser-induced liquid jet as a novel dissection device in neuroendoscopic surgery.2004
Author(s)
Nakagawa A, Hirano T, Jokura H, Uenohara H, Ohki T, Hashimoto T, Menenges V, Sato Y, Kusaka Y, Ohyama H, Saito T, Takayama K, Shirane R, Tominaga T.
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Journal Title
J Neurosurg 101
Pages: 145-150
Description
「研究成果報告書概要(和文)」より
