Effects of novel brain prothctants on neuroregeneration falbwing brain ischemia
Project/Area Number |
18590958
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Neurology
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Research Institution | Nippon Medical School |
Principal Investigator |
KATAYAMA Yasuo Nippon Medical School, Graduate School of Medicine, Professor (70152692)
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Co-Investigator(Kenkyū-buntansha) |
神谷 達司 岡山大学, 大学院歯薬学総合研究科, 助教授 (70233955)
|
Project Period (FY) |
2006 – 2007
|
Project Status |
Completed (Fiscal Year 2007)
|
Budget Amount *help |
¥3,660,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥360,000)
Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
|
Keywords | brain ischemia / brain nrotection / neuroregeneration / bone marrow cell / 脳保護薬 / 神経成長因子 / 遺伝子導入 |
Research Abstract |
Objects and Methods : Neuroregeneration and releasing neurotraphic factors have been considered as a mechanism for functional improvement after transplantation of bone marrow cells in experimental brain ischemia model. However protective effects of transplantation of bone marrow cells immediately after reperfusion have been rarely investigated. The present study examined, using rat transient focal ischemia model (90 min), different protective effects between intra-arterial and intravenous administration routs after transplantation of bone marrow mononuclear cells (BMMCs), which need no incubation period. Then, the present study sought to investigate whether an intravenous transplantation of bone marrow stromal cells (BMSCs), which require incubation period, has also protective effects in the same rat model, and whether a combined therapy with BMSC transplantation and immunosuppressant FK506 enhance such neuroprotection. Furthermore, distribution and differentiation of the transplanted
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BMSCs was also investigated, and longitudinal cellular dynamics of the transplanted cells using MRI. Results : Intra-arterial BMMC transplantation ameliorated infarct volume and improved functional scores, while intravenous BMMC transplantation had no such protective effects. The transplanted BMMCs were observed more frequently within the ischemic hemisphere in the intra-arterial administration group than the intravenous administration group. A combined therapy with intravenous BMSC transplantation and FK506 showed greater neuroprotection. The transplanted BMSCs were differentiated into neurons and astrocytes by one month after transplantation. MRI study revealed that the transplanted cells labeled with superparamagnetic iron oxide were observed on T2 weighted images, and that such cells were gradually decreased in number by one month after transplantation. Conclusions: The present study clearly showed that intra-arterial administration immediately after reperfusion potentiated the effective delivery of BMMCs to the brain compared to intravenous administration, and that FK506 combined with BMSC transplantation enhanced such neuroprotection, leading to a decrease in ischemic damage and good functional recovery in rat transient ischemia model. Efficient BMMC delivery to the brain and modification of transplantation circumstance may be important in clinical application of BMMC transplantation for the treatment of acute ischemic stroke. Less
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Report
(3 results)
Research Products
(14 results)
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[Presentation] MRI monitoring of transplanted autologous bone marrow mononuclear cells in rat brain ischemia model2008
Author(s)
Kamiya, N., Ueda, M., Igarashi, H., Suda, S., Nishiyama, Y., Katayama, Y
Organizer
The 33rd Annual Meeting of Japanese Society for Stroke
Place of Presentation
Kyoto, Japan
Year and Date
2008-03-20
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Treatment using bone marrow stromal cells in rat brain ischemia model : neuroregeneration and neuroprotective effect2007
Author(s)
Suda, S., Shimazaki, K., Ueda, M., Kato, K., Inaba, T., Kamiya, N., Nishiyama, Y., Okubo, S., Yokota, H., Oguro, K., Watanabe, H., Katayama, Y
Organizer
The 30th Annual Meeting of Japanese Society for Molecular Biology
Place of Presentation
Yokohama, Japan
Year and Date
2007-12-14
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Different effects of brain protection between administration routes of bone marrow mononuclear cells in rat brain ischemia model2007
Author(s)
Kamiya, N., Ueda, M., Igarashi, H., Suda, S., Nishiyama, Y., Katayama, Y
Organizer
The 19th Annual Meeting of Japanese Society for Cerebral Blood Flow and Metabolism
Place of Presentation
Morioka, Japan
Year and Date
2007-10-25
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Intra-arterial transplantation of bone marrow mononuclear cells immediately after reperfusion ameliorates brain injury following transient focal ischemia in rats2007
Author(s)
Kamiya, N., Igarashi, H., Nishiyama, Y., Ueda, M., Suda, S., Katayama, Y
Organizer
The 23rd International Symposium on Cerebral Blood Flow, Metabolism and Function
Place of Presentation
Osaka, Japan
Year and Date
2007-05-22
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Effect of early administration of autologous bone marrow mononuclear cells on brain protection in rat brain ischemia model2007
Author(s)
Kamiya, N., Igarashi, H., Nishiyama, Y., Ueda, M., Suda, S., Katayama, Y
Organizer
The 48th Annual Meeting of Japanese Society for Neurology
Place of Presentation
Nagoya, Japan
Year and Date
2007-05-17
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Effect of immediate transplantation of autologous bone marrow mononuclear cells on brain protection in rat focal brain ischemia model2007
Author(s)
Kamiya, N., Igarashi, H., Nishiyama, Y., Ueda, M., Suda, S., Katayama, Y
Organizer
The 32nd Annual Meeting of Japanese Society for Stroke
Place of Presentation
Fukuoka, Japan
Year and Date
2007-03-23
Description
「研究成果報告書概要(欧文)」より
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