| Project/Area Number |
10671346
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KOBAYASHI Atsuki (2001) The Univ. of Tokyo, Dept of Orthop Surg, Instructor, 医学部・附属病院, 助手 (30333462)
荒井 勲 (2000) 東京大学, 医学部・附属病院, 助手 (10322760)
阿久根 徹 (1998-1999) 東京大学, 医学部・附属病院, 助手 (60282662)
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| Co-Investigator(Kenkyū-buntansha) |
OHNISHI Isao The Univ. of Tokyo, Dept of Orthop Surg, Assistant Prof, 医学部・附属病院, 講師 (70311628)
GOTO Takahiro The Univ. of Tokyo, Dept of Orthop Surg, Assistant Prof, 医学部・附属病院, 講師 (20272544)
TANAKA Sakae The Univ. of Tokyo, Dept of Orthop Surg, Instructor, 医学部・附属病院, 助手 (50282661)
NAKAMURA Kozo The Univ. of Tokyo, Dept of Orthop Surg, Prof, 医学部・附属病院, 教授 (60126133)
小林 篤樹 東京大学, 医学部・附属病院, 助手
荒井 勲 東京大学, 医学部・附属病院, 助手
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| Project Period (FY) |
1998 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Spinal cord injury / adenovirus / MEK I / 脊椎損傷 / シュワン細胞 / PI3キナーゼ / アデノウィルスベクター / MEK / PC12 / アポトーシス |
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| Research Abstract |
Spinal cord injury in adult mammals results in little axonal regeneration, although the mechanism of regeneration failure still remains elusive. Recent research has revealed that activation of the extracellular-signal-regulated kinases (ERKs) plays an important role in the neurite outgrowth. In the present study, we constructed a replication-defective adenovirus vector carrying mutated form of MEK1 (CA-MEK virus), which constitutively activate ERK pathway, and investigated its effect on thoracic spinal cord injury model in young adult rats as well as neurite outgrowth in vitro. In rat pheocromocytoma cell line PC12 cells, CA-MEK virus infection induced sustained activation of ERKs and stimulated neurite outgrowth in the absence of neurotrophic factors. In rat spinal cord transection model, injection of CA-MEK virus into the completely transected spinal cord efficiently activated ERKs in the supraspinal neurons and induced axonal regeneration across the transection site, which was confirmed by anterograde labeling with wheat-germ-agglutinin conjugated peroxidase (WGA-HRP). Spinal cord evoked potentials (SCEP) showed that these regenerated axons were electroconductive. Most importantly, CA-MEK virus-treated rats showed significant recovery of hind limb function 2 weeks after operation compared to the control rats treated with no virus or LacZ virus. These results suggest that adenovirus-mediated CA-MEK gene transduction offers a novel strategy for the gene therapy of spinal cord injury.
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