| Project/Area Number |
14571373
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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 | Nagoya University |
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Principal Investigator |
MATSUYAMA Yukihiro Nagoya University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (20312316)
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| Co-Investigator(Kenkyū-buntansha) |
SAKAI Yoshihito Nagoya University, University Hospital, Medical Staff, 医学部附属病院, 医員
NAKAMURA Hiroshi Nagoya University, University Hospital, Medical Staff, 医学部附属病院, 医員
TSUJI Taichi Nagoya University, University Hospital, Medical Staff, 医学部附属病院, 医員
YOSHIHARA Hisatake Nagoya University, University Hospital, Medical Staff, 医学部附属病院, 医員
後藤 学 名古屋大学, 医学部附属病院, 医員
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | spinal cord injury / regeneration of spinal cord / Chondroitinase ABC / steroid / iNOS / ステロド |
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| Research Abstract |
The synthetic glucocorticosteroid methylprednisolone sodium succinate (MPSS) has been clinically used for the treatment of acute spinal cord injury (SCI) to promote the recovery of neurological functions. However, the mechanism of its beneficial actions is not entirely understood. Experimental evidence suggests that MPSS may contribute to some extent to neuroprotection in SCI. On the other hand, glial cell line derived neurotorophic factor (GDNF) acts as a potent survival factor for several neuronal populations, providing a therapeutic promise for neurological disorders. In this study, we have investigated the effect of MPSS on the production of GDNF mRNA and protein in the injured spinal cord tissues. Male Sprague-Dawley rats, 8 weeks old, were laminectomized at T9 and SCI was induced by dropping a weight of 10g. MPSS, 30mg/kg, was intravenously administrated to the rats after SCI and the animals were analyzed at the appropriate time points. The level of GDNF protein in the tissue was evaluated by immunohistochemistry and the mRNA levels were determined by RT-PCR. The GDNF mRNA expression and protein production were enhanced by SCI. The maximal values were obtained in the 12h after the injury. In MPSS treated group, however, the induction of GDNF mRNA was abolished and the increase of the GDNF protein production was diminished. The results indicated the MPSS repressed the GDNF gene expression and protein synthesis in the early stage after SCI. Considering the fact that MPSS diminishes the post traumatic inflammatory cascades accompanying edema and swelling to worsen the neuronal injury, the elevation of GDNF in the early stage of SCI might be disadvantageous to the survival and recovery of spinal neurons.
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