| Project/Area Number |
10670717
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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 |
Pediatrics
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| Research Institution | Shinshu University School of Medicine |
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Principal Investigator |
MOTOKI Ichikawa Shinshu University, Dept. of Pediatrics, Assistant Prof., 医学部, 講師 (60223088)
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Atsushi Shinshu University, Dept. of Pediatrics, Associate, 医学部, 助手 (50213145)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Myelination / Demyelination / Myelin oligodendrocyte glycoprotein / Experimental autoimmune encephalomyelitis / IgGサブクラス / サイトカイン / ミエリンオリゴデンドロサイト糖蛋白 / ミエサンオリゴテンドロサイト糖蛋白 / I&Gサブクラス |
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| Research Abstract |
Myelination is observed in the human brain during the embryonic and neonatal periods and is important for the neurological development, however the mechanism of myelination remains to be determined. In the present study, we elucidated the immunological and hematological processes during the demyelination and remyelination in experimental autoimmune encephalomyelitis induced by myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 in NOD mice. Following immunization of MOG peptide 35-55, all NOD mice developed neurological disease with inflammation and demyelination in the central nervous system. The clinical severity of the disease was associated with serum IgG2b antibody titer against MOG peptide 35-55. When the animals were treated with anti-IL-12 antibody, significant suppression of the development and severity of the demyelinating disease was observed clinically and histologically. These results suggest that IgG2b antibody response and endogenous IL-12 are critically involved in the pathogenesis of MOG peptide induced demyelinating disease. We next demonstrated that plasma TAT values were increased just before the development of the symptoms, and decreased according to the improvement of the symptoms in experimental autoimmune encephalomyelitis. This result suggests that the coagulation-fibrinolysis system plays an important role for the pathogenesis of demyelination diseases. Further investigations of the autoimmune mediated demyelination pathways may not only provide important insights into the myelination of human central nervous system but also have distinct implications in the development of future successful therapies for neonatal neurological diseases such as periventricular leukomalacia.
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