1998 Fiscal Year Final Research Report Summary
Immuno-molecular-biological research on the pathogenesis of Theiler's murine encephalomyelitis virus-induced demyelinating disease.
| Project/Area Number |
09670649
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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 |
Neurology
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| Research Institution | Shinshu University |
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Principal Investigator |
INOUE Atsushi School of Medicine, Shinshu University Instructor, 医学部, 助手 (50213145)
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| Co-Investigator(Kenkyū-buntansha) |
CHANG Sung Koh School of Medicine, Shinshu University Associate Professor, 医学部, 助教授 (80143981)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Theiler's virus / demyelination / cytokine / Th1-Th2 balance / Blood brain barrier |
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| Research Abstract |
Intracerebral infection of susceptible mouse strains with Theiler's murine enephalomyelitis virus (TMEV) induces a chronic progressive demyelinating disease. This demyelinating disease (TMEV-IDD) is considered an infectious mouse model for MS because the disease displays similar histopathologic, genetic and clinical similarities to human MS.The breakdown of blood brain barrier is one of the important factors in the pathogenesis of demyelinating disease. We showed the fibrin deposition and increased permeability of blood brain barrier in the central nervous system correlated with the severity of TMEV-IDD (1). We examined the role of adhesion molecules of TMEV-IDD.We blocked the adhesion molecules such as ICAM-1 and LFA-1 by administration of these monoclonal antibodies (mAbs). These therapy suppressed the activity of virus specific CD4+ Th1 cells and clinical symptoms (2).
We also examined the role of Th1-Th2 balance in TMEV-IDD using anti-IL-12 mAb or drugs such as phosphatidylserine, pentoxifylline that have the suppressed of the development of this disease both clinically and histologically (3-5). In the demyelination, antibodies against viral antigens play important roles. We studied the B cell epitopes of TMEV viral capsid protein and the effect of antibodies against these epitopes (6). Taking together, our data elucidated the certain mechanism of viral demyelination and showed the possibility of novel therapeutic approach in the clinical treatment of demyelinating disease such as human multiple sclerosis.
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