Anti-inflammatory therapy by ibudilast, a phosphodiesterase inhibitor, in demyelination of twitcher, a genetic demyelination model
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Kagitani Shimono, Kuriko, et al. Anti-inflammatory Therapy by Ibudilast, a Phosphodiesterase Inhibitor, In Demyelination of Twitcher, a Genetic Demyelination Model. BioMed Central Ltd, 2005. https://doi.org/10.17615/51z3-w453APA
Kagitani Shimono, K., Mohri, I., Fujitani, Y., Suzuki, K., Ozono, K., Urade, Y., & Taniike, M. (2005). Anti-inflammatory therapy by ibudilast, a phosphodiesterase inhibitor, in demyelination of twitcher, a genetic demyelination model. BioMed Central Ltd. https://doi.org/10.17615/51z3-w453Chicago
Kagitani Shimono, Kuriko, Ikuko Mohri, Yasushi Fujitani, Kinuko Suzuki, Keiichi Ozono, Yoshihiro Urade, and Masako Taniike. 2005. Anti-Inflammatory Therapy by Ibudilast, a Phosphodiesterase Inhibitor, In Demyelination of Twitcher, a Genetic Demyelination Model. BioMed Central Ltd. https://doi.org/10.17615/51z3-w453- Creator
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Kagitani-Shimono, Kuriko
- Affiliation: School of Medicine, Department of Pathology and Laboratory Medicine
- Other Affiliation: Department of Developmental Medicine (Pediatrics), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565- 0871, Japan; Department of Molecular Behavioral Biology, Osaka Bioscience Institute, 6-2-4, Furuedai, Suita, Osaka, 565-0874, Japan
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Mohri, Ikuko
- Other Affiliation: Department of Developmental Medicine (Pediatrics), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565- 0871, Japan; Department of Molecular Behavioral Biology, Osaka Bioscience Institute, 6-2-4, Furuedai, Suita, Osaka, 565-0874, Japan
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Fujitani, Yasushi
- Other Affiliation: Department of Molecular Behavioral Biology, Osaka Bioscience Institute, 6-2-4, Furuedai, Suita, Osaka, 565-0874, Japan
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Suzuki, Kinuko
- Affiliation: School of Medicine, Department of Pathology and Laboratory Medicine
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Ozono, Keiichi
- Other Affiliation: Department of Developmental Medicine (Pediatrics), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565- 0871, Japan
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Urade, Yoshihiro
- Other Affiliation: Department of Molecular Behavioral Biology, Osaka Bioscience Institute, 6-2-4, Furuedai, Suita, Osaka, 565-0874, Japan
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Taniike, Masako
- Other Affiliation: Department of Developmental Medicine (Pediatrics), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565- 0871, Japan
- Abstract
- Abstract: Background: Twitcher mouse (twi/twi) is an authentic murine model of Krabbe's disease. Accumulation of psychosine, resulting in apoptosis of oligodendrocytes and subsequent demyelination, is a cardinal event to the pathogenesis of this disease. Moreover, recruitment of inflammatory cells plays a significant role in the pathological process in the twi/twi central and peripheral nervous systems. In this study, we investigated the 1) the relationship between tumor necrosis factor-α (TNFα), pro-inflammatory cytokine, and the progression of this disease and 2) effect of the anti-inflammatory therapy by ibudilast, a phosphodiesterase inhibitor. Methods: We quantified the expression level of TNFα and TNF-receptor mRNA in twi/twi using semi-quantitative RT-PCR. The relationship between TNFα expression, apoptosis of oligodendrocytes and demyelination was studied with immunohistochemistry and TUNEL method. We then treated twi/twi with a daily intraperitoneal injection of ibudilast (10 mg/kg), which suppress TNFα production in the brain. Results: We found that TNFα-immunoreactive microglia/macrophages appeared in the twi/twi brain and that the mRNA levels of TNFα and TNF-receptor 1 was increased with the progression of demyelination. The distribution profile of TNFα-immunoreactive microglia/macrophages overlapped that of TUNEL-positive oligodendrocytes in the twi/twi brain. When twi/twi was treated with ibudilast from PND30, the number of oligodendrocytes undergoing apoptosis was markedly reduced and demyelination was milder. Obvious improvement of clinical symptom was noted in two of five. The failure of constant clinical improvement by ibudilast may result from hepatotoxicity and/or the inhibition of proliferation of NG2-positive oligodendrocyte precursors. Conclusion: We conclude that anti-inflammatory therapy by a phosphodiesterase inhibitor can be considered as a novel alternative therapy for Krabbe's disease.
- Date of publication
- April 6, 2005
- DOI
- Identifier
- Resource type
- Article
- Rights statement
- In Copyright
- Rights holder
- Kuriko Kagitani-Shimono et al.; licensee BioMed Central Ltd.
- License
- Journal title
- Journal of Neuroinflammation
- Journal volume
- 2
- Journal issue
- 1
- Page start
- 10
- Language
- English
- Is the article or chapter peer-reviewed?
- Yes
- ISSN
- 1742-2094
- Bibliographic citation
- Journal of Neuroinflammation. 2005 Apr 06;2(1):10
- Publisher
- BioMed Central Ltd
- Access right
- Open Access
- Date uploaded
- September 5, 2012
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