| Project/Area Number |
18590936
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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 | Tazuke Kofukai Medical Research Institute |
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Principal Investigator |
SAIKI Hidemoto Tazuke Kofukai Medical Research Institute, 4 Division, Medical Research Institute, Researcher (90378688)
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| Co-Investigator(Kenkyū-buntansha) |
TOMIMOTO Hidekazu Kyoto University, Graduate School of Medicine, Lecturer (80324648)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,810,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2006: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Keywords | white matter lesions / chronic cerebral hypoperfusion / blood-brain barrier / knockout mouse / basement membrane / extracellular matrix / subcortical vascular dementia / matrix metalloproteinase(MMP) / マトリックスメタロプロテァーゼ / マウス / 慢性脳低灌流モデル |
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| Research Abstract |
White matter lesions are closely associated with cognitive impairment and motor dysfunction in the aged. To explore the pathophysiology of these lesions, we examined the expression of matrix metalloproteinase (MMP)-2 and MMP-9 in the white matter in a rat model of chronic cerebral hypoperfusion. After bilateral clipping of the common carotid arteries, myelin staining revealed demyelinating changes in the optic tract and the corpus callosum on day 7. Zymographic analyses indicated an increase in the level of MMP-2, but not MMP-9, after the hypoperfusion. Immunohistochemical analyses revealed the presence of MMP-2-expressing activated microglia in the optic tract and corpus callosum, most numerously on day 3. In contrast, the capillary endothelial cells expressed MMP-2 later.
IgM-immunoreactive glial cells were absent in the sham operated animals, but were present in the hypoperfused animals by day 3, reflecting the disrupted blood-brain barrier. These findings suggest that the main sources of the elevated MMP-2 were the microglia and the endothelium, and that these cells may contribute to the remodeling of the white matter myelin and microvascular beds in chronic cerebral hypoperfusion.
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