2007 Fiscal Year Final Research Report Summary
Pathogenesis of ischemic white matter lesions ; an analysis using a novel mouse model for vascular dementia.
| 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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| Keywords | white matter lesions / chronic cerebral hypoperfusion / blood-brain barrier / knockout mouse / basement membrane / extracellular matrix / subcortical vascular dementia / matrix metalloproteinase(MMP) |
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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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Research Products
(10 results)
