2005 Fiscal Year Final Research Report Summary
Analysis on behavior of oligodendrocyte progenitor cells after cerebral ischemia-From the view point of regenerative medicine
| Project/Area Number |
16590847
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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 | University of Toyama (2005)
Keio University (2004) |
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Principal Investigator |
TANAKA Kortaro Toyama University Hospital, Department of Neurology, Professor, 附属病院, 教授 (90129528)
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| Project Period (FY) |
2004 – 2005
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| Keywords | oligodendrocyte progenitor cell / cerebral ischemia / demyelination / remyelination / regeneration |
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| Research Abstract |
Vulnerability of oligodendrocytes to ischemic stress with acute ischemia-induced demyelination has recently been elucidated. Oligodendrocyte progenitor cells (OPCs), which are found not only during development but remain abundant in the gray and the white matter in the adult brain, retain the potential to mature into myelinating oligodendrocytes in various situations such as experimental demyelination models. Recent studies also reported that OPCs are virtually multipotent progenitor cells that can differentiate into not only oligodendrocytes but also neurons and astrocytes.
We examined the temporal and regional profiles of OPCs during recirculation after focal cerebral ischemia in the adult rat brain. Focal cerebral ischemia was induced by 90-min occlusion of the middle cerebral artery with intraluminal filament method. The peri-infarct area exhibited a significant reduction in the number of mature oligodendrocytes and the myelin density with a slight increase in the number of OPCs after 48-hour recirculation. Subsequently, the number of OPCs was progressively increased with a gradual recovery of the number of mature oligodendrocytes and the myelin density in the peri-infarct area, resulting in almost complete restoration of myelin density at 2 weeks of recirculation. OPCs exhibited characteristic morphological changes such as mitotic figures, monopolar or bipolar shapes, and hypertrophied cell bodies and processes, all indicating active cell proliferation, migration and maturation. These profiles were noted similarly in the gray and the white matter belonging to the peri-infarct area, and were accompanied with sustained phosphorylation of CREB (cyclic AMP response element binding protein) in the nuclei of OPCs.
These findings suggest that OPCs contribute to replenishment of mature myelinating oligodendrocytes and resultant remyelination in the peri-infarct area after ischemic insult.
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