Ischemic damage and subsequent proliferation of oligodendrocytes in focal cerebral ischemia
Section snippets
Animal preparation
Adult male C57BL/6 mice (Charles River Laboratories), weighing 21–25 g, were used. The experimental protocols have been approved by the Institutional Animal Care and Use Committee of Osaka University Medical School and were carried out in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals. All animals had free access to water and food until the day of surgery. They were maintained in an air-conditioned room at a constant temperature of 25°C and
Results
In the normal mouse cerebellum, the immunoreactivity for MBP was localized in the corpus medullare and the lamina albae, while PLP mRNA signals were localized in the round- to oval-shaped cells, mainly in the white matter. The nuclei of those cells were smaller than those of neurons. With the sense probe, no signal was detected. The results were consistent with the previous findings which showed that PLP mRNA signals were effectively confined to the perinuclear region of oligodendrocytes.1, 45
Discussion
The molecular mechanism causing ischemic white matter lesions still remains obscure, even though it is said to be the central pathophysiology for Binswanger's disease, cerebrovascular dementia [2]and periventricular leukomalacia.[46]In particular, it is not yet clear whether oligodendrocytes are the primary target of ischemic insults or whether they are destroyed together with myelin during active destruction of the white matter. Several investigators, using experimental rodent models of
Conclusions
Although the existence of 0-2A progenitor cells and immature oligodendrocytes in and around infarction must be examined, the present results strongly suggest the involvement of oligodendrocytes in the repair process after brain injury, and raise the possibility for a future therapeutic intervention to modify oligodendrocytic accumulation as well as macrophages/microglia and astrocytes[32]after brain injury.
Acknowledgements
The present work was supported in part by a Grant-in-Aid from the Ministry of Education, Science and Culture and by Health Science Research Grants from the Ministry of Health and Welfare of Japan. We are grateful to Megumi Shimomura, Reiko Manabe and Mizuki Tsunoda for their secretarial assistance.
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