Macrophage-depletion induced impairment of experimental CNS remyelination is associated with a reduced oligodendrocyte progenitor cell response and altered growth factor expression
- 作者：Kotter ; Mark R. ; Zhao ; Chao ; van Rooijen ; Nico ; Franklin ; Robin J.M.
- 关键词：Remyelination ; Inflammation ; Oligodendrocyte progenitor cells ; Macrophages ; Growth factors ; Phagocytosis ; Demyelination ; Regeneration
- 刊名：Neurobiology of Disease
- 出版年：2005
- 期刊代码：80_09699961
- 类别：neu
- 出版时间：February, 2005
- 卷：18
- 期：1
- 页码：166-175
- 文件大小：420 K
摘要
Although macrophages are mediators of CNS demyelination, they are also implicated in remyelination. To examine the role of macrophages in CNS remyelination, adult rats were depleted of monocytes using clodronate liposomes and demyelination induced in the spinal cord white matter using lysolecithin. In situ hybridization for scavenger receptor-B and myelin basic protein (MBP) revealed a transiently impaired macrophage response associated with delayed remyelination in liposome-treated animals. Macrophage reduction corresponded with delayed recruitment of PDGFR脦脦+ oligodendrocyte progenitor cells (OPCs), which preceded changes in myelin phagocytosis, indicating a macrophage effect on OPCs independent of myelin debris clearance. Macrophage-depletion induced changes in the mRNA expression of insulin-like growth factor-1 and transforming growth factor 脦脦1, but not platelet-derived growth factor-A and fibroblast growth factor-2. These data suggest that the macrophage response to toxin-induced demyelination influences the growth factor environment, thereby affecting the behavior of OPCs and hence the efficiency of remyelination.