Endogenous cell repair of chronic demyelination.
Endogenous cell repair of chronic demyelination.
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DOI：
10.1097/01.jnen.0000205142.08716.7e
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发表时间：
2006-03
影响因子：
3.2
通讯作者：
Zhou YX
中科院分区：
文献类型：
--
作者：
Armstrong RC;Le TQ;Flint NC;Vana AC;Zhou YX
在多发性硬化症病变中，髓鞘再生通常因反复或慢性脱髓鞘发作而失败，并导致神经功能障碍。啮齿类动物的急性脱髓鞘模型通常表现出强大的自发髓鞘再生，这阻碍了对改善髓鞘再生不足状况的策略的适当评估。在目前的研究中，我们使用了慢性脱髓鞘的小鼠模型连续摄入0.2%的cuprizone 12周。这个慢性过程耗尽了少突胶质细胞祖细胞群并损害了少突胶质细胞再生。从饮食中去除cuprizone后，再髓鞘形成仍然有限。成纤维细胞生长因子2（FGF 2）的表达持续增加，在胼胝体的慢性脱髓鞘的小鼠相比，nonlesioned小鼠。我们使用FGF 2 −/−小鼠来确定内源性FGF 2的去除是否促进慢性脱髓鞘区域的髓鞘再生。野生型和FGF 2 −/−小鼠在慢性铜腙治疗期间表现出相似的脱髓鞘。重要的是，与野生型小鼠相反，FGF 2 −/−小鼠在慢性脱髓鞘后的恢复期内自发地完全再生髓鞘。FGF 2 −/−小鼠髓鞘再生增加与少突胶质细胞再生增强相关。FGF 2基因型不改变慢性脱髓鞘后少突胶质祖细胞或增殖细胞的密度。这些发现表明，减弱FGF 2为内源性细胞创造了足够宽松的损伤环境，即使在慢性脱髓鞘后也能有效地使有活力的轴突再生髓鞘。
In multiple sclerosis lesions, remyelination typically fails with repeated or chronic demyelinating episodes and results in neurologic disability. Acute demyelination models in rodents typically exhibit robust spontaneous remyelination that prevents appropriate evaluation of strategies for improving conditions of insufficient remyelination. In the current study, we used a mouse model of chronic demyelination induced by continuous ingestion of 0.2% cuprizone for 12 weeks. This chronic process depleted the oligodendrocyte progenitor population and impaired oligodendrocyte regeneration. Remyelination remained limited after removal of cuprizone from the diet. Fibroblast growth factor 2 (FGF2) expression was persistently increased in the corpus callosum of chronically demyelinated mice as compared with nonlesioned mice. We used FGF2−/− mice to determine whether removal of endogenous FGF2 promoted remyelination of chronically demyelinated areas. Wild-type and FGF2−/− mice exhibited similar demyelination during chronic cuprizone treatment. Importantly, in contrast to wild-type mice, the FGF2−/− mice spontaneously remyelinated completely during the recovery period after chronic demyelination. Increased remyelination in FGF2−/− mice correlated with enhanced oligodendroglial regeneration. FGF2 genotype did not alter the density of oligodendrocyte progenitor cells or proliferating cells after chronic demyelination. These findings indicate that attenuating FGF2 created a sufficiently permissive lesion environment for endogenous cells to effectively remyelinate viable axons even after chronic demyelination.