Extensive remyelination of the CNS leads to functional recovery
Extensive remyelination of the CNS leads to functional recovery
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DOI：
10.1073/pnas.0812500106
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发表时间：
2009-04-21
影响因子：
11.1
通讯作者：
Schultz, R. D.
中科院分区：
文献类型：
--
作者：
Duncan, I. D.;Brower, A.;Schultz, R. D.
在多发性硬化症中，中枢神经系统的髓鞘再形成被认为对恢复传导和保护轴突免于变性是重要的。然而，髓鞘再生在临床功能恢复中的作用尚未得到证实。在这里，我们表明，猫喂养的辐射饮食在怀孕期间开发了严重的神经系统疾病造成广泛的髓鞘空泡化和随后的脱髓鞘。尽管有严重的髓鞘变性，轴突基本上保持完整。少突胶质细胞系的细胞对脱髓鞘有迅速的内源性反应，同时发生髓鞘再生。恢复正常饮食的猫恢复得很慢，到3-4个月时，它们的神经功能正常。此时CNS的组织学检查显示广泛的髓鞘再生，这在几乎整个神经被髓鞘再生的视神经中尤其显著。受影响的猫的饮食和组织的生化分析显示，没有饮食不足或有毒物质积累。因此，尽管这种显著疾病的病因仍然未知，但它明确表明，在非免疫介导的脱髓鞘疾病中，轴突被保留的地方，髓鞘再生是CNS中的默认途径。最重要的是，它证实了髓鞘再生的临床相关性及其恢复功能的能力。
Remyelination of the CNS in multiple sclerosis is thought to be important to restore conduction and protect axons against degeneration. Yet the role that remyelination plays in clinical recovery of function remains unproven. Here, we show that cats fed an irradiated diet during gestation developed a severe neurologic disease resulting from extensive myelin vacuolation and subsequent demyelination. Despite the severe myelin degeneration, axons remained essentially intact. There was a prompt endogenous response by cells of the oligodendrocyte lineage to the demyelination, with remyelination occurring simultaneously. Cats that were returned to a normal diet recovered slowly so that by 3-4 months they were neurologically normal. Histological examination of the CNS at this point showed extensive remyelination that was especially notable in the optic nerve where almost the entire nerve was remyelinated. Biochemical analysis of the diet and tissues from affected cats showed no dietary deficiencies or toxic accumulations. Thus, although the etiology of this remarkable disease remains unknown, it shows unequivocally that where axons are preserved remyelination is the default pathway in the CNS in nonimmune-mediated demyelinating disease. Most importantly, it confirms the clinical relevance of remyelination and its ability to restore function.