Keirstead H S, Blakemore W F
MRC Cambridge Centre for Brain Repair and Department of Clinical Veterinary Medicine, University of Cambridge, UK.
J Neuropathol Exp Neurol. 1997 Nov;56(11):1191-201. doi: 10.1097/00005072-199711000-00003.
In order to investigate the remyelinating potential of mature oligodendrocytes in vivo, we have developed a model of demyelination in the adult rat spinal cord in which some oligodendrocytes survive demyelination. A single intraspinal injection of complement proteins plus antibodies to galactocerebroside (the major myelin sphingolipid) resulted in demyelination followed by oligodendrocyte remyelination. Remyelination was absent when the spinal cord was exposed to 40 Grays of x-irradiation prior to demyelination, a procedure that kills dividing cells. Quantitative Rip immunohistochemical analysis revealed a similar density of surviving oligodendrocytes in x-irradiated and nonirradiated lesions 3 days after demyelination. Rip and bromodeoxyuridine double immunohistochemical analysis of demyelinated lesions indicated that Rip+ oligodendrocytes did not divide as an acute response to demyelination. Oligodendrocytes were also identified by Rip immunostaining and electron microscopy at late time points (3 weeks) within x-irradiated areas of demyelination. These oligodendrocytes extended processes that engaged axons, and on occasion formed myelin membranes, but did not lay down new myelin sheaths. These studies demonstrate that (a) oligodendrocytes that survive within a region of demyelination are not induced to divide in the presence of demyelinated axons, and (b) fully-differentiated oligodendrocytes are therefore postmitotic and do not contribute to remyelination in the adult CNS.
为了研究成熟少突胶质细胞在体内的髓鞘再生潜力，我们建立了成年大鼠脊髓脱髓鞘模型，其中一些少突胶质细胞在脱髓鞘后存活下来。脊髓内单次注射补体蛋白加半乳糖脑苷脂（主要的髓鞘鞘脂）抗体导致脱髓鞘，随后少突胶质细胞进行髓鞘再生。在脱髓鞘前对脊髓进行40戈瑞的X射线照射（该过程会杀死分裂细胞）后，髓鞘再生缺失。定量Rip免疫组织化学分析显示，脱髓鞘3天后，X射线照射和未照射损伤中存活的少突胶质细胞密度相似。对脱髓鞘损伤进行Rip和溴脱氧尿苷双重免疫组织化学分析表明，Rip +少突胶质细胞不会作为对脱髓鞘的急性反应而分裂。在脱髓鞘的X射线照射区域的后期（3周），通过Rip免疫染色和电子显微镜也鉴定出了少突胶质细胞。这些少突胶质细胞伸出与轴突相连的突起，偶尔形成髓鞘膜，但不会形成新的髓鞘。这些研究表明：（a）在脱髓鞘区域内存活的少突胶质细胞在存在脱髓鞘轴突的情况下不会被诱导分裂；（b）因此，完全分化的少突胶质细胞是有丝分裂后细胞，对成年中枢神经系统的髓鞘再生没有贡献。
