Studies on factors accounting for remyelination in the central nervous system

利用ICR小鼠小脑器官型培养，我们研究了tnf - α对髓鞘形成及其脱髓鞘作用的影响。成熟的髓鞘培养物对tnf - α具有抗性，即使在最高浓度（1x4^4U/ml）时也是如此。然而，当培养物从外植开始就在含有tnf - α的培养基中生长时，当浓度为1x10^2U/ml时，髓磷脂的形成受到显著影响。这些结果表明，tnf - α可能参与急性髓磷脂破坏后的再髓鞘生成阻滞。多发性硬化症（MS）的慢性脱髓鞘斑块的特征是少突胶质细胞星形胶质增生的丧失，以及不完全或没有再髓鞘再生，这可能部分是由于胶质星形胶质细胞对髓鞘形成的抑制作用。我们将小鼠小脑移植到维持2 ~ 12周的星形胶质细胞培养物上，并在移植后18天评估小脑组织中的髓鞘形成情况。2 ~ 4周龄星形胶质细胞外植的组织髓鞘形成旺盛，而4周龄以上星形胶质细胞外植的组织髓鞘形成较弱。12周龄星形胶质细胞未形成髓鞘，但轴突发育与2周龄星形胶质细胞相同。随着星形胶质细胞维持时间的延长，它们变得纤维化，抗胶质纤维酸性蛋白抗体的免疫染色更深，类似于星形胶质细胞形成。这些发现表明，多发性硬化症慢性脱髓鞘病变中的星形胶质增生可能会潜在地阻止髓鞘再生。

Using organotypic cultures of ICR mouse cerebellum, we studied the effects of TNF-alpha on myelin formation, and its demyelinating effects. Mature, myelinated cultures were resistant to TNF-alpha, even at the highest concentration examined, 1x4^4U/ml. However, when cultures were grown in medium containing TNF-alpha from the time of explantation, myelin formation was significantly affected at a concentration of 1x10^2U/ml. These results suggest that TNF-alpha may be involved in the remyelination block following acute myelin breakdown.The chronic demyelinated plaque of multiple sclerosis (MS) is characterized by a loss of oligodendrocyteastrogliosis, and incomplete or no remyelinatio which probably results in part from the suppressive effects of gliotic astrocytes on myelin formation. We explanted mouse cerebella on astrocyte cultures which had benn maintained for 2 to 12 weeks and assessed the myelination in the cerebellar tissue at 18 days after explantaion. Myelination occurred vigorously in the tissue explanted on 2- to 4-week-old astrocytes, but was poorer in the tissue explanted on astrocytes older than 4 weeks. No myelin sheath was formed on 12-week-old astrocytes, although axons developed equally as well as those in the tissues explanted on 2-week-old astrocytes. As astrocytes were maintained longer, they become fibrous and immunostained more deeply with anti-glial fibrillary acidic protein antibody, being analogous to astrogliosis. These findings imply that astrogliosis in chronic demyelinated lesions of MS may potentially block remyelination.