Harrer Melanie D, von Büdingen Hans-Christian, Stoppini Luc, Alliod Chantal, Pouly Sandrine, Fischer Katja, Goebels Norbert
University Hospital Zurich, Department of Neurology, Neuroimmunology Unit, Frauenklinikstrasse 26, CH-8091 Zurich, Switzerland.
Exp Neurol. 2009 Apr;216(2):431-8. doi: 10.1016/j.expneurol.2008.12.027.
Mononuclear cell infiltrates, deposits of immunoglobulin and complement as well as demyelination and axonal damage are neuropathological hallmarks of Multiple Sclerosis (MS) lesions. An involvement of antibodies is further suggested by the presence of oligoclonal immunoglobulins in the cerebrospinal fluid of almost all MS patients. However, which mechanisms are most relevant for de- and remyelination and axonal loss in MS lesions is poorly understood. To characterize the regenerative abilities of demyelinated CNS tissue, we utilized murine organotypic cerebellar slice cultures expressing GFP in oligodendrocytes. The addition of a demyelinating monoclonal antibody specific for myelin oligodendrocyte glycoprotein and complement induced complete myelin destruction and oligodendrocyte loss, as demonstrated by confocal live imaging and staining for different myelin proteins. After removal of antibodies and complement we visualized the stages of remyelination, presumably originating from proliferating oligodendrocyte precursor cells and guided by morphologically intact appearing axons. Allowing for the detailed live imaging of de- and remyelination in an ex vivo situation closely resembling the three dimensional cytoarchitecture of the CNS, we provide a useful experimental system for the evaluation of new therapeutic strategies to enhance remyelination and repair in MS.
单核细胞浸润、免疫球蛋白和补体沉积以及脱髓鞘和轴突损伤是多发性硬化症（MS）病变的神经病理学特征。几乎所有MS患者脑脊液中存在寡克隆免疫球蛋白，进一步提示抗体参与其中。然而，对于MS病变中脱髓鞘和再髓鞘化以及轴突丢失最相关的机制，人们了解甚少。为了表征脱髓鞘中枢神经系统组织的再生能力，我们利用在少突胶质细胞中表达绿色荧光蛋白（GFP）的小鼠小脑器官型切片培养物。如共聚焦实时成像和针对不同髓鞘蛋白的染色所示，添加针对髓鞘少突胶质细胞糖蛋白的脱髓鞘单克隆抗体和补体可导致完全的髓鞘破坏和少突胶质细胞丢失。去除抗体和补体后，我们观察到再髓鞘化阶段，推测其源自增殖的少突胶质细胞前体细胞，并由形态上看似完整的轴突引导。鉴于能够在与中枢神经系统三维细胞结构极为相似的体外环境中对脱髓鞘和再髓鞘化进行详细的实时成像，我们提供了一个有用的实验系统，用于评估增强MS再髓鞘化和修复的新治疗策略。
