Neuroinflammation Research Center, Department of Neuroscience, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Nat Neurosci. 2010 Mar;13(3):319-26. doi: 10.1038/nn.2491. Epub 2010 Feb 14.
Multiple sclerosis is an inflammatory demyelinating disorder of the CNS. Recent studies have suggested diverse mechanisms as underlying demyelination, including a subset of lesions induced by an interaction between metabolic insult to oligodendrocytes and inflammatory mediators. For mice of susceptible strains, cuprizone feeding results in oligodendrocyte cell loss and demyelination of the corpus callosum. Remyelination ensues and has been extensively studied. Cuprizone-induced demyelination remains incompletely characterized. We found that mice lacking the type 2 CXC chemokine receptor (CXCR2) were relatively resistant to cuprizone-induced demyelination and that circulating CXCR2-positive neutrophils were important for cuprizone-induced demyelination. Our findings support a two-hit process of cuprizone-induced demyelination, supporting the idea that multiple sclerosis pathogenesis features extensive oligodendrocyte cell loss. These data suggest that cuprizone-induced demyelination is useful for modeling certain aspects of multiple sclerosis pathogenesis.
多发性硬化症是一种中枢神经系统的炎症性脱髓鞘疾病。最近的研究表明，多种机制是脱髓鞘的基础，包括由少突胶质细胞代谢损伤与炎症介质相互作用引起的病变亚群。对于易感品系的小鼠，喂食铜蓝蛋白会导致少突胶质细胞丧失和胼胝体脱髓鞘。随后会发生髓鞘再生，并对此进行了广泛研究。铜蓝蛋白诱导的脱髓鞘仍然没有完全被描述。我们发现，缺乏 2 型 CXC 趋化因子受体（CXCR2）的小鼠对铜蓝蛋白诱导的脱髓鞘相对具有抗性，而循环 CXCR2 阳性中性粒细胞对铜蓝蛋白诱导的脱髓鞘很重要。我们的发现支持铜蓝蛋白诱导的脱髓鞘的双打击过程，支持多发性硬化症发病机制的特征是广泛的少突胶质细胞丧失的观点。这些数据表明，铜蓝蛋白诱导的脱髓鞘对于模拟多发性硬化症发病机制的某些方面是有用的。
