Myelin debris regulates inflammatory responses in an experimental demyelination animal model and multiple sclerosis lesions
Myelin debris regulates inflammatory responses in an experimental demyelination animal model and multiple sclerosis lesions
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DOI：
10.1002/glia.22367
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发表时间：
2012-10-01
期刊：
影响因子：
6.2
通讯作者：
Kipp, Markus
中科院分区：
文献类型：
--
作者：
Clarner, Tim;Diederichs, Felix;Kipp, Markus
在多发性硬化症（MS）中，与白质病变相比，灰质病理的特点是不太明显的炎症。尽管细胞结构的区域差异可能解释了这些差异，但脱髓鞘事件中皮层髓磷脂碎片的数量也可能起作用。为了分析髓磷脂碎片水平与炎症反应之间的关系，我们分析了铜酮诱导的小鼠脱髓鞘前后具有明显和稀疏髓鞘形成的皮质区域的微胶质细胞和星形胶质细胞形成。在MS患者的死后组织中，评估白质皮层病变的类型和炎症水平，在皮层和白质区域的病变。此外，向小鼠脑内注射富含髓磷脂的碎片，并分析白质和灰质区域的炎症反应。我们的研究表明，髓磷脂损失的大小与铜酮模型中的小胶质细胞增生呈正相关。在MS中，与白质病变的灰质部分相比，白色部分表达MHC II类细胞的数量更高。最后，将髓磷脂碎片直接应用于小鼠的胼胝体或皮层，可在这两个区域引起严重的类似炎症。我们的数据表明，髓鞘碎片是脱髓鞘事件中炎症反应的重要变量。髓磷脂驱动的炎症是否影响神经元的完整性仍有待澄清。(c) 2012 Wiley期刊有限公司
In multiple sclerosis (MS), gray matter pathology is characterized by less pronounced inflammation when compared with white matter lesions. Although regional differences in the cytoarchitecture may account for these differences, the amount of myelin debris in the cortex during a demyelinating event might also be contributory. To analyze the association between myelin debris levels and inflammatory responses, cortical areas with distinct and sparse myelination were analyzed for micro- and astrogliosis before and after cuprizone-induced demyelination in mice. In postmortem tissue of MS patients, leucocortical lesions were assessed for the type and level of inflammation in the cortical and white matter regions of the lesion. Furthermore, mice were injected intracerebrally with myelin-enriched debris, and the inflammatory response analyzed in white and grey matter areas. Our studies show that the magnitude of myelin loss positively correlates with microgliosis in the cuprizone model. In MS, the number of MHC class II expressing cells is higher in the white compared with the grey matter part of leucocortical lesions. Finally, direct application of myelin debris into the corpus callosum or cortex of mice induces profound and comparable inflammation in both regions. Our data suggest that myelin debris is an important variable in the inflammatory response during demyelinating events. Whether myelin-driven inflammation affects neuronal integrity remains to be clarified. (c) 2012 Wiley Periodicals, Inc.