Clinicopathological study of a myelin oligodendrocyte glycoprotein-induced demyelinating disease in LEW.1AV1 rats
Clinicopathological study of a myelin oligodendrocyte glycoprotein-induced demyelinating disease in LEW.1AV1 rats
复制标题
DOI：
10.1093/brain/awh260
复制
发表时间：
2004-10-01
期刊：
影响因子：
14.5
通讯作者：
Matsumoto, Y
中科院分区：
文献类型：
--
作者：
Sakuma, H;Kohyama, K;Matsumoto, Y
虽然多发性硬化症被认为是中枢神经系统的自身免疫性疾病，但中枢神经系统和淋巴器官中发生的免疫反应仍有待阐明。在这里，我们已经成功地诱导各种亚型的实验性自身免疫性脑炎（EAE）的LEW. 1AV 1大鼠携带RT 1（av 1）的刘易斯背景基因的免疫重组大鼠髓鞘少突胶质细胞糖蛋白（MOG）在各种解决方案与佐剂。本研究的目的是更详细地分析MOG诱导的EAE LEW.1AV1大鼠的临床和免疫病理学特征。高剂量的可溶性MOG百日咳毒素免疫诱导急性，往往是致命的EAE，而中等剂量的部分聚集MOG无百日咳毒素产生复发和缓解EAE。用介于上述两种免疫方案之间的免疫方案在一些大鼠中诱导继发性进行性EAE。免疫组大鼠视神经（60%）和脊髓（100%）受累较重，大脑未见病变。组织学检查显示，尽管临床亚型多种多样，但病理过程的进展惊人地一致，即最初的炎症伴最小脱髓鞘，随后是主要的脱髓鞘伴最小淋巴细胞浸润。这些结果表明，在后期的损害是由体液因素维持。总之，该实验系统可以作为视神经肌萎缩症的模型。进一步的分析将为阐明视神经肌萎缩症和多发性硬化的发病机制和发展免疫治疗提供有用的信息。
Although multiple sclerosis is considered to be an autoimmune disease in the CNS, the immune responses that take place in the CNS and lymphoid organs remain to be elucidated. Here, we have successfully induced various subtypes of experimental autoimmune encephalitis (EAE) in LEW.1AV1 rats carrying RT1(av1) on the Lewis background genes by immunization with recombinant rat myelin oligodendrocyte glycoprotein (MOG) in various solutions with adjuvants. The purpose of the present study was to analyse in more detail the clinical and immunopathological features of MOG-induced EAE in LEW.1AV1 rats. Immunization with high doses of soluble MOG with pertussis toxin induced acute, frequently fatal EAE, whereas medium doses of partially aggregated MOG without pertussis toxin produced relapsing and remitting EAE. Secondary progressive EAE was induced in some rats by immunization with the immunization protocol having an intermediate nature between the above two. The optic nerve (similar to60% of the immunized rats) and spinal cord (100%) were frequently involved and detectable both clinically and pathologically, while there was no lesion in the cerebrum. Histological examination revealed that, despite variety in the clinical subtypes, progression of the pathological processes was strikingly uniform, i.e. initial inflammation with minimal demyelination followed by predominant demyelination with minimal lymphocyte infiltration. These findings suggest that the lesion during the later stage is maintained by humoral factors. Taken together, this experimental system can serve as a model of neuromyelitis optica. Further analysis will provide useful information to elucidate the pathogenesis and to develop immunotherapy for neuromyelitis optica and multiple sclerosis.