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A New Targeted Model of Experimental Autoimmune Encephalomyelitis in the Common Marmoset

机译:普通Mar猴实验性自身免疫性脑脊髓炎的新型靶向模型

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摘要

Multiple sclerosis (MS) is the most common cause for sustained disability in young adults, yet treatment options remain very limited. Although numerous therapeutic approaches have been effective in rodent models of experimental autoimmune encephalomyelitis (EAE), only few proved to be beneficial in patients with MS. Hence, there is a strong need for more predictive animal models. Within the past decade, EAE in the common marmoset evolved as a potent, alternative model for MS, with immunological and pathological features resembling more closely the human disease. However, an often very rapid and severe disease course hampers its implementation for systematic testing of new treatment strategies. We here developed a new focal model of EAE in the common marmoset, induced by myelin oligodendrocyte glycoprotein (MOG) immunization and stereotactic injections of proinflammatory cytokines. At the injection site of cytokines, confluent inflammatory demyelinating lesions developed that strongly resembled human MS lesions. In a proof-of-principle treatment study with the immunomodulatory compound laquinimod, we demonstrate that targeted EAE in marmosets provides a promising and valid tool for preclinical experimental treatment trials in MS research.
机译:多发性硬化症(MS)是年轻人持续残疾的最常见原因,但治疗选择仍然非常有限。尽管许多治疗方法已在实验性自身免疫性脑脊髓炎(EAE)的啮齿动物模型中有效,但只有极少数被证明对MS患者有益。因此,强烈需要更具预测性的动物模型。在过去的十年中,普通mar猴中的EAE演变为MS的有效替代模型,其免疫学和病理学特征与人类疾病更为相似。然而,通常非常快速和严重的疾病过程阻碍了其对新治疗策略的系统测试的实施。我们在这里开发了由mar鼠少突胶质细胞糖蛋白(MOG)免疫接种和定向注射促炎细胞因子诱导的普通mar猴EAE的新病灶模型。在细胞因子的注射部位,出现了融合性炎症性脱髓鞘性病变,与人类MS病变非常相似。在使用免疫调节化合物拉喹莫德的原则治疗研究中,我们证明了针对targeted猴的EAE提供了有希望且有效的工具,可用于MS研究中的临床前实验治疗试验。

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