Fabis Marzena J, Scott Gwen S, Kean Rhonda B, Koprowski Hilary, Hooper D Craig
Center for Neurovirology, Department of Cancer Biology, Biotechnology Foundation Laboratories, Thomas Jefferson University, Philadelphia, PA 19107-6799, USA.
Proc Natl Acad Sci U S A. 2007 Mar 27;104(13):5656-61. doi: 10.1073/pnas.0701252104. Epub 2007 Mar 19.
Experimental allergic encephalomyelitis (EAE) is an inflammatory demyelinating disease of the CNS that is used to model certain parameters of multiple sclerosis. To establish the relative contributions of T cell reactivity, the loss of blood-brain barrier (BBB) integrity, CNS inflammation, and lesion formation toward the pathogenesis of EAE, we assessed the incidence of EAE and these parameters in mice lacking NF-kappaB, TNF-alpha, IFN-alphabeta receptors, IFN-gamma receptors, and inducible nitric oxide synthase. Although increased myelin oligodendrocyte glycoprotein-specific T cell reactivity was generally associated with a more rapid onset or increased disease severity, the loss of BBB integrity and cell accumulation in spinal cord tissues was invariably associated with the development of neurological disease signs. Histological and real-time RT-PCR analyses revealed differences in the nature of immune/inflammatory cell accumulation in the spinal cord tissues of the different mouse strains. On the other hand, disease severity during the acute phase of EAE directly correlated with the extent of BBB permeability. Thus, the loss of BBB integrity seems to be a requisite event in the development of EAE and can occur in the absence of important inflammatory mediators.
实验性自身免疫性脑脊髓炎（EAE）是一种中枢神经系统的炎性脱髓鞘疾病，用于模拟多发性硬化症的某些参数。为了确定T细胞反应性、血脑屏障（BBB）完整性丧失、中枢神经系统炎症和病变形成对EAE发病机制的相对贡献，我们评估了缺乏核因子κB、肿瘤坏死因子-α、干扰素-αβ受体、干扰素-γ受体和诱导型一氧化氮合酶的小鼠中EAE的发病率以及这些参数。虽然髓鞘少突胶质细胞糖蛋白特异性T细胞反应性增加通常与发病更快或疾病严重程度增加相关，但BBB完整性丧失和脊髓组织中的细胞积聚总是与神经疾病体征的发展相关。组织学和实时逆转录-聚合酶链反应分析揭示了不同小鼠品系脊髓组织中免疫/炎性细胞积聚性质的差异。另一方面，EAE急性期的疾病严重程度与BBB通透性程度直接相关。因此，BBB完整性丧失似乎是EAE发展过程中的一个必要事件，并且可以在没有重要炎性介质的情况下发生。
