Tonra James R
Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts 02139, USA.
Cerebellum. 2002 Jan-Mar;1(1):57-68. doi: 10.1080/147342202753203096.
Experimental autoimmune encephalomyelitis (EAE) is utilized as an animal model for multiple sclerosis (MS). In both EAE and MS, activated T-lymphocytes specific for self-antigens present in myelin are linked to CNS inflammation and the breakdown of the blood-brain barrier (BBB) to peripheral blood leukocytes and plasma proteins, predominately in myelin rich white matter. One aspect of MS that has received relatively little attention is the finding that certain CNS regions are more likely than others to develop disease in different patient populations. Understanding the factors predisposing specific brain regions to autoimmune attack, or protecting other regions, would provide a better understanding of the disease as a process, and may also offer additional targets for therapeutic development. EAE offers a model to search for these factors and the first step in such a process is to identify the brain regions that are susceptible to EAE. Until recently the spinal cord in rodents has been considered the region most susceptible to EAE, with disease in more rostral regions occurring later and with reduced severity. However a more recent study has shown that the cerebellum of SJL/J mice, like the spinal cord, is especially susceptible to BBB breakdown in EAE. Although many factors known to be involved in BBB formation and breakdown remain to be assessed for their possible role in increasing the susceptibility of the cerebellum, one potentially important factor is the location of venules, which are the most affected vascular elements in inflamed tissue. There is a prevalence of large EAE susceptible venules traveling in the myelin rich white matter tracts in SJL/J mouse cerebellar cortex, indicating that the vascularization of this tissue may contribute to the increased susceptibility to inflammation in response to autoimmune attacks directed against CNS myelin.
实验性自身免疫性脑脊髓炎（EAE）被用作多发性硬化症（MS）的动物模型。在EAE和MS中，针对髓鞘中自身抗原的活化T淋巴细胞与中枢神经系统炎症以及血脑屏障（BBB）向外周血白细胞和血浆蛋白的破坏有关，主要发生在富含髓鞘的白质中。MS的一个相对较少受到关注的方面是，在不同患者群体中，某些中枢神经系统区域比其他区域更容易发生疾病。了解使特定脑区易受自身免疫攻击或保护其他区域的因素，将有助于更好地理解该疾病的发病过程，也可能为治疗开发提供更多靶点。EAE提供了一个寻找这些因素的模型，而这一过程的第一步是确定易患EAE的脑区。直到最近，啮齿动物的脊髓一直被认为是最易患EAE的区域，而更靠前区域的疾病发生较晚且严重程度较低。然而，最近的一项研究表明，SJL/J小鼠的小脑与脊髓一样，在EAE中特别容易发生血脑屏障破坏。尽管许多已知参与血脑屏障形成和破坏的因素在增加小脑易感性方面的可能作用仍有待评估，但一个潜在的重要因素是小静脉的位置，小静脉是炎症组织中受影响最大的血管成分。在SJL/J小鼠小脑皮质富含髓鞘的白质束中有大量易患EAE的小静脉，这表明该组织的血管化可能导致对针对中枢神经系统髓鞘的自身免疫攻击的炎症易感性增加。
