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【bio-news】血脑屏障损伤可致多发性硬化症严重化
04/09/07 -- Immunology researchers at the Kimmel Cancer Center at Jefferson studying a multiple sclerosis (MS)-like disease in mice have shown that the amount of ?damage? to the central nervous system?s protective blood-brain barrier ? in essence, opening it ? almost always correlates to the severity of the disease. The findings, reported online in the Proceedings of the National Academy of Sciences, can be used for testing potential MS therapies and for better understanding the role of the blood-brain barrier in disease processes.
Scientists led by D. Craig Hooper, Ph.D., associate professor of cancer biology at Jefferson Medical College of Thomas Jefferson University in Philadelphia, and Hilary Koprowski, M.D., professor of cancer biology at Jefferson Medical College and director of Jefferson?s Center for Neurovirology and the Biotechnology Foundation Laboratories, wanted to find out what factors might affect the onset and severity of EAE (experimental allergic encephalomyelitis), an MS-like autoimmune disease often used as a model. They studied various strains of mice, each lacking some genes associated with inflammation and immunity, and looked at what happened to the blood-brain barrier.
They discovered that the amount of blood-brain barrier damage and subsequent permeability increase correlated to the severity of disease, and surprisingly, in nearly every case, the mouse?s genetic make-up didn?t matter. The mice developed EAE even without supposedly crucial factors in inflammation and autoimmunity ? and disease.
?We?ve now shown in all of these mice missing certain components of the immune system that, as expected, opening the blood-brain barrier and letting cells and factors in from the circulation is critical to the development of disease,? Dr. Hooper says. ?The fact that the extent of the permeability change correlates with the severity of clinical disease signs shows that this is an important element in determining how sick these animals can get.
?This puts an emphasis on the fact that blood brain permeability changes are an important aspect of the development of a CNS inflammatory disease like EAE, an animal model of MS,? he says.
According to Dr. Hooper, previous studies by his group and other researchers have shown that blood-brain barrier permeability is critical in the development of MS. To study this permeability, he and his co-workers looked at a range of mice lacking certain genes for various types of immune system and inflammatory cells such as NF kappaB, TNF-alpha, and interferon alpha, beta and gamma that contribute to disease. The researchers established EAE in each mouse strain and examined what was common to all of the animals when they developed disease.
?What?s astounding is that mice that wouldn?t be expected to develop EAE because they have major defects in their immune system are still able to develop disease,? though at different rates, he notes.
However, mice missing the immune protein TNF-alpha often did not show disease, despite the increase in brain barrier permeability, causing the scientists to speculate about its role in the disease. ?This is the first proof that there are permeability changes in all of these animals and the first hint that permeability doesn?t always equal disease,? he says.
Dr. Hooper notes that the work is part of the long-range goal of determining the exact role of blood-brain barrier permeability in disease. ?These results tell us a great deal about the mechanisms that damage the blood-brain barrier,? he says. ?All of these factors that are missing in the mice aren?t essential to opening the blood brain barrier.?
Source: Thomas Jefferson University
http://www.bio.com/newsfeatures/newsfeatures_research.jhtml;jsessionid=2FJXISJKXUCTTR3FQLMCFEWHUWBNSIV0?cid=28200007 本人已认领该文，如48小时后未能提交译文，请其他站友自由认领^_^ LZ给出的原文和网上的原文中均有部分不可识别字符，我根据自己的理解进行了编译，请高手们指点，谢谢^_^ 血脑屏障损伤可致多发性硬化症严重化
2007年4月9日，Jefferson Kimmel肿瘤中心的免疫学研究者的一项关于小鼠的类MS疾病的研究表明，CNS损伤程度与BBB保护有关。事实上，BBB的开放几乎一直与疾病的严重程度相关。由国家科学院学报在线报导的这项发现，可以用以测试可能的MS治疗并可以更好的了解BBB在疾病进程中的作用。
由费城Thomas Jefferson大学Jefferson医学院肿瘤生物学副教授D. Craig Hooper及Jefferson医学院肿瘤生物学教授、Jefferson神经病毒学和生物技术基础实验室中心主任Hilary Koprowski带领的科学家们希望找出导致实验性变应性脑脊髓炎(EAE)起病及加重的因子，EAE其常被用作MS样自身免疫疾病研究的病理模型。他们对不同种属的具有某些与炎症和免疫相关基因缺损的小鼠进行了研究，观察它们BBB的变化。他们发现，BBB损害及继发的渗透性增加的程度都与疾病严重程度相关，但令人惊奇的是几乎每一例小鼠的基因改变都与其无关。小鼠甚至在没有预想中的致炎和自身免疫疾病的关键因子的情况下发生了EAE。
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作者:admin@医学,生命科学 2010-12-01 05:11
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