The blood-brain barrier in systemic lupus erythematosus
The blood-brain barrier in systemic lupus erythematosus
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DOI：
10.1191/0961203303lu501oa
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发表时间：
2003-01-01
期刊：
影响因子：
2.6
通讯作者：
Dolman, DEM
中科院分区：
文献类型：
--
作者：
Abbott, NJ;Mendonça, LLF;Dolman, DEM
中枢神经系统（CNS）受累可能发生在20-70%的系统性红斑狼疮（SLE）患者中，其中神经系统症状明显;这被称为神经精神性狼疮或NPSLE。本文综述了形成血脑屏障（BBB）的脑内皮细胞损伤是NPSLE的一个促成因素的证据。正常CNS在三个部位受到血液组织屏障的保护，即脑内皮（BBB）、脉络丛上皮（血液-CSF屏障）和蛛网膜上皮。屏障层的紧密连接严重限制了包括蛋白质在内的血浆成分的进入，使得CSF和脑间质液含有低水平的蛋白质。用于诊断BBB损伤的方法包括使用造影剂的成像（CT、MRI）和分析CSF的蛋白质含量和谱。白蛋白商Q（白蛋白）的变化显示屏障损伤的证据，而免疫球蛋白（IG）指数的变化可指示鞘内抗体产生。然而，BBB损伤可能是短暂的，因此未被检测到或被低估。机制研究很少，但BBB损伤的两个主要候选机制是脑血管中的微血栓导致缺血，以及免疫介导的内皮攻击和激活导致局部细胞因子产生。两者都可能导致屏障击穿。神经系统综合征可能继发于BBB损伤。NPSLE治疗的影响进行了讨论。
Central nervous system (CNS) involvement may occur in 20-70% of systemic lupus erythematosus (SLE) patients where neurological symptoms are overt; this is termed neuropsychiatric lupus or NPSLE. This review summarizes evidence that damage to the brain endothelium forming the blood-brain barrier (BBB) is a contributory factor in NPSLE. The normal CNS is protected by blood-tissue barriers at three sites, the brain endothelium (BBB), the choroid plexus epithelium (blood-CSF barrier) and the arachnoid epithelium. The tight junctions of the barrier layers severely restrict entry of plasma constituents including proteins, so that the CSF and brain interstitial fluid contain low levels of protein. Methods for diagnosing BBB damage include imaging (CT, MRI) using contrast agents, and analysing protein content and profiles of CSF. Changes in the albumin quotient Q(albumin) show evidence for barrier damage, while changes in the immunoglobulin (Ig) index can indicate intrathecal antibody production. However, BBB damage may be transient, and hence undetected or underestimated. Few mechanistic studies exist, but the two main candidate mechanisms for BBB damage are microthrombi in cerebral vessels leading to ischaemia, and immune-mediated attack and activation of the endothelium leading to local cytokine production. Both can result in barrier breakdown. Neurological syndromes could then be secondary to damage to the BBB. The implications for treatment of NPSLE are discussed.