恢复血脑屏障的完整性
英国一项研究发现，恢复血脑屏障的完整性可能有助于减缓并逆转诸如多发性硬化、阿尔兹海默病和帕金森病的发展。研究论文发表在2012年12月31日的美国《国家科学院院刊》（PNAS)上。
英国一项研究发现，恢复血脑屏障的完整性可能有助于减缓并逆转诸如多发性硬化、阿尔兹海默病和帕金森病的发展。研究论文发表在2012年12月31日的美国《国家科学院院刊》（PNAS)上。
几种退行性脑病能削弱血脑屏障——这是把血流和中枢神经系统的液体分隔开来的人体天然机制——因此也就让不适宜的分子进入了大脑，产生了灾难性的后果。Egle Solito及其同事确定了称为Annexin A1 (ANXA1)的基因产物调控着大脑内皮细胞的这种屏障的完整性，该基因就是在大脑内皮细胞表达的。
这组作者发现，缺乏ANXA1的小鼠表现出了这种屏障的完整性显著减少，这一发现可能有助于解释之前的研究所显示出的多发性硬化病人表现出的脑血管内皮的ANXA1选择性流失。此外，这组作者报告说，用人类重组ANXA1处理体外的脑血管内皮细胞能让恢复这种屏障完整性所需的细胞功能恢复。
这组作者说，ANXA1起到了血脑屏障关键调控者的作用，可能有潜力成为几种退行性神经疾病的疗法的靶标。
Abstract
The blood–brain barrier (BBB), a critical guardian of communication between the periphery and the brain, is frequently compromised in neurological diseases such as multiple sclerosis (MS), resulting in the inappropriate passage of molecules and leukocytes into the brain. Here we show that the glucocorticoid anti-inflammatory messenger annexin A1 (ANXA1) is expressed in brain microvascular endothelial cells, where it regulates BBB integrity. In particular, ANXA1−/− mice exhibit significantly increased BBB permeability as a result of disrupted interendothelial cell tight junctions, essentially related to changes in the actin cytoskeleton, which stabilizes tight and adherens junctions. This situation is reminiscent of early MS pathology, a relationship confirmed by our detection of a selective loss of ANXA1 in the plasma and cerebrovascular endothelium of patients with MS. Importantly, this loss is swiftly restored by i.v. administration of human recombinant ANXA1. Analysis in vitro confirms that treatment of cerebrovascular endothelial cells with recombinant ANXA1 restores cell polarity, cytoskeleton integrity, and paracellular permeability through inhibition of the small G protein RhoA. We thus propose ANXA1 as a critical physiological regulator of BBB integrity and suggest it may have utility in the treatment of MS, correcting BBB function and hence ameliorating disease.
相关文章
评论
我要跟帖
.jpg)
