S100BETA, AS A DETERMINANT FOR DEVELOPMENT OF MONOCYTE-DRIVEN ENCEPHALITIS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 HIV/SIV脑炎（HIVE/SIVE）的发病机制仍不完全清楚，但与血脑屏障（BBB）的改变有关。因此，在尸检前不可能轻易确定一个人是否患有蜂巢/SIVE。 我们检测了SIV感染的猕猴的星形胶质细胞蛋白S100 b的血清水平，并表明它可以用来预测哪些动物将发展SIVE。我们还发现血清中S100 b蛋白的增加与脑微血管上紧密连接蛋白紧密连接蛋白1的表达减少相关。 此外，闭锁小带-1表达的减少在空间上与SIVE病变和血浆纤维蛋白原的血管周围沉积相关。总之，这些数据表明SIVE病变与血管渗漏相关，可以通过外周中的S100 b蛋白进行监测。 简单和前瞻性地监测SIVE发展的能力将极大地促进艾滋病神经发病机制的研究。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The pathogenesis of HIV/SIV encephalitis (HIVE/SIVE) remains incompletely understood, but is associated with alterations in the blood brain barrier (BBB). Heretofore, it has not been possible to easily determine if an individual has HIVE/SIVE before post mortem examination. We have examined serum levels of the astroglial protein S100b in SIV-infected macaques and show that it can be used to predict which animals will develop SIVE. We also found that increased S100b protein in serum correlated with decreased expression of the tight junction protein zonula occludens-1 on brain microvessels. Further, the decrease in zonula occldens-1 expression was spatially related to SIVE lesions and perivascular deposition of plasma fibrinogen. Together these data indicate that SIVE lesions are associated with vascular leakage that can be monitored by S100b protein in the periphery. The ability to simply and prospectively monitor the development of SIVE will greatly facilitate studies of the neuropathogenesis of AIDS.