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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 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。到目前为止，还不可能在尸检前容易地确定一个人是否患有蜂房/SIVE。我们检测了感染SIV的猕猴血清中星形胶质蛋白S100B的水平，结果表明，不仅可以在死后确定相关因素，还可以预测哪些人会患上SIVE。血清S100B蛋白升高的动物，与SIVE病变相关的脑微血管上ZO-1的表达也减少，血管周围血浆蛋白纤维蛋白原的表达减少。综上所述，这些数据表明SIVE病变与血管渗漏有关，外周S100B蛋白可以监测到血管渗漏。能够简单和前瞻性地监测SIVE的发展将极大地促进对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 had HIVE/SIVE before post mortem examination. We have examined serum levels of the astroglial protein S100b in SIV-infected macaques and show that it is possible not only to determine correlates post mortem, but also to predict which individuals will develop SIVE. Animals with increased S100b protein in serum also had decreased expression of zo-1 on brain microvessels spatially related to SIVE lesions and perivascular expression of plasma protein 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.