S100BETA AS A DETERMINANT FOR DEVELOPMENT OF MONOCYTE-DRIVEN ENCEPHALITIS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 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，表明它可以用来预测哪些动物会患上SIVE。我们还发现，血清中S100B蛋白的增加与脑微血管紧密连接蛋白闭锁带-1的表达减少有关。此外，闭锁带-1表达的减少与SIVE损害和血管周围血浆纤维蛋白原沉积在空间上有关。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. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.