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

S100BETA，作为单核细胞驱动性脑炎发展的决定因素

• 批准号: 8172980
• 负责人: ANDREW G MACLEAN
• 金额: $ 6.18万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172980
• 关键词: Acquired Immunodeficiency Syndrome; Animals; Blood - brain barrier anatomy; Blood Vessels; Brain; Computer Retrieval of Information on Scientific Projects Database; Data; Deposition; Development; Encephalitis; Extravasation; Fibrinogen; Funding; Grant; Individual; Institution; Lesion; Macaca; Monitor; Neuropathogenesis; Pathogenesis; Plasma; Research; Research Personnel; Resources; SIV encephalitis; Serum; Source; Tight Junctions; United States National Institutes of Health; Urticaria; monocyte; neurotrophic protein S100beta; zonula occludens-1 protein

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.

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，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。