OXIDATIVE STRESS MARKERS AND HIV-ASSOCIATED NEUROLOGICAL DISORDERS

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。 艾滋病毒痴呆症(HIV-D)是美国年轻人痴呆症最常见的原因之一。中枢神经系统(CNS)内异常的免疫激活和氧化应激在HIV-D的发展中起着重要作用。细胞因子和氧化还原平衡的破坏会产生可攻击蛋白质、脱氧核酸和脂膜的活性氧物种，导致细胞功能障碍和细胞死亡。我们小组的最新数据显示，氧化应激的几个标记物增加，特别是神经酰胺、鞘磷脂和4-羟基壬烯醛(HNE)。 该项目将汇集一组患有不同程度神经认知障碍的HIV+个体：1)确定一组接受HAART治疗的受试者中氧化应激标志物与HIV-D之间的联系，并确定这些标志物与巨噬细胞和星形胶质细胞激活的实验室标志物以及炎症和神经元损伤的神经成像标志物之间的关系；2)确定氧化应激标志物是否预测HIV-D的可逆性或进展。

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. HIV dementia (HIV-D) is one of the most common causes of dementia in young adults in the United States. Aberrant immune activation and oxidative stress within the central nervous system (CNS) play a significant role in the development of HIV-D. Disruptions in cytokine and redox balance produce reactive oxygen species which can attack proteins, deoxynucleic acids, and lipid membranes resulting in cellular dysfunction and cell death. Recent data from our group demonstrate increases in several markers of oxidative stress, specifically, ceramide, sphingomyelin, and 4-hydroxynonenal (HNE). The project will assemble a cohort of HIV+ individuals with varying degrees of neurocognitive impairment: 1) to define the association between markers of oxidative stress and HIV-D in a cohort of HAART-treated subjects and to determine the relationship between these markers and laboratory markers of macrophage and astrocyte activation and neuroimaging markers of inflammation and neuronal injury, and 2) to determine whether markers of oxidative stress predict either the reversibility or the progression of HIV-D.