OXIDATIVE STRESS MARKERS AND HIV-ASSOCIATED NEUROLOGICAL DISORDERS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。艾滋病毒痴呆（HIV- d）是美国年轻人痴呆症的最常见原因之一。异常免疫激活和中枢神经系统（CNS）的氧化应激在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产生活性氧，可攻击蛋白质、脱氧核酸和脂质膜，导致细胞功能障碍和细胞死亡。我们小组最近的数据表明，氧化应激的几种标志物，特别是神经酰胺、鞘磷脂和4-羟基壬烯醛（HNE）增加。该项目将汇集一群患有不同程度神经认知障碍的HIV阳性个体：1)在一组接受haart治疗的受试者中确定氧化应激标志物与HIV-D之间的关系，并确定这些标志物与巨噬细胞和星形胶质细胞活化的实验室标志物以及炎症和神经元损伤的神经影像学标志物之间的关系。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.