Imaging neurotoxicity: The effect of anti-NMDAR Ab on hippocampus and amygdala in

项目3：影像神经毒性：抗NMDAR抗体对大鼠海马区和杏仁核的影响 NPSLE患者“(Hirsch，PI) 系统性红斑狼疮是一种自身免疫性疾病，以抗核抗体的存在为特征。 抗体，尤其是针对DNA的抗体。随着时间的推移，狼疮患者会出现认知障碍 和情绪障碍。我们已经确定了抗DNA抗体的一个子集，它与 NMDA受体(NMDAR)的NR2A和NR2B亚基。在小鼠身上，具有这种交叉反应的抗体 可导致海马区或杏仁核神经元的凋亡，导致认知能力下降 分别为损害或行为障碍。我们假设抗体与一种 血脑屏障的破坏，会损害狼疮患者的海马体和杏仁核， 随着时间的推移，打开血脑屏障的侮辱会积累起来。 该项目旨在评估功能磁共振成像(FMRI)是否是一种 灵敏的方式评估SLE患者的认知功能和情绪反应 与NMDAR交叉反应的抗DNA抗体的子集与损伤有关。我们 将使用功能磁共振成像来确定抗NMDAR抗体的患者是否会随着时间的推移而获得损害 为了评估海马体和杏仁核的活动，这两个区域服务于认知和情绪 记忆。建议进行两项研究：一项队列分析以确定抗体是否与 疾病10年或更长时间患者的损害，以及抗体是否与早期 疾病2年以下的患者的损害。第二项研究是纵向评估 以确定功能磁共振是否能在6个月的时间间隔内检测到变化。本研究是一项 系统性红斑狼疮神经保护临床试验的必要前提。

Project 3: "Imaging neurotoxicity: The effect of anti-NMDAR Ab on hippocampus and amygdala in NPSLE patients" (Hirsch, PI) Systemic lupus erythematosus is an autoimmune disease characterized by the presence of anti-nuclear antibodies, especially antibodies to DNA. Patients with lupus develop, over time, cognitive impairment and mood disorders. We have identified a subset of anti-DNA antibodies that cross-reacts with the NR2A and NR2B subunits of the NMDA receptor (NMDAR). In mice, antibodies with this crossreactivity can cause apoptosis of neurons in the hippocampus or the amygdala, leading to cognitive impairment or behavioral dysfunction, respectively. We hypothesize that antibody, together with a breach in the blood-brain barrier, can damage the hippocampus and amygdala in lupus patients, and that insults that open the blood-brain barrier accumulate over time. This project is designed to assess whether functional Magnetic Resonance Imagining (fMRI) is a sensitive modality to assess cognitive function and emotional response in patients with SLE and whether the subset of anti-DNA antibodies that cross-reacts with the NMDAR associates with impairment. We will determine whether patients with anti-NMDAR antibodies acquire impairment over time using fMRI to assess activity in the hippocampus and the amygdala, regions subserving cognition and emotional memory. Two studies are proposed: a cohort analysis to determine whether antibody associates with impairment in patients with disease for 10 or more years, and whether antibody associates with early impairment in patients with disease for less than 2 years. The second study is a longitudinal assessment of patients to determine if fMRI can detect change over a 6 month time interval. This study is a necessary precondition to a clinical trial of neuroprotection in SLE.