Imaging neuroglial mechanisms of neuropathic pain-opioid interaction in HIV

项目摘要/摘要 自2020年3月世界卫生组织宣布新冠肺炎大流行以来，越来越多的证据表明 研究表明，新冠肺炎影响多个器官，包括中枢神经系统。冠状病毒病的影响- 通过磁共振成像(MRI)在住院环境中很好地记录了CNS上的19例 和波谱(MRS)、血液和脑脊液生物标记物和尸检。神经学问题 与新冠肺炎相关的疾病可以持续很久，从新冠肺炎的初期阶段恢复过来，包括疲劳， 新冠肺炎幸存者报告的前十大症状包括认知迟钝和身体疼痛。 根据疾病控制中心的说法，艾滋病毒携带者(PWH)可能面临更高的严重后果风险 来自新冠肺炎，该人群的长期神经后遗症尚不清楚，可能代表着一种 临床表型面临未来健康威胁的风险(即，认知障碍的发展)。数据通知 新冠肺炎长期症状的潜在生物学是有限的，以及新冠肺炎和艾滋病毒可能如何相互作用 影响神经功能是当务之急。根据新冠肺炎的临床表现，并发症 从轻度到重度，以及已知的脑病理触发因素、神经炎症(目标1)和 神经元完整性(AIM 2)被认为是COVID急性后遗症(PASC)的重要组成部分。 为了评估PASC患者的神经胶质细胞失调，我们将使用先进的脑成像技术， 神经心理测试、疲劳测量和定量感觉测试(QST)。具体来说， 集成[11C]PBR28正电子发射断层扫描/磁共振(PET/MR)和3-特斯拉质子 磁共振波谱(1HMRS)将被用来评估大脑中胶质标志物(18 KDa)的水平 转位蛋白、TSPO和肌醇，以及神经元/结构完整性标记(N- 乙酰天冬氨酸(NAA)。QST技术将评估痛阈值、阈值上的敏感度和时间 总结，而认知功能将使用详细的神经心理学组件进行评估 对新冠肺炎患者的注意力和注意力进行评估。有持续性神经症状的人在 新冠肺炎将报名参加这一补充奖项。父R01将提供两个比较器控制 人群包括以前没有感染新冠肺炎的艾滋病毒携带者和非艾滋病毒携带者。集团化 神经炎症和神经元完整性的磁共振标志物的差异及其相关性 有包括认知功能和疼痛在内的神经症状的患者将接受调查。机械的洞察力 由这项补充研究提供的艾滋病毒-新冠肺炎相互作用将告知护理和神经科 对包括威尔斯亲王在内的新冠肺炎患者的管理，预计他们将长期遭受 未来几年大流行的后果。

PROJECT SUMMARY/ABSTRACT Since the World Health Organization declared COVID-19 a pandemic in March 2020, increasing evidence shows that COVID-19 affects multiple organs, including the central nervous system (CNS). Effects of COVID- 19 on the CNS have been well documented in the hospitalized setting by magnetic resonance imaging (MRI) and spectroscopy (MRS), blood and cerebrospinal fluid biomarkers and autopsy. Neurological problems associated with COVID-19 can persist long past recovery from the initial stages of COVID-19, including fatigue, cognitive blunting, and body pain which are among the top 10 symptoms reported by COVID-19 survivors. According to the Center for Disease Control, people with HIV (PWH) may be at higher risk for severe outcomes from COVID-19, and the long-term neurological sequelae in this population is unknown and may represent a clinical phenotype at risk for future health threats (i.e., development of cognitive disorders). Data informing the underlying biology of prolonged symptoms in COVID-19 is limited, and how COVID-19 and HIV may interact to affect neurological function is urgently needed. Based on the clinical presentation of COVID-19, complications ranging from mild-to-severe, and known triggers of cerebral pathology, neuroinflammation (Aim 1) and loss of neuronal integrity (Aim 2) are expected to be important components of post-acute sequalae of COVID (PASC). To evaluate neuro-glial dysregulation in people with PASC, we will use advanced brain imaging technologies, neuropsychological testing, fatigue measurements and quantitative sensory testing (QST). Specifically, integrated [11C]PBR28 Positron Emission Tomography / Magnetic Resonance (PET/MR) and 3-Tesla proton magnetic resonance spectroscopy (1H MRS) will be used to evaluate brain levels of glial markers (18kDa translocator protein, TSPO, and myo-inositol, mI), and neuronal / structural integrity markers (N- acetylaspartate, NAA). QST techniques will assess pain threshold, suprathreshold sensitivity and temporal summation, while cognitive function will be assessed using detailed neuropsychological battery designed for COVID-19 patients to assess concentration and attention. People with persistent neurological symptoms after COVID-19 will be enrolled for this supplemental award. The parent R01 will provide two comparator control populations that include people with and without HIV who were not previously infected with COVID-19. Group differences in magnetic resonance markers of neuroinflammation and neuronal integrity and their associations with neurological symptoms including cognitive function and pain will be investigated. The mechanistic insights provided by this supplemental study in HIV-COVID-19 interaction will inform the care and neurological management of people with COVID-19, including PWH, and who are expected to suffer long-term consequences of the pandemic for years to come.