Imaging neuroglial mechanisms of neuropathic pain-opioid interaction in HIV

HIV中神经性疼痛与阿片类药物相互作用的神经胶质细胞成像机制

• 批准号: 10553020
• 负责人: Marco Luciano Loggia
• 金额: $ 118.65万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10553020
• 关键词: Acute; Affect; Anterior; Antibodies; Attention; Autopsy; Award; Biochemical; Biological; Biological Markers; Biology; Blood; Brain; Brain imaging; COVID-19; COVID-19 complications; COVID-19 impact; COVID-19 patient; COVID-19 survivors; Caring; Centers for Disease Control and Prevention (U.S.); Cerebrospinal Fluid; Cerebrum; Clinical; Cognition Disorders; Cognitive; Data; Demyelinations; Diffusion; Disease; Dorsal; Enrollment; Fatigue; Functional disorder; Future; Goals; HIV; Health; Image; Imaging technology; Impaired cognition; Individual; Infection; Inflammatory; Inositol; Insula of Reil; Leukoencephalopathy; Location; Long COVID; Magnetic Resonance; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measurement; Measures; N-acetylaspartate; Nerve Degeneration; Nervous System Physiology; Neuraxis; Neurologic; Neurologic Symptoms; Neurological Models; Neurons; Neuropsychological Tests; Neuropsychology; Opioid; Organ; Outcome; Pain; Pain Threshold; Parents; Participant; Pathologic; Pathology; Patients; Pattern; Persons; Phase; Population; Population Control; Positron-Emission Tomography; Post-Acute Sequelae of SARS-CoV-2 Infection; Prefrontal Cortex; Proteins; Protons; Recovery; Reporting; Research; Risk; Role; SARS-CoV-2 infection; Sensory; Severities; Site; Spectrum Analysis; Symptoms; Syndrome; Techniques; Testing; Thalamic structure; Time; Underrepresented Minority; Viral; Virus Diseases; White Matter Disease; World Health Organization; antiretroviral therapy; associated symptom; astrogliosis; base; chemokine; cingulate cortex; clinical phenotype; cognitive development; cognitive function; cognitive testing; cohort; coronavirus disease; cytokine; design; disability; experience; glial activation; high risk; hypoxic ischemic injury; insight; interest; long term consequences of COVID-19; magnetic field; marginalized community; multimodality; myoinositol; neurobiological mechanism; neuroinflammation; neuron loss; painful neuropathy; pandemic disease; post SARS-CoV-2 infection; post-COVID-19; spectroscopic imaging; therapy development

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.

项目总结/摘要 自世界卫生组织于2020年3月宣布COVID-19为大流行以来，越来越多的证据表明， 显示COVID-19影响多个器官，包括中枢神经系统（CNS）。COVID的影响- 19例CNS疾病已在住院期间通过磁共振成像（MRI）得到充分证实 和波谱学（MRS）、血液和脑脊液生物标志物和尸检。神经问题 与COVID-19相关的疾病可以在COVID-19初始阶段恢复后很长时间内持续存在，包括疲劳， 认知迟钝和身体疼痛是COVID-19幸存者报告的十大症状之一。 根据疾病控制中心的说法，艾滋病毒感染者（PWH）可能面临更高的严重后果风险。 从COVID-19，和长期的神经系统后遗症，在这一人群是未知的，可能代表了一个 具有未来健康威胁风险的临床表型（即，认知障碍的发展）。数据通知 COVID-19长期症状的潜在生物学是有限的，以及COVID-19和HIV如何相互作用， 影响神经功能是迫切需要的。根据COVID-19的临床表现， 范围从轻度到重度，以及已知的脑病理学、神经炎症（目的1）和 神经元完整性（目标2）预期是COVID急性后后遗症（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， 神经心理学测试、疲劳测量和定量感觉测试（QST）。具体地说， 集成[11 C] PBR 28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）将用于评估脑胶质细胞标记物（18 kDa）的水平 转运蛋白，TSPO，和肌醇，mI），和神经元/结构完整性标志物（N- 乙酰天冬氨酸，NAA）。QST技术将评估疼痛阈值、阈上敏感性和时间敏感性。 总结，而认知功能将使用详细的神经心理电池进行评估， 评估COVID-19患者的专注度和注意力。患有持续性神经症状的人， COVID-19将参加此补充奖励。父代R 01将提供两个对照品 包括先前未感染COVID-19的艾滋病毒感染者和非艾滋病毒感染者。组 神经炎症和神经元完整性磁共振标记物的差异及其相关性 将研究神经系统症状，包括认知功能和疼痛。机械论的观点 这项补充研究提供的艾滋病毒-COVID-19相互作用将告知护理和神经系统 管理感染COVID-19的人士，包括威尔斯亲王医院，以及预期会长期受影响的人士。 这一流行病的后果将在未来几年内持续下去。

项目成果

Transcriptional and cellular signatures of cortical morphometric remodelling in chronic pain.

• DOI: 10.1097/j.pain.0000000000002480
• 发表时间: 2022-06-01
• 期刊: Pain
• 影响因子: 7.4
• 作者: Martins D;Dipasquale O;Veronese M;Turkheimer F;Loggia ML;McMahon S;Howard MA;Williams SCR
• 通讯作者: Williams SCR

Cognitive concerns are a risk factor for mortality in people with HIV and coronavirus disease 2019.

• DOI: 10.1097/qad.0000000000003595
• 发表时间: 2023-08-01
• 期刊: AIDS (London, England)

Neuroinflammation in post-acute sequelae of COVID-19 (PASC) as assessed by [11C]PBR28 PET correlates with vascular disease measures.

通过 [11C]PBR28 PET 评估，COVID-19 (PASC) 急性后遗症中的神经炎症与血管疾病指标相关。

• DOI: 10.1101/2023.10.19.563117
• 发表时间: 2023
• 期刊: bioRxiv : the preprint server for biology
• 作者: VanElzakker,MichaelB;Bues,HannahF;Brusaferri,Ludovica;Kim,Minhae;Saadi,Deena;Ratai,Eva-Maria;Dougherty,DarinD;Loggia,MarcoL
• 通讯作者: Loggia,MarcoL

The pandemic brain: Neuroinflammation in non-infected individuals during the COVID-19 pandemic.

大脑大脑：在Covid-19大流行期间未感染个体的神经炎症。

• DOI: 10.1016/j.bbi.2022.02.018
• 发表时间: 2022-05
• 期刊: Brain, behavior, and immunity
• 作者: Brusaferri L;Alshelh Z;Martins D;Kim M;Weerasekera A;Housman H;Morrissey EJ;Knight PC;Castro-Blanco KA;Albrecht DS;Tseng CE;Zürcher NR;Ratai EM;Akeju O;Makary MM;Catana C;Mercaldo ND;Hadjikhani N;Veronese M;Turkheimer F;Rosen BR;Hooker JM;Loggia ML
• 通讯作者: Loggia ML

Thalamic neurometabolite alterations in chronic low back pain: a common phenomenon across musculoskeletal pain conditions?

• DOI: 10.1097/j.pain.0000000000003002
• 发表时间: 2024-01-01
• 期刊: PAIN
• 影响因子: 7.4
• 作者: Weerasekera，Akila;Knight，Paulina C.;Loggia，Marco L.
• 通讯作者: Loggia，Marco L.