Longitudinal Characterization of Postnatal Brain Maturation after Fetal Zika Infection

胎儿寨卡病毒感染后产后大脑成熟的纵向特征

• 批准号: 10297831
• 负责人: Erika Pratt Raven
• 金额: $ 6.81万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10297831
• 关键词: 5 year old; 8 year old; Affect; Age; Age-Months; Animal Model; Animals; Auditory; Axon; Behavior; Behavioral; Birth; Brain; Brain region; Cell physiology; Cells; Cerebrum; Child; Clinical; Consensus; Data; Defect; Development; Diagnostic; Diffusion Magnetic Resonance Imaging; Disease; Disease Outbreaks; Early Diagnosis; Epidemic; Event; Exhibits; Fellowship; Female; Goals; Histologic; Histology; Human; Image; Image Analysis; Impairment; In Vitro; Individual; Infant; Infection; Injury; International; Life; Link; Macaca; Macaca mulatta; Magnetic Resonance Imaging; Measurement; Measures; Microcephaly; Microscopy; Modeling; Monitor; Monkeys; Motor; Myelin; Myelin Sheath; Neurodevelopmental Deficit; Neurologic; Oligodendroglia; Outcome; Pathology; Phenotype; Pregnancy; Primates; Public Health; Publications; Reporting; Research; Resolution; Resources; Rodent Model; Sensory; Speed; Stereotyping; Structure; Subcellular Anatomy; Techniques; Testing; Time; Tissues; Toddler; Training; Validation; Work; ZIKA; ZIKV infection; Zika Virus; autism spectrum disorder; axon injury; base; behavioral outcome; career; cellular pathology; clinically relevant; cognitive ability; cognitive function; design; early childhood; experience; fetal; imaging biomarker; in utero; in vivo; infancy; innovation; male; myelination; neurodevelopment; neuroimaging; neurosensory; nonhuman primate; novel strategies; outcome prediction; postnatal; spatiotemporal; support network; tool; translation to humans; treatment effect; visual motor; white matter

PROJECT SUMMARY The Brazilian Zika virus outbreak of 2016 initiated an international public health crisis when it became clear that babies infected in utero were being born with devastating neurological defects. In addition, troubling reports have shown that many infected babies present as “neurologically-normal” at birth but experience later atypical developmental and neurosensory alterations into infancy. The long-term developmental consequences of Zika infection are currently unknown, but mechanisms of its pathobiology have been linked to the preferential injury of axons and myelin. Disrupted or delayed myelination in early life has been previously associated to significant and permanent impairments across domains of sensory, motor, and cognitive abilities. To investigate the impact of fetal Zika infection on postnatal brain development, this study will acquire quantitative magnetic resonance imaging metrics of myelin and axon maturation in an established nonhuman primate model at 6, 12, 24, and 30 months of age (equivalent up to ~ age 10 in humans). This proposed work, therefore, takes a novel approach by tracking whole brain changes in tissue microstructure, in vivo, in an accelerated model of brain development and links those changes to cellular anatomy, post mortem. Behavioral outcomes related to axon and myelin injury will also be investigated. The aims of this proposal have been designed for direct translation to human studies and will establish a valuable resource for predicting and interpreting outcomes of fetal Zika infection.

项目摘要 2016年巴西寨卡病毒爆发引发了一场国际公共卫生危机，当时人们清楚地认识到， 子宫内感染的婴儿出生时就有严重的神经缺陷。此外，令人不安的报告 显示许多受感染的婴儿在出生时表现为“神经学正常”，但后来经历了非典型性， 发育和神经感觉的改变。寨卡病毒的长期发展后果 感染目前尚不清楚，但其病理生物学机制已与优先损伤有关。 轴突和髓磷脂。早期髓鞘形成中断或延迟以前与显著的 以及感觉、运动和认知能力领域的永久性损伤。调查的影响 胎儿寨卡感染对出生后大脑发育的影响，这项研究将获得定量磁共振成像， 在6、12、24和30岁时建立的非人灵长类动物模型中髓鞘和轴突成熟的成像指标 月龄（相当于人类约10岁）。因此，这项拟议的工作采取了一种新颖的方法， 在大脑发育的加速模型中，在体内跟踪组织微观结构的全脑变化， 将这些变化与死后的细胞结构联系起来与轴突和髓鞘损伤相关的行为结局 也将被调查。本提案的目的旨在直接转化为人类研究 并将为预测和解释胎儿寨卡病毒感染的结果建立一个有价值的资源。