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

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要巴西寨卡病毒2016年的爆发发起了国际公共卫生危机，很明显在子宫内感染的婴儿天生患有毁灭性的神经缺陷。此外，令人不安的报告有表明许多被感染的婴儿出生时是“神经学正常”，但后来经历了非典型的经验发育和神经感觉改变为婴儿期。 Zika的长期发展后果目前未知感染，但其病理生物学的机制已与首选伤害有关轴突和髓鞘。早期的髓鞘形成中断或延迟，以前与重要相关以及跨感觉，运动和认知能力领域的永久损害。调查影响胎儿寨卡病毒感染在产后大脑发育中，这项研究将获得定量磁共振在6、12、24和30的已建立的非人类私有模型中髓磷脂和轴突成熟的成像指标几个月（在人类中等同于10岁左右）。因此，这项提议的工作通过跟踪整个大脑在体内的组织微观结构的变化，在大脑发育的加速模型中将这些变化与细胞解剖结构联系起来，Mortem。与轴突和髓磷脂损伤有关的行为结果也将进行调查。该提议的目的是直接翻译成人类研究的目的并将建立一个宝贵的资源来预测和解释胎儿寨卡病毒感染的结果。