Longitudinal Characterization of Postnatal Brain Maturation after Fetal Zika Infection

项目总结 2016年巴西寨卡病毒爆发引发了一场国际公共卫生危机，当时很明显 在宫内感染的婴儿出生时就患有毁灭性的神经缺陷。此外，令人不安的报告还显示 结果显示，许多受感染的婴儿出生时神经学上是正常的，但后来出现了不典型的症状 婴儿期的发育和神经感觉变化。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被认为与优先损伤有关 轴突和髓鞘。早期生命中的髓鞘形成障碍或延迟以前与显著的 以及感觉、运动和认知能力等领域的永久性损伤。调查其影响 胎儿寨卡病毒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 建立的非人灵长类动物模型在6、12、24和30岁时髓鞘和轴突成熟的成像指标 年龄的月份(相当于人类10岁以下)。因此，这项拟议的工作采取了一种新颖的方法，即 在一个大脑发育和发育加速模型中，在活体内跟踪整个大脑组织微结构的变化 将这些变化与尸检后的细胞解剖联系起来。与轴突和髓鞘损伤相关的行为结局 也将接受调查。这项提议的目的是为了直接翻译成人体研究 并将为预测和解释胎儿寨卡病毒感染的结果建立有价值的资源。

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.