Longitudinal Characterization of Postnatal Brain Maturation after Fetal Zika Infection

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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.