Patterns of Cerebral Injury in a Primate Model of Preterm Birth and Neonatal Intensive Care

Abstract

Very preterm birth is associated with significant neurodevelopmental morbidity, with 10% to 15% of these infants later developing cerebral palsy and up to 50% experiencing learning disabilities. The nature of the cerebral lesion predisposing these infants to such impairments is not fully understood but is likely related to both cerebral injury and alterations in cerebral development associated with neonatal intensive care. To study the impact of both preterm birth and neonatal intensive care on the immature brain, we are studying a preterm primate model delivered at 125 days of a 184-day gestational period and cared for in a neonatal intensive care unit for 2 to 4 weeks in a fashion highly similar to that for human preterm infants. The most common neuropathology in this model is white-matter damage manifested by reactive astrogliosis or activated microglia and enlarged ventricular size. Subarachnoid, germinal matrix, and intraventricular hemorrhages are also common. These preliminary results support the similarity of this model to both the alterations in cerebral developmental and the pattern of cerebral injury found in human preterm infants. We are now investigating the impact of randomized respiratory therapies on the pattern of cerebral injury. The prematurely born baboon appears to be an accurate and relevant model for the study of preterm human birth.