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

Abstract

Survivors of very premature birth face an increased risk of adverse motor, cognitive, and behavior sequelae. In order to understand the pathogenesis of these adverse outcomes, an animal model of premature birth and neonatal care in a species with a close similarity to the human infant is sought. In this histological and immunohistochemical study we have defined the pattern of cerebral injury in a premature baboon model undergoing similar neonatal intensive care to that of the human premature infant. Sixteen baboons were delivered at 125 days gestation (dg; term approximately184 dg) with 14 days neonatal intensive care and were compared with gestational control brains at 125, 140, and 160 dg. The premature baboons undergoing neonatal intensive care sustained a spectrum of neuropathologies including white matter injury, hemorrhage, and ventriculomegaly, which resemble lesions frequently observed in the human premature infant. These data suggest that the premature baboon is a model with similarities in maturation and pattern of cerebral injury to the human infant that may provide useful insights of relevance to the human preterm infant.

Microstructural Changes of the Baboon Cerebral Cortex during Gestational Development Reflected in Magnetic Resonance Imaging Diffusion Anisotropy

“…Five additional brains (not included in the MRI analysis) were processed histologically. Procedures for sectioning into 5-mm-thick coronal blocks, paraffin embedding, slicing, and hematoxylin and eosin (H&E), staining have been published previously for brains of 125, 140, and 160 d gestation (Dieni et al, 2004). Two additional brains of 90 and 185 d gestation were processed using identical procedures.…”

“…Two additional brains of 90 and 185 d gestation were processed using identical procedures. Cortical thickness was estimated for each of the 5 brains (Dieni et al, 2004). Cortical thickness at other ages (e.g., E146 and E175) was estimated by linear interpolation between the two closest, age-matched younger and older brains.…”

“…Independent estimates of the cortical thickness at ϳ15 places throughout the isocortex (depending on the size of the brain) at multiple stages of gestation were made from H&E stained material (Dieni et al, 2004). H&E stained sections from the superior parietal lobe are shown in Figure 4b.…”

“…The human RA was 0.27 of the baboon peak RA. The abscissa of the plot in Figure 4c relates cortical anisotropy changes as the percentage of a 40 week human gestation, assuming equivalence between a 160 d gestation baboon and a term human (Dieni et al, 2004).…”

Animal models of bronchopulmonary dysplasia. The preterm baboon models

“…Specifically, we have reported an ontogeny of cerebral development similar to the human that shows abnormalities in postnatal growth and evidence for white and gray matter injury associated with neonatal intensive care, but not specific interventional therapies (25,44,62,64). More importantly, this model first demonstrated the neurological impact of mechanical ventilation on the preterm brain and the relative sparing effect of early noninvasive respiratory support (43,63,85).…”