Brain Injury in the Preterm Infant: New Horizons for Pathogenesis and Prevention

Abstract Preterm neonates are surviving with a milder spectrum of motor and cognitive disabilities that appear to be related to widespread disturbances in cell maturation that target cerebral gray and white matter. Whereas the preterm brain was previously at high risk for destructive lesions, preterm survivors now commonly display less severe injury that is associated with aberrant regeneration and repair responses that result in reduced cerebral growth. Impaired cerebral white matter growth is related to myelination disturbances that are initiated by acute death of premyelinating oligodendrocytes, but are followed by rapid regeneration of premyelinating oligodendrocytes that fail to normally mature to myelinating cells. Although immature neurons are more resistant to cell death than mature neurons, they display widespread disturbances in maturation of their dendritic arbors and synapses, which further contributes to impaired cerebral growth. Thus, even more mild cerebral injury involves disrupted repair mechanisms in which neurons and premyelinating oligodendrocytes fail to fully mature during a critical window in development of neural circuitry. These recently recognized distinct forms of cerebral gray and white matter dysmaturation raise new diagnostic challenges and suggest new therapeutic strategies to promote brain growth and repair.