Cerebral white and gray matter injury in newborns: new insights into pathophysiology and management.

Increasing numbers of preterm neonates survive with motor and cognitive disabilities related to less destructive forms of cerebral injury that still result in reduced cerebral growth. White matter injury results in myelination disturbances related to aberrant responses to death of pre-myelinating oligodendrocytes (preOLs). PreOLs are rapidly regenerated but fail to mature to myelinating cells. Although immature projection neurons are more resistant to hypoxia-ischemia than preOLs, they display widespread disturbances in dendritic arbor maturation, which provides an explanation for impaired cerebral growth. Thus, large numbers of cells fail to fully mature during a critical window in development of neural circuitry. These recently recognized forms of cerebral gray and white matter dysmaturation suggest new therapeutic directions centered on reversal of the processes that promote dysmaturation.