Elsevier

Pediatric Neurology

Volume 53, Issue 3, September 2015, Pages 185-192
Pediatric Neurology

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

https://doi.org/10.1016/j.pediatrneurol.2015.04.006Get rights and content

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.

Section snippets

The changing spectrum of white matter injury in contemporary preterm survivors

In prior decades, preterm infants were at much higher risk for destructive brain lesions that resulted in cystic necrotic white matter injury (WMI) and secondary cortical and subcortical gray matter degeneration. Whereas cystic lesions were previously the major form of WMI in preterm survivors, the incidence has markedly declined.24, 25, 26, 27 In several recent series, focal cystic lesions were detected by magnetic resonance imaging (MRI) in fewer than 5% of patients.24, 25, 26, 27, 28, 29

Preterm survivors display impaired cerebral gray matter growth and function

Several large human neuroimaging studies have identified that preterm survivors display significant reductions in the growth of the cerebral cortex and subcortical gray matter structures that include the basal ganglia, thalamus, hippocampus, and cerebellum.50, 89, 90, 91, 92 Reduced cortical growth further manifests as varying degrees of abnormal cortical folding and reduced gyral complexity.93 As children and adults, preterm survivors with normal neurocognitive function nevertheless display

Conclusions

Advances in neonatal care have markedly reduced the overall severity of cerebral injury in infants born prematurely. At the more severe end of the spectrum are preterm survivors with major motor and cognitive disabilities related to destructive lesions where focal or more diffuse loss of neurons and glia occurs. For the majority of more mildly affected children, the burden of chronic disabilities may be related to a primary diffuse cerebral dysmaturation disorder that may respond to

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