The Near-Term (Late Preterm) Human Brain and Risk for Periventricular Leukomalacia: A Review
Section snippets
Brain Development and Injury in the Late Preterm Infant
The last half of gestation is a critical period in the growth and development of the human brain (Figure 1, Figure 2, Figure 3). A “critical period” is defined as a time-sensitive, irreversible “decision point” in the development of a neural structure or system in which deprivation of the normal environment interrupts the maturational trajectory of the structure/system. As a result, there are profound consequences for later brain maturation and behavior that cannot be corrected. Critical brain
Definition of PVL
PVL is defined morphologically by two histopathologic components: (1) a “focal”, necrotic component in the periventricular region of the cerebral white matter; and (2) a “diffuse” component characterized by reactive gliosis in the surrounding white matter.5 Each component has different histopathologic outcomes: (1) the necrotic foci, involving all tissue components, evolve into cysts that typically collapse and eventually form focal scars; and (2) the diffuse lesion appears to involve
Incidence of PVL in Late Preterm and Term Infants
The incidence of PVL in preterm and term infants is not completely known. In our study of the neuropathology of congenital heart disease in infants dying after cardiopulmonary bypass surgery (n = 38), the mean gestational age was 39.3 ± 1.4 weeks (term), with a mean birth weight of 3126 ± 53 g and median postnatal age of 21 days (range: 1-398 days).7 In this cohort, the overall incidence of PVL was 61%, with this lesion representing the most common neuropathologic finding.7 Of note, 32% of the
Pathogenesis of PVL
The major causes of PVL are considered to be: (1) cerebral ischemia/reperfusion in the critically ill premature infant with cerebral vascular immaturity and arterial end-zones in the periventricular region, coupled with the propensity for impaired vascular autoregulation; and (2) bacterial infection in the mother and/or fetus that triggers a cytokine response in the fetal brain, either by entry of maternal and/or fetal cytokines across the fetal blood–brain–barrier that then directly injure
Maturational Factors of the Cerebral White Matter in the Late Preterm Infant
A major focus of our laboratory has been to determine the developmental factors at the cellular level that underlie the vulnerability of the fetal white matter to injury in PVL. The first step we took in our laboratory toward understanding these factors was to delineate the developmental profile of OL cell lineage during the peak period of risk (Fig. 4).14 In 26 control autopsy brains, OL lineage progression was defined by us in the parietal white matter at the level of the atrium, a known
Summary
In summary, different events in cerebral white and gray matter development, eg, OL differentiation, myelination, antioxidant enzyme production, gyration, synaptogenesis, and axonal elongation, follow different sequences of maturation with different tempos in the human brain over the last half of gestation, thereby defining differential periods of vulnerability to injury. The maturation of the cerebral white matter is incomplete in the late preterm brain, and thus it is vulnerable to PVL, as
Acknowledgments
The author appreciates the assistance of Mr. Richard A. Belliveau in manuscript preparation, and of Drs. Robin L. Haynes and Joseph J. Volpe in critical reading of the manuscript. This work is supported by the National Institute of Neurological Disorders and Stroke (PO1-NS38475) and Children’s Hospital Boston Mental Retardation Research Center (P01-HD18655).
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