Preterm Delivery Disrupts the Developmental Program of the Cerebellum

Abstract

A rapid growth in human cerebellar development occurs in the third trimester, which is impeded by preterm delivery. The goal of this study was to characterize the impact of preterm delivery on the developmental program of the human cerebellum. Still born infants, which meant that all development up to that age had taken place in-utero, were age paired with preterm delivery infants, who had survived in an ex-utero environment, which meant that their development had also taken place outside the uterus. The two groups were assessed on quantitative measures that included molecular markers of granule neuron, purkinje neuron and bergmann glia differentiation, as well as the expression of the sonic hedgehog signaling pathway, that is important for cerebellar growth. We report that premature birth and development in an ex-utero environment leads to a significant decrease in the thickness and an increase in the packing density of the cells within the external granular layer and the inner granular layer well, as a reduction in the density of bergmann glial fibres. In addition, this also leads to a reduced expression of sonic hedgehog in the purkinje layer. We conclude that the developmental program of the cerebellum is specifically modified by events that follow preterm delivery.

Intrauterine Growth Restriction Alters the Postnatal Development of the Rat Cerebellum

“…Hypoxia and undernutrition, both of which occur during IUGR have also been shown to affect Bergmann glia development [40,41] , suggesting that these factors may mediate the effect of IUGR on Bergmann glial fibers. Similarly, babies that are born preterm also have decreased Bergmann glial fiber density and fibers that do not extend to the pial surface of the cerebellum [42] . Taken together, this suggests that Bergmann glia are particularly vulnerable to insults in the perinatal period, including IUGR.…”

Preterm cerebellum at term age: ultrasound measurements are not different from infants born at term

“…We suggest cUS can be used to assess cerebellar size at TEA, with measures of both width and height being taken into account, and thus may be a useful tool for detecting infants with poorer cerebellar growth who are at increased risk of disability. a n extrauterine environment is adverse for brain development of preterm infants (1)(2)(3). Survival of very preterm infants and survival without neurodevelopmental disabilities have improved (4) with better outcomes for very immature infants born in the last decade as compared with those born in the 1990s (5).…”

Brain Injury in Preterm Infants: Pathogenesis and Nursing Implications

“…1,6 Neuronal migration in the cerebral cortex is generally complete by about 5 month's gestation; neuronal migration in the cerebellum (which contains its own germinal matrix) continues into the postnatal period. 12,13 Glial cell migration continues into the eighth month.…”

“…1,4 Diffuse PVL is characterized by damage to pre-myelinating oligodendrocytes (pre-OL) leading to hypomyelination, astrocystosis and microgliosis. 4,12,13 Diffuse white matter injury involves primarily astrocytes, microglia and degeneration of pre-OLs and leads to failure of myelination. 4 In recent years studies have reported a shift from the more destructive cystic lesions to less severe chronic injury from the diffuse form (which are still associated with decreased cerebral growth and altered neurodevelopmental…”