Repeated prenatal corticosteroid administration delays myelination of the corpus callosum in fetal sheep

W.L. Huang, C.G. Harper, S.F. Evans, John Newnham, Sarah Dunlop

Research output: Contribution to journalArticlepeer-review

118 Citations (Scopus)

Abstract

Glucocorticoids regulate oligodendrocyte maturation and the myelin biosynthetic pathways. Synthetic glucocorticoids, the corticosteroids have been successfully used in clinical practice as a single course to enhance lung maturation and reduce mortality and morbidity in preterm infants with no long-term neurologic or cognitive side effects. However, a trend has arisen to use repeated courses despite an absence of safety data from clinical trials. We examined the effects of clinically appropriate, maternally administrated, repeated courses of corticosteroids on myelination of the corpus callosum using sheep as a large animal model. The corpus callosum is a major white matter tract that undergoes protracted myelination, underpins higher order cognitive processing and developmental damage to which is: associated with, for example, cerebral palsy, mental retardation and attention deficit hyperactivity disorder. Pregnant ewes were given saline or betamethasone (0.5 mg/kg) at 104, 111, 118 and 124 days gestation, stages equivalent to the third trimester in humans. Lambs were delivered at 145 days (term). perfused and the corpus callosum examined light and electron microscopically. Total axon numbers were unaffected (P >0.05). However, myelination was significantly delayed. Myelinated axons were 5.7% in the experimental group and 9.2% in controls (P <0.05); conversely, unmyelinated axons were 88.3 and 83.7% (P <0.05). Myelinated axon diameter and myelin sheath thickness were also reduced (0.68 vs. 0.94 and 0.11 vs. 0.14 mum, P <0.05). Our data suggest that repeated prenatal corticosteroid administration delays myelination of the corpus callosum and that further safety data are needed to evaluate clinical practice. 2001 ISDN. Published by Elsevier Science Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)415-425
JournalInternational Journal of Developmental Neuroscience
Volume19
DOIs
Publication statusPublished - 2001

Fingerprint

Dive into the research topics of 'Repeated prenatal corticosteroid administration delays myelination of the corpus callosum in fetal sheep'. Together they form a unique fingerprint.

Cite this