Abstract
Background:
The use of dexamethasone (Dex) in premature infants to treat or prevent chronic lung disease adversely affects neurodevelopment. Recent clinical studies suggest that hydrocortisone (HC) is a safer alternative to Dex. We compared the effects of Dex and HC on neurotoxicity in newborn rats.
Methods:
Rat pups of a neurodevelopmental stage equivalent to premature human neonates were administered Dex or HC either as a single dose on postnatal day (PD) 6, repeated doses on PD 4 to 6 or tapering doses at PD 3 to 6 by i.p. injection. Brain weight, caspase-3 activity, and apoptotic cells were measured at PD 7; learning capability, memory, and motor function were measured at juvenile age.
Results:
Dex decreased both body and brain weight gain, while HC did not. Tapering and repeated doses of Dex increased caspase-3 activity, cleaved caspase-3 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells but HC, except at high doses, did not. Dex impaired learning and memory capability at juvenile age, while the rats exposed to HC showed normal cognitive behavior.
Conclusion:
HC is probably safer to use than Dex in the immediate postnatal period in neonatal rats. Cautious extrapolation of these findings to human premature infants is required.
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We thank Nicole Burton for the admirable English editorial assistance.
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Feng, Y., Kumar, P., Wang, J. et al. Dexamethasone but not the equivalent doses of hydrocortisone induces neurotoxicity in neonatal rat brain. Pediatr Res 77, 618–624 (2015). https://doi.org/10.1038/pr.2015.19
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DOI: https://doi.org/10.1038/pr.2015.19
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