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Pediatr Res. 2015 May;77(5):618-24. doi: 10.1038/pr.2015.19. Epub 2015 Feb 9.

Dexamethasone but not the equivalent doses of hydrocortisone induces neurotoxicity in neonatal rat brain.

Author information

1
Department of Pediatrics, University of Mississippi Medical Center, Jackson, Mississippi.
2
Department of Pathology, University of Mississippi Medical Center, Jackson, Mississippi.

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.

PMID:
25665056
DOI:
10.1038/pr.2015.19
[Indexed for MEDLINE]

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