title: Dexamethasone but not the equivalent doses of hydrocortisone induces neurotoxicity in neonatal rat brain.
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.
  
  
  CONCLUSIONS
  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.
authors: Department of Pediatrics, University of Mississippi Medical Center, Jackson, Mississippi.
authors: Yangzheng
authors: Y
authors: Feng
authors: Department of Pediatrics, University of Mississippi Medical Center, Jackson, Mississippi.
authors: Praveen
authors: P
authors: Kumar
authors: Department of Pathology, University of Mississippi Medical Center, Jackson, Mississippi.
authors: Junming
authors: J
authors: Wang
authors: Department of Pediatrics, University of Mississippi Medical Center, Jackson, Mississippi.
authors: Abhay J
authors: AJ
authors: Bhatt
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D053148:Caspase 3 / Q000378:metabolism; D003071:Cognition / Q000187:drug effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006854:Hydrocortisone / Q000008:administration & dosage / Q000009:adverse effects*; D007858:Learning / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D009048:Motor Skills / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000473:pathology; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003907:Dexamethasone; C505410:Casp3 protein, rat; D053148:Caspase 3; D006854:Hydrocortisone