Anoxia ameliorates the dexamethasone-induced neurobehavioral alterations in the neonatal male rat pups

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Abstract

Glucocorticoids and hypoxia are two essential factors affecting the brain development during labor and delivery. In addition to the neurobehavioral alterations induced separately by these factors, glucocorticoids can attenuate the deleterious consequences of severe hypoxia-ischemia on the brain development, acting as a neuroprotective agent in combination with hypoxia. The role of hypoxia in the combined action with corticosteroids is less clear. Severe hypoxia-ischemia results in the massive activation of caspase-3, masking any other effects of hypoxia on the neonatal brain exposed to glucocorticoids. As a result, the effects of mild hypoxia on the developing brain pretreated with glucocorticoids remain unclear. To analyze this problem, 2-day-old male rats were treated with dexamethasone (DEX) before the subsequent exposure to mild 10-min anoxia or normoxia. The treatment with only DEX resulted in the delay in the development of the negative geotaxis reaction and in the decrease in locomotor activity of the neonatal male pups. The mild anoxic event attenuated these DEX-induced neurobehavioral alterations. The treatment with DEX, but not the mild anoxic exposure alone, resulted in the delayed upregulation of active caspase-3 in the prefrontal cortex and in the brainstem of the male pups. This glucocorticoid-induced upregulation of active caspase-3 was prevented by the anoxic event. The present findings evidence that mild anoxia is capable of ameliorating the glucocorticoid-induced neurodevelopmental alterations in the neonatal rats if the artificial or the naturally occurring increase in the levels of glucocorticoids occurred just before the episode of hypoxia.

Original languageEnglish
Pages (from-to)122-128
Number of pages7
JournalHormones and Behavior
Volume87
DOIs
Publication statusPublished - 1 Jan 2017

Keywords

  • Anoxia
  • Brain
  • Brainstem
  • Caspase-3
  • Cortex
  • Development
  • Dexamethasone
  • Glucocorticoids
  • Hypoxia
  • Perinatal
  • Animals, Newborn
  • Up-Regulation/drug effects
  • Neuroprotection
  • Rats, Wistar
  • Locomotion/drug effects
  • Rats
  • Male
  • Glucocorticoids/adverse effects
  • Brain/drug effects
  • Prefrontal Cortex/drug effects
  • Animals
  • Behavior, Animal/drug effects
  • Hypoxia/physiopathology
  • Dexamethasone/adverse effects
  • APOPTOSIS
  • ENVIRONMENT
  • HYPOXIA
  • HIPPOCAMPUS
  • ACTIVE CASPASE-3
  • ISCHEMIC BRAIN-DAMAGE
  • LABOR
  • CEREBELLAR
  • HYDROCORTISONE
  • EXPRESSION

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