Neonatal dexamethasone treatment exacerbates hypoxic-ischemic brain injury

Kan Hsun Chang, Che Ming Yeh, Chia Yu Yeh, Chiung Chun Huang, Kuei Sen Hsu

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Background: The synthetic glucocorticoid dexamethasone (DEX) is commonly used to prevent chronic lung disease in prematurely born infants. Treatment regimens usually consist of high doses of DEX for several weeks, notably during a critical period of brain development. Therefore, there is some concern about adverse effects of this clinical practice on fetal brain development. In this study, using a clinically relevant rat model, we examined the impact of neonatal DEX treatment on subsequent brain injury due to an episode of cerebral hypoxia-ischemia (HI). Results: We found that a 3-day tapering course (0.5, 0.3 and 0.1 mg/kg) of DEX treatment in rat pups on postnatal days 1-3 (P1-3) exacerbated HI-induced brain injury on P7 by a glucocorticoid receptor-mediated mechanism. The aggravating effect of neonatal DEX treatment on HI-induced brain injury was correlated with decreased glutamate transporter-1 (GLT-1)-mediated glutamate reuptake. The expression levels of mRNA and protein of GLT-1 were significantly reduced by neonatal DEX treatment. We also found that the administration of β-lactam antibiotic ceftriaxone increased GLT-1 protein expression and significantly reduced HI-induced brain injury in neonatal DEX-treated rats. Conclusions: These results suggest that early DEX exposure may lead the neonatal brain to be more vulnerable to subsequent HI injury, which can be ameliorated by administrating ceftriaxone.

Original languageEnglish
Article number18
JournalMolecular brain
Volume6
Issue number1
DOIs
Publication statusPublished - 2013 Apr 22

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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