Research Express@NCKU - Articles Digest
Research Express@NCKU Volume 27 Issue 4 - August 29, 2014 [ http://research.ncku.edu.tw/re/articles/e/20140829/3.html ]
Neonatal dexamethasone treatment exacerbates
hypoxic-ischemic brain injury
Kan-Hsun Chang, Che-Ming Yeh, Chia-Yu Yeh, Chiung-Chun Huang, Kuei-Sen Hsu
* Department of Pharmacology, College of Medicine, National Cheng Kung University [email protected]Molecular Brain 6:18 (2013).
T
he 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 braininjury due to an episode of cerebral hypoxia-ischemia (HI). We found that a 3-day tapering course 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. Our 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.
Research Express@NCKU - Articles Digest
Figure 1. Effect of neonatal DEX treatment on HI-induced brain injury.
These findings are of clinical importance because it is now difficult to avoid the use of corticosteroids in neonatology and perinatology to fight the problems of chronic lung disease.
