title: Neonatal dexamethasone treatment exacerbates hypoxic-ischemic brain injury.
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.
authors.affiliation: Department of Pharmacology, College of sMedicine, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Kan-Hsun
authors.initials: KH
authors.lastname: Chang
authors.forename: Che-Ming
authors.initials: CM
authors.lastname: Yeh
authors.forename: Chia-Yu
authors.initials: CY
authors.lastname: Yeh
authors.forename: Chiung-Chun
authors.initials: CC
authors.lastname: Huang
authors.forename: Kuei-Sen
authors.initials: KS
authors.lastname: Hsu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001930:Brain Injuries / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D002443:Ceftriaxone / Q000494:pharmacology; D045744:Cell Line, Tumor; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use*; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D020925:Hypoxia-Ischemia, Brain / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
chemical_list: D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D005971:Glutamates; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; C493396:Slc1a2 protein, mouse; C493393:Slc1a3 protein, mouse; D002443:Ceftriaxone; D003907:Dexamethasone