title: Neonatal Dexamethasone Treatment Exacerbates Hypoxia/Ischemia-Induced White Matter Injury.
abstract: Dexamethasone, a synthetic glucocorticoid, has been widely used to prevent or ameliorate morbidity of chronic lung disease in preterm infants with respiratory distress syndrome. Despite its beneficial effect on neonatal lung function, growing concern has arisen about adverse effects of this clinical practice on fetal brain development. We demonstrated previously that neonatal dexamethasone (DEX) treatment may render the newborn brain to be more vulnerable to hypoxia/ischemia (HI)-induced gray matter injury. Here, we examined whether neonatal DEX treatment may also affect the extent of HI-induced subcortical white matter (WM) injury in the developing rat brain. Using a HI model of premature brain injury, we demonstrated 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) significantly reduced the number of all stages of the oligodendroglial lineage cells on P7 and exacerbated HI-induced WM injury. Neonatal DEX treatment also enhanced HI-induced oligodendroglial apoptosis and astrocyte activation in the developing WM on P14. Likewise, HI-induced reductions in myelin thickness, axon caliber, and function during WM development were exacerbated by neonatal DEX treatment. Furthermore, neonatal DEX treatment further aggravated HI-induced motor deficits as assessed in the rotarod test. We also found that the administration of β-lactam antibiotic ceftriaxone increased glutamate transporter-1 protein expression and significantly reduced HI-induced WM injury in neonatal DEX-treated rats. These results suggest that neonatal DEX treatment may lead the developing brain to be more vulnerable to subsequent HI-induced WM injury, which can be ameliorated by ceftriaxone administration.
authors: Department of Pharmacology, College of Medicine, National Cheng Kung University, No. 1, University Rd, Tainan, 701, Taiwan.
authors: Chia -Yu
authors: C-
authors: Yeh
authors: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan.
authors: Che-Ming
authors: CM
authors: Yeh
authors: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan.
authors: Ting-Hsuan
authors: TH
authors: Yu
authors: Department of Pharmacology, College of Medicine, National Cheng Kung University, No. 1, University Rd, Tainan, 701, Taiwan.
authors: Kan-Hsun
authors: KH
authors: Chang
authors: Department of Pharmacology, College of Medicine, National Cheng Kung University, No. 1, University Rd, Tainan, 701, Taiwan.
authors: Chiung-Chun
authors: CC
authors: Huang
authors: Department of Pharmacology, College of Medicine, National Cheng Kung University, No. 1, University Rd, Tainan, 701, Taiwan. richard@mail.ncku.edu.tw.|Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan. richard@mail.ncku.edu.tw.
authors: Kuei-Sen
authors: KS
authors: Hsu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001369:Axons / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000473:pathology / Q000648:ultrastructure; D002443:Ceftriaxone / Q000494:pharmacology / Q000627:therapeutic use; D019070:Cell Lineage / Q000187:drug effects; D003907:Dexamethasone / Q000009:adverse effects*; D018450:Disease Progression; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009186:Myelin Sheath / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017207:Rats, Sprague-Dawley; D066127:White Matter / Q000293:injuries* / Q000473:pathology* / Q000503:physiopathology
chemical_list: D005904:Glial Fibrillary Acidic Protein; D002443:Ceftriaxone; D003907:Dexamethasone
keywords: Ceftriaxone; Dexamethasone; Hypoxia/ischemia; Oligodendrocyte; White matter injury