title: Statins prevent adverse effects of postnatal glucocorticoid therapy on the developing brain in rats.
abstract: BACKGROUND
  Postnatal glucocorticoid therapy in the treatment of chronic lung disease benefits lung function, however it adversely affects brain development. We hypothesized that combined postnatal glucocorticoid and statin therapy diminishes adverse effects of glucocorticoids on the developing brain.
  
  
  METHODS
  On postnatal days (P) 1-3, one male pup per litter received i.p. injections of saline control (C), n = 13) or dexamethasone (0.5, 0.3, 0.1 µg/g; D, n = 13), ± pravastatin (10 mg/kg i.p.; CP, n = 12; DP, n = 15). Statins or saline continued from P4-6. At P21, brains were perfusion fixed for histological and stereological analyses.
  
  
  RESULTS
  Relative to controls, dexamethasone reduced total (837 ± 23 vs. 723 ± 37), cortical (378 ± 12 vs. 329 ± 15), and deep gray matter (329 ± 12 vs. 284 ± 15) volume (mm(3)), cortical neuronal number (23 ± 1 vs. 19 ± 1 × 10(6)), and hippocampal neuronal soma volume (CA1: 1,206 ± 32 vs. 999 ± 32; dentate gyrus: 679 ± 28 vs. 542 ± 24 µm(3); all P < 0.05). Dexamethasone increased the glial fibrillary acidic protein-positive astrocyte density in the white matter (96 ± 2 vs. 110 ± 4/0.1 mm(2)); P < 0.05. These effects no longer occurred in brains from pups treated with combined dexamethasone and pravastatin. Pravastatin alone had no effect on these variables.
  
  
  CONCLUSIONS
  Concomitant dexamethasone with statins in premature infants may be safer for the developing brain than dexamethasone alone in the treatment of chronic lung disease.
authors.affiliation: Department of Perinatology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Deodata
authors.initials: D
authors.lastname: Tijsseling
authors.affiliation: Department of Physiology, Development & Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Camm
authors.affiliation: Department of Physiology, Development & Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: Hans G
authors.initials: HG
authors.lastname: Richter
authors.affiliation: Department of Physiology, Development & Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: Emilio A
authors.initials: EA
authors.lastname: Herrera
authors.affiliation: Department of Physiology, Development & Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Kane
authors.affiliation: Department of Physiology, Development & Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: Youguo
authors.initials: Y
authors.lastname: Niu
authors.affiliation: Department of Physiology, Development & Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Cross
authors.affiliation: Department of Perinatology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Willem B
authors.initials: WB
authors.lastname: de Vries
authors.affiliation: Department of Perinatology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Jan B
authors.initials: JB
authors.lastname: Derks
authors.affiliation: Department of Physiology, Development & Neuroscience, University of Cambridge, Cambridge, UK.
authors.forename: Dino A
authors.initials: DA
authors.lastname: Giussani
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000254:growth & development; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
chemical_list: D005938:Glucocorticoids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009569:Nitric Oxide