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Pediatr Res. 2013 Dec;74(6):639-45. doi: 10.1038/pr.2013.152. Epub 2013 Sep 3.

Statins prevent adverse effects of postnatal glucocorticoid therapy on the developing brain in rats.

Author information

1
Department of Perinatology, University Medical Center Utrecht, Utrecht, The Netherlands.
2
Department of Physiology, Development & Neuroscience, University of Cambridge, Cambridge, UK.

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.

CONCLUSION:

Concomitant dexamethasone with statins in premature infants may be safer for the developing brain than dexamethasone alone in the treatment of chronic lung disease.

PMID:
24002330
DOI:
10.1038/pr.2013.152
[Indexed for MEDLINE]

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