Statins prevent adverse effects of postnatal glucocorticoid therapy on the developing brain in rats
| Autor: | Willem B. de Vries, Deodata Tijsseling, Andrew D. Kane, Christine M. Cross, Dino A. Giussani, Emily J. Camm, Emilio A. Herrera, Jan B. Derks, Hans Richter, Youguo Niu |
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| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Nitric Oxide Bioinformatics Pregnancy Internal medicine medicine Animals cardiovascular diseases Rats Wistar Adverse effect Glucocorticoids business.industry Body Weight Brain nutritional and metabolic diseases Organ Size Rats Endocrinology Glucocorticoid therapy Pediatrics Perinatology and Child Health Female lipids (amino acids peptides and proteins) Hydroxymethylglutaryl-CoA Reductase Inhibitors business hormones hormone substitutes and hormone antagonists |
| Zdroj: | Pediatric Research. 74:639-645 |
| ISSN: | 1530-0447 0031-3998 |
| DOI: | 10.1038/pr.2013.152 |
| Popis: | 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.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.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 P0.05). Dexamethasone increased the glial fibrillary acidic protein-positive astrocyte density in the white matter (96 ± 2 vs. 110 ± 4/0.1 mm(2)); P0.05. These effects no longer occurred in brains from pups treated with combined dexamethasone and pravastatin. Pravastatin alone had no effect on these variables.Concomitant dexamethasone with statins in premature infants may be safer for the developing brain than dexamethasone alone in the treatment of chronic lung disease. |
| Databáze: | OpenAIRE |
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