Statins Prevent Adverse Effects of Postnatal Glucocorticoid Therapy on the Developing Brain in Rats

Tijsseling, Deodata; Camm, Emily J.; Richter, Hans G.; Herrera, Emilio A.; Kane, Andrew D.; Niu, Youguo; Cross, Christine M.; de Vries, Willem B.; Derks, Jan B.; Giussani, Dino A.


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.

Más información

Título de la Revista: PEDIATRIC RESEARCH
Volumen: 74
Fecha de publicación: 2013
Página de inicio: 639
Página final: 645
Idioma: Inglés
Financiamiento/Sponsor: Supported by the British Heart Foundation, the Biotechnology and Biological Sciences Research Council, and the Fonds Internationalisering, University Medical Center, Utrecht, The Netherlands.

doi: 10.1038/pr.2013.152

Notas: WOS Core Collection ISI