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Published on: November 20, 2015
Statins prevent adverse effects of postnatal glucocorticoid therapy on the developing brain in rats
Deodata Tijsseling1, Emily J Camm2, Hans G Richter2
1Department of Perinatology, University Medical Center Utrecht, Utrecht, The Netherlands.
Insights
Combining dexamethasone with pravastatin may protect the developing brain from adverse effects seen with dexamethasone alone. This combination therapy could offer a safer approach for treating chronic lung disease in premature infants.
Area of Science:
- Neuroscience
- Pharmacology
- Neonatal Medicine
Background:
- Postnatal glucocorticoid therapy is used for chronic lung disease but can harm brain development.
- The study investigates if statin therapy can mitigate these adverse neurological effects.
Purpose of the Study:
- To determine if combined dexamethasone and pravastatin therapy reduces the negative impact of dexamethasone on brain development.
- To evaluate the neuroprotective potential of statins when co-administered with glucocorticoids.
Main Methods:
- Animal model using rat pups treated with dexamethasone, pravastatin, or both from postnatal days 1-6.
- Histological and stereological analyses were performed on brain tissue at postnatal day 21.
- Dose-dependent effects of dexamethasone were assessed, with and without pravastatin co-administration.
Main Results:
- Dexamethasone significantly reduced brain volume, neuronal number, and neuronal soma size.
- Dexamethasone increased astrocyte density in white matter, indicating inflammation.
- Combined dexamethasone and pravastatin treatment prevented these adverse effects, while pravastatin alone had no impact.
Conclusions:
- Concomitant use of statins with dexamethasone may be a safer strategy for treating chronic lung disease in premature infants.
- This combination therapy shows promise in protecting the developing brain from glucocorticoid-induced damage.
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.
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