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Int. J. Mol. Sci. 2017, 18(1), 187;

Neuroprotection by Caffeine in Hyperoxia-Induced Neonatal Brain Injury

Department of Neonatology, Charité, Universitätsmedizin Berlin, 13353 Berlin, Germany
Department of Physiology, Charité, Universitätsmedizin Berlin, 10117 Berlin, Germany
Department of Biochemistry and Biology, University of Potsdam, 14476 Potsdam, Germany
Department of Anesthesiology and Intensive Care Medicine, Charité, Universitätsmedizin Berlin, 13353 Berlin, Germany
Author to whom correspondence should be addressed.
Academic Editors: Melpo Christofidou-Solomidou and Thomas J. Goodwin
Received: 14 November 2016 / Revised: 4 January 2017 / Accepted: 12 January 2017 / Published: 18 January 2017
(This article belongs to the Special Issue Oxidative Stress and Space Biology: An Organ-Based Approach)
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Sequelae of prematurity triggered by oxidative stress and free radical-mediated tissue damage have coined the term “oxygen radical disease of prematurity”. Caffeine, a potent free radical scavenger and adenosine receptor antagonist, reduces rates of brain damage in preterm infants. In the present study, we investigated the effects of caffeine on oxidative stress markers, anti-oxidative response, inflammation, redox-sensitive transcription factors, apoptosis, and extracellular matrix following the induction of hyperoxia in neonatal rats. The brain of a rat pups at postnatal Day 6 (P6) corresponds to that of a human fetal brain at 28–32 weeks gestation and the neonatal rat is an ideal model in which to investigate effects of oxidative stress and neuroprotection of caffeine on the developing brain. Six-day-old Wistar rats were pre-treated with caffeine and exposed to 80% oxygen for 24 and 48 h. Caffeine reduced oxidative stress marker (heme oxygenase-1, lipid peroxidation, hydrogen peroxide, and glutamate-cysteine ligase catalytic subunit (GCLC)), promoted anti-oxidative response (superoxide dismutase, peroxiredoxin 1, and sulfiredoxin 1), down-regulated pro-inflammatory cytokines, modulated redox-sensitive transcription factor expression (Nrf2/Keap1, and NFκB), reduced pro-apoptotic effectors (poly (ADP-ribose) polymerase-1 (PARP-1), apoptosis inducing factor (AIF), and caspase-3), and diminished extracellular matrix degeneration (matrix metalloproteinases (MMP) 2, and inhibitor of metalloproteinase (TIMP) 1/2). Our study affirms that caffeine is a pleiotropic neuroprotective drug in the developing brain due to its anti-oxidant, anti-inflammatory, and anti-apoptotic properties. View Full-Text
Keywords: anti-oxidative response; caffeine; hyperoxia; oxidative stress; preterm infants; developing brain anti-oxidative response; caffeine; hyperoxia; oxidative stress; preterm infants; developing brain

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Endesfelder, S.; Weichelt, U.; Strauß, E.; Schlör, A.; Sifringer, M.; Scheuer, T.; Bührer, C.; Schmitz, T. Neuroprotection by Caffeine in Hyperoxia-Induced Neonatal Brain Injury. Int. J. Mol. Sci. 2017, 18, 187.

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