• Hoa Pham, Gaelle Vottier, Julien Pansiot, Sy Duong-Quy, Bieke Bollen, Jérémie Dalous, Jorge Gallego, Jean-Christophe Mercier, Anh Tuan Dinh-Xuan, Philippe Bonnin, Christiane Charriaut-Marlangue, and Olivier Baud.
• INSERM, UMR 676, 75019 Paris, France; Université Paris Diderot, UFR de médecine Denis Diderot, Sorbonne Paris Cité, 75010 Paris, France; PremUP foundation, 75014 Paris, France.
• Exp. Neurol. 2014 Feb 1;252:114-23.

AbstractWhite matter damage (WMD) and bronchopulmonary dysplasia (BPD) are the two main complications occurring in very preterm infants. Inhaled nitric oxide (iNO) has been proposed to promote alveolarization in the developing lung, and we have reported that iNO promotes myelination and induces neuroprotection in neonatal rats with excitotoxic brain damage. Our hypothesis is that, in addition to its pulmonary effects, iNO may be neuroprotective in rat pups exposed to hyperoxia. To test this hypothesis, we exposed rat pups to hyperoxia, and we assessed the impact of iNO on WMD and BPD. Rat pups were exposed to either hyperoxia (80% FiO2) or to normoxia for 8 days. Both groups received iNO (5 ppm) or air. We assessed the neurological and pulmonary effects of iNO in hyperoxia-injured rat pups using histological, molecular and behavioral approaches. iNO significantly attenuated the severity of hyperoxia-induced WMD induced in neonatal rats. Specifically, iNO decreased white matter inflammation, cell death, and enhanced the density of proliferating oligodendrocytes and oligodendroglial maturation. Furthermore, iNO triggered an early upregulation of P27kip1 and brain-derived growth factor (BDNF). Whereas hyperoxia disrupted early associative abilities, iNO treatment maintained learning scores to a level similar to that of control pups. In contrast to its marked neuroprotective effects, iNO induced only small and transient improvements of BPD. These findings suggest that iNO exposure at low doses is specifically neuroprotective in an animal model combining injuries of the developing lung and brain that mimicked BPD and WMD in preterm infants.Copyright © 2013 Elsevier Inc. All rights reserved.

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