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      Maternal PUFA ω-3 Supplementation Prevents Neonatal Lung Injuries Induced by Hyperoxia in Newborn Rats

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          Abstract

          Bronchopulmonary dysplasia (BPD) is one of the most common complications of prematurity, occurring in 30% of very low birth weight infants. The benefits of dietary intake of polyunsaturated fatty acids ω-3 (PUFA ω-3) during pregnancy or the perinatal period have been reported. The aim of this study was to assess the effects of maternal PUFA ω-3 supplementation on lung injuries in newborn rats exposed to prolonged hyperoxia. Pregnant female Wistar rats ( n = 14) were fed a control diet ( n = 2), a PUFA ω-6 diet ( n = 6), or a PUFA ω-3 diet ( n = 6), starting with the 14th gestation day. At Day 1, female and newborn rats (10 per female) were exposed to hyperoxia (O 2, n = 70) or to the ambient air (Air, n = 70). Six groups of newborns rats were obtained: PUFA ω-6/O 2 ( n = 30), PUFA ω-6/air ( n = 30), PUFA ω-3/O 2 ( n = 30), PUFA ω-3/air ( n = 30), control/O 2 ( n = 10), and control/air ( n = 10). After 10 days, lungs were removed for analysis of alveolarization and pulmonary vascular development. Survival rate was 100%. Hyperoxia reduced alveolarization and increased pulmonary vascular wall thickness in both control ( n = 20) and PUFA ω-6 groups ( n = 60). Maternal PUFA ω-3 supplementation prevented the decrease in alveolarization caused by hyperoxia ( n = 30) compared to PUFA ω-6/O 2 ( n = 30) or to the control/O 2 ( n = 10), but did not significantly increase the thickness of the lung vascular wall. Therefore, maternal PUFA ω-3 supplementation may protect newborn rats from lung injuries induced by hyperoxia. In clinical settings, maternal PUFA ω-3 supplementation during pregnancy and during lactation may prevent BPD development after premature birth.

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          Animal models of bronchopulmonary dysplasia. The term mouse models.

          The etiology of bronchopulmonary dysplasia (BPD) is multifactorial, with genetics, ante- and postnatal sepsis, invasive mechanical ventilation, and exposure to hyperoxia being well described as contributing factors. Much of what is known about the pathogenesis of BPD is derived from animal models being exposed to the environmental factors noted above. This review will briefly cover the various mouse models of BPD, focusing mainly on the hyperoxia-induced lung injury models. We will also include hypoxia, hypoxia/hyperoxia, inflammation-induced, and transgenic models in room air. Attention to the stage of lung development at the timing of the initiation of the environmental insult and the duration of lung injury is critical to attempt to mimic the human disease pulmonary phenotype, both in the short term and in outcomes extending into childhood, adolescence, and adulthood. The various indexes of alveolar and vascular development as well as pulmonary function including pulmonary hypertension will be highlighted. The advantages (and limitations) of using such approaches will be discussed in the context of understanding the pathogenesis of and targeting therapeutic interventions to ameliorate human BPD.
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            Inflammation and bronchopulmonary dysplasia: a continuing story.

            Increasing evidence indicates that bronchopulmonary dysplasia (BPD) results, at least in part, from an imbalance between pro-inflammatory and anti-inflammatory mechanisms, with a persistent imbalance that favours pro-inflammatory mechanisms. The inflammatory response is characterised by an accumulation of neutrophils and macrophages in the airways and pulmonary tissue of preterm infants and, moreover, by an arsenal of pro-inflammatory mediators which affect the alveolar capillary unit and tissue integrity. As well as pro-inflammatory cytokines and toxic oxygen radicals, various lipid mediators as well as potent proteases may be responsible for acute lung injury. During the last decade it has become evident that multiple pre- and postnatal events contribute to the development of BPD in preterm infants. Chorioamnionitis and cytokine exposure in utero, plus sequential lung injury caused by postnatal resuscitation, oxygen toxicity, volu-, barotrauma and infection all lead to a pulmonary inflammatory response which is most probably associated with aberrant wound healing and an inhibition of alveolarisation as well as vascular development in the immature lungs of very preterm infants, causing the 'new BPD'.
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              Chronic lung disease in the preterm infant. Lessons learned from animal models.

              Neonatal chronic lung disease, also known as bronchopulmonary dysplasia (BPD), is the most common complication of premature birth, affecting up to 30% of very low birth weight infants. Improved medical care has allowed for the survival of the most premature infants and has significantly changed the pathology of BPD from a disease marked by severe lung injury to the "new" form characterized by alveolar hypoplasia and impaired vascular development. However, increased patient survival has led to a paucity of pathologic specimens available from infants with BPD. This, combined with the lack of a system to model alveolarization in vitro, has resulted in a great need for animal models that mimic key features of the disease. To this end, a number of animal models have been created by exposing the immature lung to injuries induced by hyperoxia, mechanical stretch, and inflammation and most recently by the genetic modification of mice. These animal studies have 1) allowed insight into the mechanisms that determine alveolar growth, 2) delineated factors central to the pathogenesis of neonatal chronic lung disease, and 3) informed the development of new therapies. In this review, we summarize the key findings and limitations of the most common animal models of BPD and discuss how knowledge obtained from these studies has informed clinical care. Future studies should aim to provide a more complete understanding of the pathways that preserve and repair alveolar growth during injury, which might be translated into novel strategies to treat lung diseases in infants and adults.
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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                14 September 2015
                September 2015
                : 16
                : 9
                : 22081-22093
                Affiliations
                [1 ]EA 4489 Environnement Périnatal et Santé, Pôle Recherche Faculté de Médecine, Université Lille Nord de France, Lille 59045, France; E-Mails: dyuti.sharma@ 123456chru-lille.fr (D.S.); armande.subayi@ 123456chru-lille.fr (A.S.N.); estelle.aubry@ 123456chru-lille.fr (E.A.); ali.houeijeh@ 123456chru-lille.fr (A.H.); laura.butruille@ 123456hotmail.fr (L.B.); veronique.debarge@ 123456chru-lille.fr (V.H.-D.); remi.besson@ 123456chru-lille.fr (R.B.); philippe.deruelle@ 123456chru-lille.fr (P.D.)
                [2 ]Clinique de Chirurgie et Orthopédie de l’Enfant, Pôle Enfant, Hôpital Jeanne de Flandre, CHRU Lille, Lille 59037, France
                [3 ]Clinique de Néonatologie, Pôle Femme, Mère et Nouveau-Né, Hôpital Jeanne de Flandre, CHRU Lille, Lille 59037, France
                [4 ]Clinique de Gynécologie-Obstétrique, Pôle Femme, Mère et Nouveau-Né, Hôpital Jeanne de Flandre, CHRU Lille, Lille 59037, France
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: laurent.storme@ 123456chru-lille.fr ; Tel.: +33-320-446-213; Fax: +33-320-446-236.
                Article
                ijms-16-22081
                10.3390/ijms160922081
                4613298
                26389878
                0aa95f1b-0e64-4a78-86e7-2b21d7857abf
                © 2015 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 30 June 2015
                : 07 September 2015
                Categories
                Article

                Molecular biology
                pufa ω-3,bronchopulmonary dysplasia,prematurity,diet
                Molecular biology
                pufa ω-3, bronchopulmonary dysplasia, prematurity, diet

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