title: Impact of inhaled nitric oxide on white matter damage in growth-restricted neonatal rats.
abstract: BACKGROUND
  Fetal growth restriction is the second leading cause of perinatal morbidity and mortality, and neonates with intrauterine growth retardation (IUGR) have increased neurocognitive and neuropsychiatric morbidity. These neurocognitive impairments are mainly related to injury of the developing brain associated with IUGR. Growing evidence from preclinical models of brain injury in both adult and neonatal rodents supports the view that nitric oxide can promote neuroprotection.
  
  
  METHODS
  In a model of IUGR induced by protracted gestational hypoxia leading to diffuse white matter injury, we subjected neonatal rats to low dose (5 ppm) but long-lasting (7 d) exposure to inhaled NO (iNO). We used a combination of techniques, including immunohistochemistry, quantitative PCR, and cognitive assessment, to assess neuroprotection.
  
  
  RESULTS
  Antenatal hypoxia-induced IUGR was associated with severe neuroinflammation and delayed myelination. iNO exposure during the first postnatal week significantly attenuated cell death and microglial activation, enhanced oligodendroglial proliferation and finally improved myelination. Remarkably, iNO was associated with the specific upregulation of P27kip1, which initiates oligodendrocytic differentiation. Finally, iNO counteracted the deleterious effects of hypoxia on learning abilities.
  
  
  CONCLUSIONS
  This study provides new evidence that iNO could be effective in preventing brain damage and/or enhancing repair of the developing brain.
authors.affiliation: 1] INSERM UMR1141, Université Paris Diderot, Paris, France [2] PremUP Foundation, Paris, France.
authors.forename: Hoa
authors.initials: H
authors.lastname: Pham
authors.affiliation: 1] INSERM UMR1141, Université Paris Diderot, Paris, France [2] PremUP Foundation, Paris, France.
authors.forename: An Phan
authors.initials: AP
authors.lastname: Duy
authors.affiliation: 1] INSERM UMR1141, Université Paris Diderot, Paris, France [2] PremUP Foundation, Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Pansiot
authors.affiliation: 1] INSERM UMR1141, Université Paris Diderot, Paris, France [2] PremUP Foundation, Paris, France.
authors.forename: Bieke
authors.initials: B
authors.lastname: Bollen
authors.affiliation: 1] INSERM UMR1141, Université Paris Diderot, Paris, France [2] PremUP Foundation, Paris, France.
authors.forename: Jorge
authors.initials: J
authors.lastname: Gallego
authors.affiliation: 1] INSERM UMR1141, Université Paris Diderot, Paris, France [2] PremUP Foundation, Paris, France.
authors.forename: Christiane
authors.initials: C
authors.lastname: Charriaut-Marlangue
authors.affiliation: 1] INSERM UMR1141, Université Paris Diderot, Paris, France [2] PremUP Foundation, Paris, France [3] Neonatal Intensive Care Unit, Robert Debré Children's Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Baud
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000473:pathology; D001522:Behavior, Animal; D001930:Brain Injuries / Q000473:pathology / Q000517:prevention & control; D003072:Cognition Disorders / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D005317:Fetal Growth Retardation; D000860:Hypoxia; D007150:Immunohistochemistry; D007858:Learning; D009186:Myelin Sheath / Q000737:chemistry; D018696:Neuroprotective Agents / Q000737:chemistry*; D009569:Nitric Oxide / Q000008:administration & dosage*; D009836:Oligodendroglia / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D066127:White Matter / Q000187:drug effects* / Q000473:pathology
chemical_list: D018696:Neuroprotective Agents; D009569:Nitric Oxide