title: Inhaled nitric oxide reduces brain damage by collateral recruitment in a neonatal stroke model.
abstract: OBJECTIVE
  We recently demonstrated that endogenous nitric oxide (NO) modulates collateral blood flow in a neonatal stroke model in rats. The inhalation of NO (iNO) has been found to be neuroprotective after ischemic brain damage in adults. Our objective was to examine whether iNO could modify cerebral blood flow during ischemia-reperfusion and reduce lesions in the developing brain.
  
  
  METHODS
  In vivo variations in cortical NO concentrations occurring after 20-ppm iNO exposure were analyzed using the voltammetric method in P7 rat pups. Inhaled NO-mediated blood flow velocities were measured by ultrasound imaging with sequential Doppler recordings in both internal carotid arteries and the basilar trunk under basal conditions and in a neonatal model of ischemia-reperfusion. The hemodynamic effects of iNO (5 to 80 ppm) were correlated with brain injury 48 hours after reperfusion.
  
  
  RESULTS
  Inhaled NO (20 ppm) significantly increased NO concentrations in the P7 rat cortex and compensated for the blockade of endogenous NO synthesis under normal conditions. Inhaled NO (20 ppm) during ischemia increased blood flow velocities and significantly reduced lesion volumes by 43% and cellular damage. In contrast, both 80 ppm iNO given during ischemia and 5 or 20 ppm iNO given 30 minutes after reperfusion were detrimental.
  
  
  CONCLUSIONS
  Our findings strongly indicate that, with the appropriate timing, 20 ppm iNO can be transported into the P7 rat brain and mediated blood flow redistribution during ischemia leading to reduced infarct volume and cell injury.
authors.affiliation: University Paris Diderot, Sorbonne Paris Cité, INSERM U676 and NICU, Robert Debré Children's Hospital, 48 Bd Sérurier 75019 Paris, France.
authors.forename: Christiane
authors.initials: C
authors.lastname: Charriaut-Marlangue
authors.forename: Philippe
authors.initials: P
authors.lastname: Bonnin
authors.forename: Abdallah
authors.initials: A
authors.lastname: Gharib
authors.forename: Pierre-Louis
authors.initials: PL
authors.lastname: Leger
authors.forename: Sonia
authors.initials: S
authors.lastname: Villapol
authors.forename: Marc
authors.initials: M
authors.lastname: Pocard
authors.forename: Pierre
authors.initials: P
authors.lastname: Gressens
authors.forename: Sylvain
authors.initials: S
authors.lastname: Renolleau
authors.forename: Olivier
authors.initials: O
authors.lastname: Baud
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000831:Animals, Newborn; D001930:Brain Injuries / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003097:Collateral Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D009569:Nitric Oxide / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000473:pathology*
chemical_list: D018696:Neuroprotective Agents; D009569:Nitric Oxide