Inhaled nitric oxide reduces brain damage by collateral recruitment in a neonatal stroke model

Christiane Charriaut-Marlangue, Philippe Bonnin, Abdallah Gharib, Pierre-Louis Leger, Sonia Villapol, Marc Pocard, Pierre Gressens, Sylvain Renolleau, Olivier Baud

Research output: Contribution to journalArticlepeer-review

68 Scopus citations


BACKGROUND AND PURPOSE: 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.

Original languageEnglish (US)
Pages (from-to)3078-84
Number of pages7
JournalStroke; a journal of cerebral circulation
Issue number11
StatePublished - Nov 2012


  • Administration, Inhalation
  • Animals
  • Animals, Newborn
  • Brain Injuries
  • Cerebrovascular Circulation
  • Collateral Circulation
  • Disease Models, Animal
  • Hemodynamics
  • Neuroprotective Agents
  • Nitric Oxide
  • Rats
  • Rats, Wistar
  • Stroke
  • Journal Article


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