Dual action of NO synthases on blood flow and infarct volume consecutive to neonatal focal cerebral ischemia

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

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Research into neonatal ischemic brain damage is impeded by the lack of a complete understanding of the initial hemodynamic mechanisms resulting in a lesion, particularly that of NO-mediated vascular mechanisms. In a neonatal stroke rat model, we recently show that collateral recruitment contributes to infarct size variability. Non-specific and selective NO synthase (NOS) inhibition was evaluated on cerebral blood-flow changes and outcome in a P7 rat model of arterial occlusion (left middle cerebral artery electrocoagulation with 50 min occlusion of both common carotid arteries). Blood-flow changes were measured by using ultrasound imaging with sequential Doppler recordings in both internal carotid arteries and basilar trunk. Cortical perfusion was measured by using laser Doppler flowmetry. We showed that global NOS inhibition significantly reduced collateral support and cortical perfusion (collateral failure), and worsened the ischemic injury in both gender. Conversely, endothelial NOS inhibition increased blood-flows and aggravated volume lesion in males, whereas in females blood-flows did not change and infarct lesion was significantly reduced. These changes were associated with decreased phosphorylation of neuronal NOS at Ser(847) in males and increased phosphorylation in females at 24h, respectively. Neuronal NOS inhibition also increased blood-flows in males but not in females, and did not significantly change infarct volumes compared to their respective PBS-treated controls. In conclusion, both nNOS and eNOS appear to play a key role in modulating arterial blood flow during ischemia mainly in male pups with subsequent modifications in infarct lesion.

Original languageEnglish (US)
Pages (from-to)50-7
Number of pages8
JournalExperimental Neurology
Volume236
Issue number1
DOIs
StatePublished - Jul 2012

Keywords

  • Animals
  • Animals, Newborn
  • Brain Infarction
  • Cerebrovascular Circulation
  • Disease Models, Animal
  • Female
  • Humans
  • Hypoxia-Ischemia, Brain
  • Infant, Newborn
  • Leukomalacia, Periventricular
  • Male
  • Nitric Oxide Synthase Type I
  • Nitric Oxide Synthase Type III
  • Rats
  • Rats, Wistar
  • Journal Article
  • Research Support, Non-U.S. Gov't

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