Inducible nitric oxide synthase does not mediate brain damage after transient focal cerebral ischemia in mice

Harald Prüss, Konstantin Prass, Leyli Ghaeni, Milan Milosevic, Claudia Muselmann, Dorette Freyer, Georg Royl, Uwe Reuter, Nevena Baeva, Ulrich Dirnagl, Andreas Meisel, Josef Priller

Research output: Contribution to journalArticlepeer-review

Abstract

Nitric oxide produced by the inducible nitric oxide synthase (iNOS) is believed to participate in the pathogenic events after cerebral ischemia. In this study, we examined the expression of iNOS in the brain after transient focal cerebral ischemia in mice. We detected differential expression of exons 2 and 3 of iNOS mRNA (16-fold upregulation at 24 to 72 h after middle cerebral artery occlusion, MCAO) compared with exons 6 to 8, 12 to 14, 21 to 22, and 26 to 27 (2- to 5-fold upregulation after 72 and 96 h), which would be compatible with alternative splicing. Expression levels of iNOS mRNA were too low for detection by the Northern blot analysis. Using specific antibodies, we did not detect any iNOS immunoreactivity in the mouse brain 1 to 5 days after MCAO, although we detected iNOS immunoreactivity in the lungs of mice with stroke-associated pneumonia, and in mouse and rat dura mater after lipopolysaccharide administration. In chimeric iNOS-deficient mice transplanted with wild-type bone marrow (BM) cells expressing the green fluorescent protein (GFP) or in wild-type mice transplanted with GFP(+) iNOS-deficient BM cells, no expression of iNOS was detected in GFP(+) leukocytes invading the ischemic brain or in resident brain cells. Moreover, both experimental groups did not show any differences in infarct size. Analysis of three different strains of iNOS-deficient mice and wild-type controls confirmed that infarct size was independent of iNOS deletion, but strongly confounded by the genetic background of mouse strains. In conclusion, our data suggest that iNOS is not a universal mediator of brain damage after cerebral ischemia.

Original languageEnglish
Pages (from-to)526-39
Number of pages14
JournalJournal of Cerebral Blood Flow and Metabolism
Volume28
Issue number3
DOIs
Publication statusPublished - Mar 2008

Keywords

  • Alternative Splicing
  • Animals
  • Brain Chemistry
  • Brain Ischemia
  • Exons
  • Ischemic Attack, Transient
  • Lung
  • Mice
  • Mice, Knockout
  • Nitric Oxide Synthase Type II
  • RNA, Messenger
  • Up-Regulation
  • Journal Article
  • Research Support, Non-U.S. Gov't

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