Transgenic CuZn-superoxide dismutase inhibits NO synthase induction in experimental subarachnoid hemorrhage

Atsushi Saito, Hideyuki Kamii, Ichiro Kato, Shin Takasawa, Takeo Kondo, Pak H. Chan, Hiroshi Okamoto, Takashi Yoshimoto

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)

Abstract

Background and Purpose - The expression of inducible NO synthase (iNOS) after experimental subarachnoid hemorrhage (SAH) has been postulated to play a critical role in the pathogenesis of SAH and subsequent cerebral vasospasm. The inventory effect of CuZn-superoxide dismutase (CuZn-SOD) on the induction of iNOS after SAH was examined by using transgenic mice overexpressing CuZn-SOD. Methods - SOD-transgenic mice and nontransgenic littermates were subjected to SAH by endovascular perforation of the left anterior cerebral artery. The iNOS mRNA expression after SAH was determined by reverse transcription-polymerase chain reaction, and the distribution of iNOS-positive cells was immunohistochemically examined. The nuclear expression of activated nuclear factor-κB, a major transcription factor of iNOS gene, was also immunohistochemically examined. Results - In nontransgenic mice, SAH-induced iNOS protien and mRNA expressions in the arteries of basal cistern as well as in the cerebral cortex were demonstrated by immunohistochemistry and reverse transcription-polymerase chain reaction. SAH-inducedb iNOS protein and mRNA expressions in those tissues were much reduced in SOD-transgenic mice compared with nontransgenic mice. Moreover, the nuclear expression of the activated form of nuclear factor-κB was immunohistochemically detected in the cerebral cortices of nontransgenic mice but not in those of SOD-transgenic mice. Conclusion - These results indicated that oxygen-derived free radicals, particularly superoxide, play an important role in the iNOS gene expression after SAH and provide a molecular basis for the protective role of SOD against vasospasm after SAH.

Original languageEnglish
Pages (from-to)1652-1656
Number of pages5
JournalStroke
Volume32
Issue number7
DOIs
Publication statusPublished - 2001

Keywords

  • Cerebral ischemia, transient
  • Nitric oxide
  • Subarachnoid hemorrhage
  • Superoxide dismutase

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialised Nursing

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