(Stroke. 2001;32:1652.)
© 2001 American Heart Association, Inc.
Original Contributions |
Transgenic CuZn-Superoxide Dismutase Inhibits NO Synthase Induction in Experimental Subarachnoid Hemorrhage
From the Departments of Neurosurgery (A.S., T.K., T.Y.) and Biochemistry (I.K., S.T., H.O.), Tohoku University Graduate School of Medicine, Sendai, Japan; the Department of Neurosurgery (H.K.), Yamagata University School of Medicine, Yamagata, Japan; and the Department of Neurosurgery and Neurology (P.H.C.), Stanford University, Palo Alto, Calif.
Correspondence to Atsushi Saito, MD, Department of Neurosurgery, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aoba-ku, Sendai 980-8574, Japan. E-mail atsushi{at}nsg.med.tohoku.ac.jp
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 inhibitory 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-
B, a major
transcription factor of iNOS gene, was also immunohistochemically
examined.
Results—In
nontransgenic mice, SAH-induced iNOS protein 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-induced 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-B was
immunohistochemically detected in the cerebral cortices of
nontransgenic mice but not in those of SOD-transgenic
mice.
Conclusions—These results indicate 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.
Editorial Comment
Section of Neurosurgery, University of Chicago Medical Center, Chicago, Illinois
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