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Published Online
on August 6, 2009

Stroke. 2009
Published online before print August 6, 2009, doi: 10.1161/STROKEAHA.109.553248
A more recent version of this article appeared on October 1, 2009
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Submitted on March 19, 2009
Revised on May 28, 2009
Accepted on June 26, 2009

Intense Correlation Between Brain Infarction and Protein-Conjugated Acrolein

Ryotaro Saiki MS; Kazuhiro Nishimura PhD; Itsuko Ishii PhD; Tomohiro Omura PhD; Shigeru Okuyama PhD; Keiko Kashiwagi PhD; and Kazuei Igarashi PhD*

From the Graduate School of Pharmaceutical Sciences (R.S., K.N., I.I., K.I.), Chiba University, Chiba, Japan; Medicinal Research Laboratories, Taisho Pharmaceutical Co Ltd (T.O., S.O.), Saitama, Japan; Faculty of Pharmacy (K.K.), Chiba Institute of Science, Chiba, Japan; and Amine Pharma Research Institute (K.I.), Innovation Plaza at Chiba University, Chiba, Japan.

* To whom correspondence should be addressed. E-mail: iga16077{at}p.chiba-u.ac.jp.

Background and Purpose—We recently found that increases in plasma levels of protein-conjugated acrolein and polyamine oxidases, enzymes that produce acrolein, are good markers for stroke. The aim of this study was to determine whether the level of protein-conjugated acrolein is increased and levels of spermine and spermidine, the substrates of acrolein production, are decreased at the locus of infarction.

Methods—A unilateral infarction was induced in mouse brain by photoinduction after injection of Rose Bengal. The volume of the infarction was analyzed using the public domain National Institutes of Health image program. The level of protein-conjugated acrolein at the locus of infarction and in plasma was measured by Western blotting and enzyme-linked immunosorbent assay, respectively. The levels of polyamines at the locus of infarction and in plasma were measured by high-performance liquid chromatography.

Results—The level of protein-conjugated acrolein was greatly increased, and levels of spermine and spermidine were decreased at the locus of infarction at 24 hours after the induction of stroke. The size of infarction was significantly decreased by N-acetylcysteine, a scavenger of acrolein. It was also found that the increases in the protein-conjugated acrolein, polyamines, and polyamine oxidases in plasma were observed after the induction of stroke.

Conclusions—The results indicate that the induction of infarction is well correlated with the increase in protein-conjugated acrolein at the locus of infarction and in plasma.


Key words: acrolein • brain infarction • neuroprotective agents • polyamines • risk factors