Abstract:
BACKGROUND AND PURPOSE:Arachidonic acid that is released following cerebral ischemia can be metabolized to 20-hydroxyeicosatetraenoic acid (20-HETE). 20-HETE is a potent vasoconstrictor that may contribute to ischemic injury. This study examined the effects of blockading the synthesis of 20-HETE with TS-011 on infarct size after transient occlusion of the middle cerebral artery (MCAO) of rats and after thromboembolic stroke in monkeys. METHODS:Rats were treated with TS-011 or vehicle at various times after MCAO. Infarct size was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining and plasma levels of 20-HETE were determined by liquid chromatography mass spectrometry (LC/MS). The effect of TS-011 on infarct size was also studied in monkeys after introduction of a clot into the internal carotid artery. RESULTS:Plasma levels of 20-HETE increased after MCAO in rats. TS-011 (0.01 to 1.0 mg/kg per hour) reduced infarct volume by 40%. Chronic administration of TS-011 for 7 days reduced neurological deficits after MCAO in rats. TS-011 given in combination with tissue plasminogen activator also improved neurological outcome in the stroke model in monkeys. CONCLUSIONS:These results suggest that blockade of the formation of 20-HETE with TS-011 may be useful for the treatment of ischemic stroke.
journal_name
Strokejournal_title
Strokeauthors
Omura T,Tanaka Y,Miyata N,Koizumi C,Sakurai T,Fukasawa M,Hachiuma K,Minagawa T,Susumu T,Yoshida S,Nakaike S,Okuyama S,Harder DR,Roman RJdoi
10.1161/01.STR.0000217398.37075.07subject
Has Abstractpub_date
2006-05-01 00:00:00pages
1307-13issue
5eissn
0039-2499issn
1524-4628pii
01.STR.0000217398.37075.07journal_volume
37pub_type
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