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Protective effect of 20‐HETE inhibition on infarct volume following temporary middle cerebral artery occlusion is not associated with changes in cerebral blood flow
Author(s) -
Renic Marija,
Flasch Averia K,
Klaus Judy A,
Miyata Noriyuki,
Koehler Raymond C,
Harder David R,
Roman Richard J
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1383-a
Subject(s) - cerebral blood flow , anesthesia , medicine , middle cerebral artery , occlusion , neuroprotection , ischemia , infarction , cardiology , myocardial infarction
The purpose of this study was to examine the effects of a new 20‐HETE synthesis inhibitor, TS‐011, on infarct volume, regional cerebral blood flow (rCBF), and the concentration of 20‐HETE in the brain following transient occlusion of the middle cerebral artery (t‐MCAO) in Wistar rats. Administration of TS‐011 (0.1mg/kg i.v.) 30 min prior to reperfusion reduced infarct volume in the cortex by 70% and total infarct volume by 55 % (n=8). There were no differences in rCBF at any time during the experiment in TS‐011 and vehicle‐treated groups. In other experiments rCBF was simultaneously monitored at 4 points over the ischemic hemisphere. Again, TS‐011 had no effect on rCBF. Pretreatment of rats with TS‐011 (0.1 mg/kg i.v.) 30 min prior to t‐MCAO reduced the infarct volume by 60% (n=7) and increased rCBF by about 30–40% following reperfusion, but it had no greater protective effect on infarct volume than giving TS‐011 prior to reperfusion. 20‐HETE levels in the brain 30 min following reperfusion was reduced by about 80% in TS‐011‐pretreated animals (n=6). These results indicate that TS‐011 reduces infarct volume in rats with t‐MCAO when given before or during occlusion. The protective effect of TS‐011 is not associated with changes in rCBF and may be due to a neuroprotective effect. This study was supported in part by National Institute of Health Grants HL‐59996.