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Atorvastatin enhances hypothermia-induced neuroprotection after stroke

Cited 20 time in Web of Science Cited 23 time in Scopus
Authors
Lee, Seung-Hoon; Kim, Yoon-Hee; Kim, Young-Ju; Yoon, Byung-Woo
Issue Date
2008-09-05
Publisher
Elsevier
Citation
J Neurol Sci. 2008;275(1-2):64-68
Keywords
AnimalsAntigens, CD11b/metabolismBrain Infarction/etiology/*prevention & controlDisease Models, AnimalHeptanoic Acids/*therapeutic useHydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic useHypothermia, Induced/*methodsMagnetic Resonance ImagingMaleNeurologic ExaminationNitric Oxide Synthase Type II/metabolismPyrroles/*therapeutic useRatsRats, Sprague-DawleyStatistics, NonparametricStroke/complications/*therapy
Abstract
BACKGROUND: Both statin and hypothermia protect the brain from focal cerebral ischemia. In this study, we sought to determine whether statin pretreatment enhances the efficacy of hypothermia and extends the therapeutic time window of hypothermia. METHODS: Rats were subjected to focal cerebral ischemia for 2 h. Initially, we tested the efficacy of atorvastatin pretreatment (1 mg/kg, daily for 10 days before ischemia) and hypothermia (32-33 degrees C for 2 h at onset of ischemia) in combination, and then we examined the effects of atorvastatin pretreatment on the therapeutic time window of hypothermia (3 or 6 h after ischemia). RESULTS: Both atorvastatin (27.5+/-4.6) and hypothermia (25.9+/-6.3%) reduced infarct volumes significantly as compared with the control group (40.5+/-3.3%; p<0.05 in each comparison). These two treatments in combination further decreased infarct volumes (13.2+/-6.3%), and remarkably reduced the staining extents of Ox-42, and of inducible nitric oxide synthase. In addition, hypothermia alone was found to be effective when applied at 3 h after ischemia, but not when applied at 6 h. However, atorvastatin pretreatment and hypothermia led to a significant reduction in infarct volumes even when hypothermia was applied at 6 h. CONCLUSIONS: It was found that atorvastatin pretreatment strongly enhances hypothermia-induced neuroprotection and extends the treatment window after stroke. Because both treatments are already known to be clinically feasible and safe, such a strategy would appear have merits for the treatment of acute stroke.
ISSN
0022-510X (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18768189

http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6T06-4TBVPYN-1-9&_cdi=4854&_user=168665&_orig=search&_coverDate=12%2F15%2F2008&_sk=997249998&view=c&wchp=dGLzVtb-zSkzS&md5=533a4b6f91f239697bab09d0878ab0f2&ie=/sdarticle.pdf

http://hdl.handle.net/10371/68405
DOI
https://doi.org/10.1016/j.jns.2008.07.029
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Neurology (신경과학교실)Journal Papers (저널논문_신경과학교실)
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