期刊
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
卷 34, 期 2, 页码 284-287出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/jcbfm.2013.195
关键词
ApoE knockout; distal middle cerebral artery occlusion; fasudil; hydroxyfasudil; hyperlipidemia; laser speckle flowmetry
资金
- National Institutes of Health [NS055104, NS061505, NS33335]
- Basic Science Research Program through the National Research Foundation (NRF) of Korea
- Ministry of Education, Science and Technology [2010-0007470]
- Andrew David Heitman Foundation
- The Ellison Foundation
- National Research Foundation of Korea [2010-0007470] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Hyperlipidemia is a major cardiovascular risk factor associated with progressive cerebrovascular dysfunction and diminished collateral perfusion in stroke. Rho-associated kinase (ROCK) may be an important mediator of hyperlipidemic vascular dysfunction. We tested the efficacy of acute or chronic ROCK inhibition on the size of dynamic perfusion defect using laser speckle flowmetry in hyperlipidemic apolipoprotein E knockout mice fed on a high-fat diet for 8 weeks. Mice were studied at an age before the development of flow-limiting atherosclerotic stenoses in aorta and major cervical arteries. Focal ischemia was induced by distal middle cerebral artery occlusion (dMCAO) during optical imaging. The ROCK inhibitor fasudil (10 mg/kg) was administered either as a single dose 1 hour before ischemia onset, or daily for 4 weeks. Fasudil decreased both baseline arterial blood pressure and cerebrovascular resistance (CVR) by similar to 15%, and significantly improved tissue perfusion during dMCAO. Interestingly, pen-infarct depolarizations were also reduced. Chronic treatment did not further enhance these benefits compared with acute treatment with a single dose. These data show that ROCK inhibition improves CVR and ischemic tissue perfusion in hyperlipidemic mice.
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