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SIRT1 attenuates severe ischemic damage by preserving cerebral blood flow

Lookup NU author(s): Professor Raj KalariaORCiD, Dr Masafumi Ihara


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Silent information regulator 2 homolog 1 (SIRT1) is a protein deacetylase that has been reported to suppress neurodegenerative and cardiovascular pathologies in model organisms. We have recently reported that SIRT1 overexpression preserves cerebral blood flow (CBF) after bilateral common carotid artery stenosis (similar to 50% stenosis) by the deacetylation of endothelial nitric oxide synthase. This study was designed to determine whether cerebral SIRT1 expression would be effective in a more severe model of cerebral ischemia caused by bilateral common carotid artery occlusion (BCAO) in vivo. Sirt1-overexpressing (Sirt1-Tg) mice (n=13) and their wild-type littermates (n=17) were subjected to BCAO for 10 min using microaneurysm clips. Temporal CBF changes were measured by laser speckle flowmetry before and 5, 10 min, and 2 h after BCAO. Histological evaluation of hippocampal changes was performed 7 days after BCAO. Histological findings were significantly less severe in Sirt1-Tg mice than in wild-type mice; wild-type mice showed strokes in the hippocampus, whereas Sirt1-Tg mice had minimal hippocampal damage 7 days after BCAO. Consistent with this observation, wild-type mice showed a severe reduction in CBF to similar to 20-25% of the baseline level during BCAO, whereas Sirt1-Tg littermates showed significantly preserved CBF up to 45-50% of the baseline level. Our study provides evidence for the promising role of SIRT1 in protecting against cerebral global ischemia by preserving CBF and restoring the cerebrovascular reserve. Copyright (c) 2015 Wolters Kluwer Health, Inc. All rights reserved.

Publication metadata

Author(s): Hattori Y, Okamoto Y, Nagatsuka K, Takahashi R, Kalaria RN, Kinoshita M, Ihara M

Publication type: Article

Publication status: Published

Journal: NeuroReport

Year: 2015

Volume: 26

Issue: 3

Pages: 113-117

Print publication date: 11/02/2015

ISSN (print): 0959-4965

ISSN (electronic): 1473-558X

Publisher: Lippincott Williams & Wilkins


DOI: 10.1097/WNR.0000000000000308


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Funder referenceFunder name
SENSHIN Medical Research Foundation
Takeda Science Foundation
0605-1Ministry of Health, Labour and Welfare
23390233Ministry of Education, Culture, Sports, Science and Technology
26640034Ministry of Education, Culture, Sports, Science and Technology