On behalf: Center for Molecular Cardiology

Citation:

Cardiovascular Research Supplements ( 2016 ) 111 ( S1 ), S67

Background: Ischemic stroke is one of the leading causes of mortality and morbidity in industrialized countries and, due to the progressively aging population, its incidence is predicted to increase further. Sirtuin 5 (SIRT5) protects from ischemia/ reperfusion injury in the heart (Boylston et al 2015),however, whether SIRT5 displays similar properties in ischemia/reperfusion-induced brain injury still remains unknown.

Aim (s) or purpose: To investigate the role of sirtuin 5 (SIRT5) in a murine model of cerebral ischaemia-reperfusion (IR) induced by middle cerebral artery occlusion (MCAO).

Design & methods: Male 12- to 14-week old C57/B6 mice were randomly divided into SIRT5 siRNA (siSIRT5) or scrambled siRNA control (siSCR) treated groups and subjected to transient middle cerebral artery occlusion (MCAO) for 45min followed by 24h of reperfusion. Knockdown of SIRT5 was performed 24h before MCAO using small interfering RNA. Final infarct volumes were analyzed by TTC (2,3,5-triphenyl-2H-tetrazolium chloride) staining at 24h after ischemia. Neurological deficit was determined by Bederson index and rotarod performance test at 2h, 24h and 48h post-MCAO.

Results: siSIRT5 treated mice displayed smaller infarct volumes compared to siSCR (24.15 ± 2.61 vs. 31.2 ± 1.50 % p=0.03, Figure 1). In line with the above, siSIRT5 mice demonstrated blunted neurological deficit as compared to siSCR at 48h post-MCAO as assessed by the Bederson index (0.68 ± 0.17 vs. 1.27 ± 0.19 AU, p= 0.036). In addition, there was a tendency for increased latency to fall in the rotarod test in siSIRT5 compared with siSCR (81.33± 5.21 vs. 69.00 ± 6.21 s, NS, data not shown) nonetheless, this difference did not reach statistical significance.

Conclusions: Knockdown of SIRT5 improves stroke outcome including stroke size and neurological deficit in mice indicating a deleterious role of this histone deacetylase in these experimental settings. Additional experiments will be performed to elucidate the underlying mechanisms of this effect.

Sirtuin 5 mediates brain injury in a mouse model of cerebral ischemia-reperfusion

Abstract

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Miss Candela Diaz-Canestro

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Poster session 2 - Oxygen sensing, ischaemia and reperfusion

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Frontiers in CardioVascular Biology 2016