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Role of SIRT1 in Isoflurane Conditioning-Induced Neurovascular Protection against Delayed Cerebral Ischemia Secondary to Subarachnoid Hemorrhage

Authors :
Meizi Liu
Keshav Jayaraman
Tusar Giri
Gregory J. Zipfel
Umeshkumar Athiraman
Source :
International Journal of Molecular Sciences, Vol 22, Iss 8, p 4291 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

We recently reported that isoflurane conditioning provided multifaceted protection against subarachnoid hemorrhage (SAH)-induced delayed cerebral ischemia (DCI), and this protection was through the upregulation of endothelial nitric oxide synthase (eNOS). SIRT1, an NAD-dependent deacetylase, was shown to be one of the critical regulators of eNOS. The aim of our current study is to examine the role of SIRT1 in isoflurane conditioning-induced neurovascular protection against SAH-induced DCI. Mice were divided into four groups: sham, SAH, or SAH with isoflurane conditioning (with and without EX-527). Experimental SAH via endovascular perforation was performed. Anesthetic conditioning was performed with isoflurane 2% for 1 h, 1 h after SAH. EX-527, a selective SIRT1 inhibitor, 10 mg/kg was injected intraperitoneally immediately after SAH in the EX-527 group. SIRT1 mRNA expression and activity levels were measured. Vasospasm, microvessel thrombosis, and neurological outcome were assessed. SIRT1 mRNA expression was downregulated, and no difference in SIRT1 activity was noted after isoflurane exposure. Isoflurane conditioning with and without EX-527 attenuated vasospasm, microvessel thrombosis and improved neurological outcomes. Our data validate our previous findings that isoflurane conditioning provides strong protection against both the macro and micro vascular deficits induced by SAH, but this protection is likely not mediated through the SIRT1 pathway.

Details

Language :
English
ISSN :
14220067 and 16616596
Volume :
22
Issue :
8
Database :
Directory of Open Access Journals
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
edsdoj.37fe67722214250ab0a0642c9bad0ed
Document Type :
article
Full Text :
https://doi.org/10.3390/ijms22084291