TY - JOUR
T1 - Role of sirt1 in isoflurane conditioning‐induced neurovascular protection against delayed cerebral ischemia secondary to subarachnoid hemorrhage
AU - Liu, Meizi
AU - Jayaraman, Keshav
AU - Giri, Tusar
AU - Zipfel, Gregory J.
AU - Athiraman, Umeshkumar
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/4/2
Y1 - 2021/4/2
N2 - 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.
AB - 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.
KW - Aneurysmal subarachnoid hemorrhage
KW - Delayed cerebral ischemia
KW - Isoflurane conditioning
KW - SIRT1
UR - http://www.scopus.com/inward/record.url?scp=85104453565&partnerID=8YFLogxK
U2 - 10.3390/ijms22084291
DO - 10.3390/ijms22084291
M3 - Article
C2 - 33924243
AN - SCOPUS:85104453565
SN - 1661-6596
VL - 22
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 8
M1 - 4291
ER -