Sevoflurane Improves Hemorrhagic Shock and Resuscitation-Induced Cognitive Impairments and Mitochondrial Dysfunctions through SIRT1-Mediated Autophagy.

Abstract

Cerebral ischemia reperfusion injury (IRI) induced by hemorrhagic shock and reperfusion (HSR) is the main cause of death following trauma. Previous studies indicated the neuroprotective effect of sevoflurane postconditioning (SP) in cerebral IRI. However, the mechanisms still remain elusive. Cerebral IRI models with SP were established by using HSR with C57BL/6 mice (male, 3-month-old) in vivo and by using oxygen glucose deprivation and reoxygenation (OGD/R) with HT22 cells in vitro. Postoperative cognition was evaluated by the Morris water maze, novel object recognition, and elevated plus maze tests. The role of SIRT1 was determined by using siRNA, a sensitive inhibitor (EX527), or an overexpression shRNA-GFP lentivirus. IRI caused significant disabilities of spatial learning and memory associated with enhanced cerebral infarct and neuronal apoptosis, which were effectively attenuated by SP. IRI also made a significant decrease of SIRT1 accompanied by oxidative stress, mitochondria dysfunction, and inactivated autophagy. SP or genetically overexpressing SIRT1 significantly suppressed defective autophagy, mitochondrial oxidative injury, and neuronal death caused by HSR or OGD/R. However, genetic suppression or pharmacological inhibition of SIRT1 significantly reversed the impact of SP treatment on mitochondrial DNA transcription ability and autophagy. Our results demonstrate that the loss of SIRT1 causes a sequential chain of mitochondrial dysfunction, defective autophagy, and neuronal apoptosis after IRI in the preclinical stroke models. Sevoflurane postconditioning treatment could effectively attenuate pathophysiological signatures induced by noxious stimuli, which maybe mediated by SIRT1.

• Authors: Jianwei Shu, Xiaotong Huang, Qizhi Liao, Jianan Wang, Yuqi Zhou, Yihuan Chen, Ming Chen, Cheng Qian, Ye Zhang, Xianwen Hu, Chunxia Huang
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2022 Pg. 9771743 ( 2022) ISSN: 1942-0994 [Electronic] United States
• PMID: 35528522 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Jianwei Shu et al.

Chemical References

• Sevoflurane
• Sirt1 protein, mouse
• Sirtuin 1

Topics

• Animals
• Apoptosis
• Autophagy
• Cognitive Dysfunction (complications, drug therapy)
• Male
• Mice
• Mice, Inbred C57BL
• Mitochondria
• Reperfusion Injury (complications, drug therapy)
• Sevoflurane (pharmacology)
• Shock, Hemorrhagic (complications, drug therapy)
• Sirtuin 1