Remote limb ischemic postconditioning protects against cerebral ischemia-reperfusion injury by activating AMPK-dependent autophagy.

Abstract

Remote limb ischemic postconditioning (RIPoC) is a promising adjunct treatment for cerebral ischemia-reperfusion (IR) injury. However, the underlying mechanisms have not been fully elucidated yet. The present study aims to investigate potential involvement and regulatory mechanisms of autophagy in RIPoC treatment against cerebral IR injury in mice. Mice were subjected to 2 h middle cerebral artery occlusion (MCAO) then treated with vehicle, 3-methyladenine (3-MA, an autophagy inhibitor), or compound C (an AMPK inhibitor) at the onset of reperfusion. RIPoC was carried out by 3 cycles of 10-min occlusion-reperfusion of bilateral femoral artery at the beginning of the reperfusion. Infarct volume, neurological score, and brain water content of the mice were assessed after 12 h reperfusion. Autophagy markers, cell apoptosis markers, and AMPK pathway activity were also evaluated. Our results indicated that RIPoC treatment reduced neurological deficits, brain water content, and infarct volume after IR. Meanwhile, RIPoC was proved to induce autophagy and activate AMPK pathway. Furthermore, the RIPoC-induced autophagy and neuroprotection were abolished by 3-MA and partially blocked by compound C. In conclusion, the present study suggests that RIPoC attenuates cerebral IR injury by activating AMPK-dependent autophagy.

• Authors: Hao Guo, Lei Zhao, Bodong Wang, Xia Li, Hao Bai, Haixiao Liu, Liang Yue, Wei Guo, Zhenyuan Bian, Li Gao, Dayun Feng, Yan Qu
• Journal: Brain research bulletin (Brain Res Bull) Vol. 139 Pg. 105-113 (05 2018) ISSN: 1873-2747 [Electronic] United States
• PMID: 29452253 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Atg7 protein, mouse
• Beclin-1
• Map1lc3b protein, mouse
• Microtubule-Associated Proteins
• Sequestosome-1 Protein
• Sqstm1 protein, mouse
• Protein Kinases
• AMP-Activated Protein Kinase Kinases
• Autophagy-Related Protein 7

Topics

• AMP-Activated Protein Kinase Kinases
• Animals
• Autophagy (physiology)
• Autophagy-Related Protein 7 (metabolism)
• Beclin-1 (metabolism)
• Brain Edema (etiology, therapy)
• Disease Models, Animal
• Extremities (physiology)
• In Situ Nick-End Labeling
• Ischemic Postconditioning (methods)
• Male
• Mice
• Microtubule-Associated Proteins
• Neurologic Examination
• Protein Kinases (metabolism)
• Reperfusion Injury (physiopathology, prevention & control)
• Sequestosome-1 Protein (metabolism)
• Signal Transduction (drug effects)