Protective effect of delayed remote limb ischemic postconditioning: role of mitochondrial K(ATP) channels in a rat model of focal cerebral ischemic reperfusion injury.

Abstract

Delayed remote ischemic postconditioning (DRIPost) has been shown to protect the rat brain from ischemic injury. However, extremely short therapeutic time windows hinder its translational use and the mechanism of action remains elusive. Because opening of the mitochondria K(ATP) channel is crucial for cell apoptosis, we hypothesized that the neuroprotective effect of DRIPost may be associated with K(ATP) channels. In the present study, the neuroprotective effects of DRIPost were investigated using adult male Sprague-Dawley rats. Rats were exposed to 90 minutes of middle cerebral artery occlusion followed by 72 hours of reperfusion. Delayed remote ischemic postconditioning was performed with three cycles of bilateral femoral artery occlusion/reperfusion for 5 minutes at 3 or 6 hours after reperfusion. Neurologic deficit scores and infarct volumes were assessed, and cellular apoptosis was monitored by terminal deoxynucleotidyl transferase nick-end labeling. Our results showed that DRIPost applied at 6 hours after reperfusion exerted neuroprotective effects. The K(ATP) opener, diazoxide, protected rat brains from ischemic injury, while the K(ATP) blocker, 5-hydroxydecanote, reversed the neuroprotective effects of DRIPost. These findings indicate that DRIPost reduces focal cerebral ischemic injury and that the neuroprotective effects of DRIPost may be achieved through opening of K(ATP) channels.

• Authors: Jing Sun, Li Tong, Qi Luan, Jiao Deng, Yan Li, Zhaoju Li, Hailong Dong, Lize Xiong
• Journal: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab) Vol. 32 Issue 5 Pg. 851-9 (May 2012) ISSN: 1559-7016 [Electronic] United States
• PMID: 22274742 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Arrhythmia Agents
• Decanoic Acids
• Hydroxy Acids
• Potassium Channel Blockers
• Potassium Channels
• 5-hydroxydecanoic acid

Topics

• Animals
• Anti-Arrhythmia Agents (pharmacology)
• Apoptosis
• Brain Diseases
• Decanoic Acids (pharmacology)
• Hydroxy Acids (pharmacology)
• Infarction, Middle Cerebral Artery (metabolism, pathology)
• Ischemic Preconditioning
• Male
• Potassium Channel Blockers (pharmacology)
• Potassium Channels (metabolism)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (metabolism, pathology, prevention & control)
• Time Factors