title: 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.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Shaanxi Province, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.forename: Li
authors.initials: L
authors.lastname: Tong
authors.forename: Qi
authors.initials: Q
authors.lastname: Luan
authors.forename: Jiao
authors.initials: J
authors.lastname: Deng
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Zhaoju
authors.initials: Z
authors.lastname: Li
authors.forename: Hailong
authors.initials: H
authors.lastname: Dong
authors.forename: Lize
authors.initials: L
authors.lastname: Xiong
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D017209:Apoptosis; D001927:Brain Diseases; D003652:Decanoic Acids / Q000494:pharmacology; D006880:Hydroxy Acids / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000473:pathology; D019194:Ischemic Preconditioning; D008297:Male; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors
chemical_list: D000889:Anti-Arrhythmia Agents; D003652:Decanoic Acids; D006880:Hydroxy Acids; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C052853:5-hydroxydecanoic acid