title: TREK1 activation mediates spinal cord ischemic tolerance induced by isoflurane preconditioning in rats.
abstract: The aim of this study is to examine the role of one of the two-pore (2P) domain K(+) channels, TREK (TWIK-related K(+) channels, TREK)-1, mediated neuroprotection on spinal cord afforded by isoflurane preconditioning. In Experiment 1, male Sprague-Dawley rats were randomly assigned to control (Con) group, an isoﬂurane preconditioning (Iso) group, and sham group. Twenty-four hours after the last pretreatment, spinal cord ischemia was induced in Con and Iso groups. Neurobehavioral testing and histopathologic examination were performed after reperfusion. In Experiment 2, the expression of the TREK1 in the spinal cord was assessed by immunohistochemistry, Western blot and real-time polymerase chain reaction. In Experiment 3, Amiloride, a blocker of stretch-sensitive channels, was administered intraperitoneally immediately prior to each isoflurane preconditioning. Iso group showed a significant reductions in motor deficit index as well as increases in the number of normal neurons compared with the Con group. The expression of TREK1 protein and the level of mRNA after ischemia were higher in the rats of the Iso group than those in the Con group. Amiloride pretreatment abolished the protective effects of Iso preconditioning. These finding indicate that isoflurane preconditioning had a neuroprotective effect against spinal cord ischemia reperfusion injury. These effects may be mediated through the TREK1 pathway.
authors.affiliation: Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yin
authors.forename: Binxiao
authors.initials: B
authors.lastname: Su
authors.forename: Haopeng
authors.initials: H
authors.lastname: Zhang
authors.forename: Wenying
authors.initials: W
authors.lastname: Song
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Chen
authors.forename: Xijing
authors.initials: X
authors.lastname: Zhang
authors.forename: Hailong
authors.initials: H
authors.lastname: Dong
authors.forename: Lize
authors.initials: L
authors.lastname: Xiong
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D019194:Ischemic Preconditioning / Q000379:methods*; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control; D013116:Spinal Cord / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D020760:Spinal Cord Ischemia / Q000378:metabolism*
chemical_list: D018685:Anesthetics, Inhalation; D018696:Neuroprotective Agents; D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1; D007530:Isoflurane