title: Delta opioid peptide [D-Ala2, D-Leu5] enkephalin (DADLE) triggers postconditioning against transient forebrain ischemia.
abstract: Preconditioning with selective delta opioid peptide [d-Ala2, d-Leu5] enkephalin (DADLE) provides ischemic tolerance following transient forebrain ischemia in rats. However, whether DADLE postconditioning retains its neuroprotective efficacy and the underlying molecular mechanism in ischemic brain is largely unknown. We investigated DADLE postconditioning protection of hippocampal CA1 neurons against transient forebrain ischemia. 6 days after being implanted with cannula at the right lateral ventricle, rats underwent 10 min of forebrain ischemia by four vessel occlusion. Hippocampal CA1 neuronal survival and degeneration were measured in the hippocampi of rats at 3 days after ischemia. The behavioral and cognitive improvements of DADLE treatment in rats were also evaluated on days 5-9 using open-field and Morris water maze tests. The results showed that DADLE at doses of 0.25 and 2.5 nmol, but not 25 nmol, could significantly protect CA1 neurons against ischemia/reperfusion injury. Co-administration with the delta-opioid receptor antagonist naltrindole or pretreatment with the Akt antagonist LY294002 completely abolished the DADLE postconditioning effect. Furthermore, DADLE postconditioning exhibited cognitive benefits in rats with transient forebrain ischemia. The study thus suggested a therapeutic opportunity of postconditioning neuroprotection by DADLE and also provided important information in understanding the mechanism of DADLE action in the ischemic brain.
authors.affiliation: Department of Anesthesiology, RenJi Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Shuyan
authors.initials: S
authors.lastname: Wang
authors.forename: Yale
authors.initials: Y
authors.lastname: Duan
authors.forename: Diansan
authors.initials: D
authors.lastname: Su
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.forename: Juan
authors.initials: J
authors.lastname: Tan
authors.forename: Danqing
authors.initials: D
authors.lastname: Yang
authors.forename: Weili
authors.initials: W
authors.lastname: Wang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhao
authors.forename: Xiangrui
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology*; D006624:Hippocampus / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D057775:Ischemic Postconditioning / Q000379:methods*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D016548:Prosencephalon / Q000098:blood supply* / Q000187:drug effects* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018696:Neuroprotective Agents; D016308:Enkephalin, Leucine-2-Alanine; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt