title: delta-Opioid receptor activation attenuates oxidative injury in the ischemic rat brain.
abstract: BACKGROUND
  We have recently shown that delta-opioid receptors (DORs) play an important role in neuroprotection from hypoxic injury via the regulation of extracellular signaling-regulated kinase (ERK) and cytochrome c release. Since ERK and cytochrome c are differentially involved in caspase signaling of oxidative injury that significantly contributes to neuronal damage in ischemia/reperfusion, we considered if DOR activation protects the ischemic brain by attenuating oxidative injury.
  
  
  RESULTS
  We observed that, in a model of cerebral ischemia with middle cerebral artery occlusion, DOR activation increased the activity of major antioxidant enzymes, glutathione peroxidase and superoxide dismutase, and decreased malondialdehyde and nitric oxide levels in the cortex exposed to cerebral ischemia/reperfusion. In addition, DOR activation reduced caspase 3 expression, though it did not significantly affect the increase in interleukin (IL)1beta and tumor necrosis factor (TNF)alpha expression at the same timepoint. PD98059, an inhibitor of mitogen-activated protein kinase (MAPK) extracellular signaling-regulated kinase kinase, accelerated animal death during ischemia/reperfusion.
  
  
  CONCLUSIONS
  DOR activation attenuates oxidative injury in the brain exposed to ischemia/reperfusion by enhancing antioxidant ability and inhibiting caspase activity, which provides novel insights into the mechanism of DOR neuroprotection.
authors.affiliation: Third Clinical College of Schoow University, Changzhou, Jiangsu, PR China. bigyang@vip.sina.com
authors.forename: Yilin
authors.initials: Y
authors.lastname: Yang
authors.forename: Xiwei
authors.initials: X
authors.lastname: Xia
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Lu
authors.initials: L
authors.lastname: Li
authors.forename: Guanghua
authors.initials: G
authors.lastname: Luo
authors.forename: Ying
authors.initials: Y
authors.lastname: Xia
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000378:metabolism*; D015427:Reperfusion Injury / Q000150:complications / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D012333:RNA, Messenger; D017465:Receptors, Opioid, delta; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D008315:Malondialdehyde; D016308:Enkephalin, Leucine-2-Alanine; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D053148:Caspase 3