title: Hibernation-like state induced by an opioid peptide protects against experimental stroke.
abstract: BACKGROUND
  Delta opioid peptide [D-ala2,D-leU5]enkephalin (DADLE) induces hibernation in summer ground squirrels, and enhances preservation and survival of isolated or transplanted lungs and hearts. In the present study, we investigated the protective effect of DADLE in the central nervous system.
  
  
  RESULTS
  Adult Sprague-Dawley rats were pretreated with DADLE (4 mg/kg every 2 h x 4 injections, i.p.) or saline prior to unilateral occlusion of the middle cerebral artery (MCA). Daily behavioral tests revealed that ischemic animals treated with DADLE did not show any significant behavioral dysfunctions compared with saline-treated ischemic animals. Opioid antagonists only transiently inhibited the protective effect of DADLE, indicating the participation of non-opioid mechanisms in DADLE neuroprotection. Histological examination using triphenyltetrazolium chloride (TTC) revealed that brains from ischemic animals treated with DADLE, either alone or with adjuvant opioid blockers, exhibited almost completely intact striata. In contrast, brains from ischemic animals that received saline showed significant infarction in the lateral striatum. Analyses of apoptotic cell death revealed a significant increase in the p-53 mRNA expression in the striatum of ischemic animals that received saline, while those that received DADLE exhibited near normal striatal p-53 expression. This protective effect was accompanied by significant increments in protein levels of glial cell line-derived neurotrophic factor in the striatum of DADLE-treated ischemic animals.
  
  
  CONCLUSIONS
  These results indicate that DADLE protected against necrotic and apoptotic cell death processes associated with ischemia-reperfusion injury. The present study demonstrates that delta opioids are crucially involved in stroke, suggesting that the opioid system is important in the study of brain injury and protection.
authors.affiliation: National Institutes of Health, National Institute on Drug Abuse Intramural Research Program, Cellular Neurobiology Branch, Baltimore, MD, USA. cborlong@health.usf.edu
authors.forename: Cesar V
authors.initials: CV
authors.lastname: Borlongan
authors.forename: Teruo
authors.initials: T
authors.lastname: Hayashi
authors.forename: Peter R
authors.initials: PR
authors.lastname: Oeltgen
authors.forename: Tsung-Ping
authors.initials: TP
authors.lastname: Su
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000187:drug effects*; D020520:Brain Infarction / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002545:Brain Ischemia / Q000188:drug therapy; D004195:Disease Models, Animal; D016308:Enkephalin, Leucine-2-Alanine / Q000627:therapeutic use*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D006605:Hibernation / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D016308:Enkephalin, Leucine-2-Alanine