Dose-dependent neuroprotection of delta opioid peptide [D-Ala2, D-Leu5] enkephalin in neuronal death and retarded behavior induced by forebrain ischemia in rats.
Cerebral ischemic insult, mainly induced by cardiovascular disease, is one of the most severe neurological diseases in clinical. There's mounting evidence showing that delta opioid agonist [D-Ala2, D-Leu5] enkephalin (DADLE) has a tissue-protective effect. However, whether this property is effective to prevent neuronal death induced by forebrain ischemia is not clear. This study was aimed to investigate whether intracerebroventricular (ICV) administration of DADLE has a neuroprotective effect against forebrain ischemia in rats. We found in our study that administration of DADLE 45 min before forebrain ischemia had significant protective effect against CA1 neuronal lose. Further more, we found that DADLE had a dose-dependent protection for improving behavioral retardation revealed by Morris water maze and motor score test, while naltrindole, the antagonist of delta opioid receptor, partially abolished neuroprotective effect of DADLE, which implicated that both opioid and non-opioid systems are involved in ischemic insults and neuroprotection.
Su
Dian-san
DS
Department of Anesthesiology, RenJi Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Wang
Zhen-hong
ZH
Zheng
Yong-jun
YJ
Zhao
Yan-hua
YH
Wang
Xiang-rui
XR
D000818:Animals; D001522:Behavior, Animal; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology*; D016923:Cell Death / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016308:Enkephalin, Leucine-2-Alanine / Q000008:administration & dosage*; D007276:Injections, Intraventricular; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D016548:Prosencephalon / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D009292:Narcotic Antagonists; D018696:Neuroprotective Agents; D009271:Naltrexone; D016308:Enkephalin, Leucine-2-Alanine; C055382:naltrindole