title: Propofol post-conditioning induced long-term neuroprotection and reduced internalization of AMPAR GluR2 subunit in a rat model of focal cerebral ischemia/reperfusion.
abstract: We previously reported that propofol (20 mg/kg/h) post-conditioning provided acute (up to 24 h) neuroprotection in rats with transient middle cerebral artery occlusion. In this study, we extend these data by examining long-term protection and exploring underlying mechanisms involving AMPA receptor GluR2 subunit internalization. Rats were treated with propofol 20 mg/kg/h after 60 min of occlusion (beginning of reperfusion for 4 h). Propofol post-conditioning reduced infarct volume and improved spatial memory deficiencies (up to 28 days) induced by ischemia/reperfusion injury. Additionally, Propofol post-conditioning promoted neurogenesis in the dentate gyrus of hippocampus, as measured by bromodeoxyuridine and neuron-specific nuclear protein immunofluorescence-double staining at day 28 after reperfusion. Finally, propofol post-conditioning increased the surface expression of AMPA receptor GluR2 subunit, thus inhibited the internalization of this part until 28 days after stroke. In conclusion, our data suggest that propofol post-conditioning provides long-term protection against focal cerebral ischemia/reperfusion injury in rats. Furthermore, we found that the inhibition of AMPA receptor GluR2 subunit internalization may contributed to this long-term neuroprotection.
authors.affiliation: Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Haiyun
authors.initials: H
authors.lastname: Wang
authors.forename: Mengqiang
authors.initials: M
authors.lastname: Luo
authors.forename: Cui
authors.initials: C
authors.lastname: Li
authors.forename: Guolin
authors.initials: G
authors.lastname: Wang
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D000963:Antimetabolites; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D001973:Bromodeoxyuridine; D003432:Cross-Linking Reagents; D019084:Fluorescent Antibody Technique, Indirect; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000517:prevention & control; D057775:Ischemic Postconditioning; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects; D018696:Neuroprotective Agents; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D013388:Succinimides / Q000737:chemistry
chemical_list: D018686:Anesthetics, Intravenous; D000963:Antimetabolites; D003432:Cross-Linking Reagents; D018696:Neuroprotective Agents; D018091:Receptors, AMPA; D013388:Succinimides; C035760:bis(sulfosuccinimidyl)suberate; D001973:Bromodeoxyuridine; C104722:glutamate receptor ionotropic, AMPA 2; D015742:Propofol