title: Effects of ghrelin on postresuscitation brain injury in a rat model of cardiac arrest.
abstract: Poor neurological outcome remains a major problem in patients with cardiac arrest. Ghrelin has been shown to be neuroprotective in models of neurologic injury in vitro and in vivo. This study was performed to assess the effects of ghrelin on postresuscitation brain injury in a rat model of cardiac arrest. Sprague-Dawley rats were subjected to 6-min cardiac arrest and resuscitated successfully. Either vehicle (saline) or ghrelin (80 μg/kg) was injected blindly immediately after return of spontaneous circulation (ROSC). A tape removal test was performed to evaluate neurological function at 24, 48, and 72 h after ROSC. Then, brain tissues were harvested and coronal brain sections were analyzed by hematoxylin and eosin (HE) staining for neuronal viability and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining for apoptosis in hippocampal CA1 sectors. In additional groups, rats were sacrificed at 6 h after ROSC, and hippocampal tissues were collected for further analysis. We found that animals treated with ghrelin had improved neurological performances, reduced neuronal injury, and inhibited neuronal apoptosis compared with the vehicle group. Moreover, ghrelin treatment was associated with the following: (1) a decrease in caspase-3 up-regulation and an increased Bcl-2/Bax ratio, (2) a reduction in maleic dialdehyde content and an up-regulation in superoxide dismutase activity, and (3) an increase in uncoupling protein 2 (UCP-2) expression. Our results suggest that ghrelin treatment attenuated postresuscitation brain injury in rats, possibly via regulation of apoptosis, oxidative stress, and mitochondrial UCP-2 expression. Ghrelin may have therapeutic potential when administered after cardiac arrest and cardiopulmonary resuscitation.
authors.affiliation: Departments of *Emergency, and †Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
authors.forename: Xuemeng
authors.initials: X
authors.lastname: Xie
authors.forename: Jincheng
authors.initials: J
authors.lastname: Zhang
authors.forename: Di
authors.initials: D
authors.lastname: Chen
authors.forename: Hao
authors.initials: H
authors.lastname: Pan
authors.forename: Ziqian
authors.initials: Z
authors.lastname: Wu
authors.forename: Dong
authors.initials: D
authors.lastname: Ge
authors.forename: Guangtian
authors.initials: G
authors.lastname: Yang
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D000818:Animals; D017209:Apoptosis; D001930:Brain Injuries / Q000503:physiopathology* / Q000628:therapy; D056547:CA1 Region, Hippocampal / Q000187:drug effects; D016887:Cardiopulmonary Resuscitation; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival; D054439:Ghrelin / Q000737:chemistry / Q000627:therapeutic use*; D006323:Heart Arrest / Q000503:physiopathology* / Q000628:therapy; D007473:Ion Channels / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D009474:Neurons / Q000473:pathology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000627:therapeutic use; D018384:Oxidative Stress; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D000071246:Uncoupling Protein 2; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000447:Aldehydes; C494828:Bax protein, rat; D054439:Ghrelin; D007473:Ion Channels; D024101:Mitochondrial Proteins; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; D051028:bcl-2-Associated X Protein; C015977:malealdehyde; D013482:Superoxide Dismutase; C505410:Casp3 protein, rat; D053148:Caspase 3