title: Acyl Ghrelin Improves Synapse Recovery in an In Vitro Model of Postanoxic Encephalopathy.
abstract: Comatose patients after cardiac arrest have a poor prognosis. Approximately half never awakes as a result of severe diffuse postanoxic encephalopathy. Several neuroprotective agents have been tested, however without significant effect. In the present study, we used cultured neuronal networks as a model system to study the general synaptic damage caused by temporary severe hypoxia and the possibility to restrict it by ghrelin treatment. Briefly, we applied hypoxia (pO2lowered from 150 to 20 mmHg) during 6 h in 55 cultures. Three hours after restoration of normoxia, half of the cultures were treated with ghrelin for 24 h, while the other, non-supplemented, were used as a control. All cultures were processed immunocytochemically for detection of the synaptic marker synaptophysin. We observed that hypoxia led to drastic decline of the number of synapses, followed by some recovery after return to normoxia, but still below the prehypoxic level. Additionally, synaptic vulnerability was selective: large- and small-sized neurons were more susceptible to synaptic damage than the medium-sized ones. Ghrelin treatment significantly increased the synapse density, as compared with the non-treated controls or with the prehypoxic period. The effect was detected in all neuronal subtypes. In conclusion, exogenous ghrelin has a robust impact on the recovery of cortical synapses after hypoxia. It raises the possibility that ghrelin or its analogs may have a therapeutic potential for treatment of postanoxic encephalopathy.
authors.affiliation: Department of Clinical Neurophysiology, Faculty of Science and Technology, University of Twente, Building Carré 3714, P.O. Box 217, 7500 AE, Enschede, The Netherlands. stoyanovai@yahoo.co.uk.
authors.forename: Irina I
authors.initials: II
authors.lastname: Stoyanova
authors.affiliation: Department of Clinical Neurophysiology, Faculty of Science and Technology, University of Twente, Building Carré 3714, P.O. Box 217, 7500 AE, Enschede, The Netherlands.|Department of Neurology, Rijnstate Hospital, Arnhem, The Netherlands.
authors.forename: Jeannette
authors.initials: J
authors.lastname: Hofmeijer
authors.affiliation: Department of Clinical Neurophysiology, Faculty of Science and Technology, University of Twente, Building Carré 3714, P.O. Box 217, 7500 AE, Enschede, The Netherlands.|Department of Clinical Neurophysiology, Medisch Spectrum Twente, Enschede, The Netherlands.
authors.forename: Michel J A M
authors.initials: MJAM
authors.lastname: van Putten
authors.affiliation: Department of Clinical Neurophysiology, Faculty of Science and Technology, University of Twente, Building Carré 3714, P.O. Box 217, 7500 AE, Enschede, The Netherlands.|Department of Biomedical Signals and Systems, EWI, University of Twente, Enschede, The Netherlands.
authors.forename: Joost
authors.initials: J
authors.lastname: le Feber
mesh_terms: D000818:Animals; D001927:Brain Diseases / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D048429:Cell Size; D054439:Ghrelin / Q000494:pharmacology / Q000627:therapeutic use*; D000860:Hypoxia / Q000150:complications* / Q000473:pathology; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017208:Rats, Wistar; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D054439:Ghrelin; D016708:Synaptophysin
keywords: Brain hypoxia; Ghrelin; Postanoxic encephalopathy; Synapse density