title: Platelet-activating factor antagonist (ABT-491) decreases neuronal apoptosis in neonatal rat model of hypoxic ischemic brain injury.
abstract: Hypoxic ischemic brain injury (HIBI) is a common cause of neonatal mortality and morbidity. To date, no study has investigated the role of platelet-activating factor (PAF) antagonists on neuronal apoptosis in neonatal rat model of HIBI. In the present study, we evaluated the effect of a highly potent and selective PAF antagonist (ABT-491) on neuronal apoptosis in neonatal rat model of HIBI. Seven-day-old Wistar rat pups were subjected to right common carotid artery ligation and hypoxia (92% nitrogen and 8% oxygen) for 2 h. They were treated with ABT-491 or saline either immediately before or after hypoxia. In sham group animals, neither ligation, nor hypoxia was performed. Neuronal apoptosis was evaluated by the terminal-transferase mediated dUTP biotin nick-end-labeling (TUNEL) and caspase-3 staining methods. Administration of ABT-491 either before or after hypoxia resulted in significant reduction of the numbers of apoptotic cells in both hemispheres, when compared to saline treatment group. The numbers of apoptotic cells in right hemispheres in all groups were significantly higher than that in the left hemispheres. These results suggested that ABT-491, a highly potent and selective PAF antagonist, administration either before or after hypoxia reduces apoptosis and we propose that ABT-491 may be a novel approach in the treatment of HIBI.
authors.affiliation: Department of Pediatrics, Tarsus Devlet Hastanesi, Mersin, Turkey.
authors.forename: Gulcin
authors.initials: G
authors.lastname: Bozlu
authors.forename: Aytug
authors.initials: A
authors.lastname: Atici
authors.forename: Ali Haydar
authors.initials: AH
authors.lastname: Turhan
authors.forename: Ayse
authors.initials: A
authors.lastname: Polat
authors.forename: Ali
authors.initials: A
authors.lastname: Nayci
authors.forename: Cetin
authors.initials: C
authors.lastname: Okuyaz
authors.forename: Hakan
authors.initials: H
authors.lastname: Taskinlar
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D002452:Cell Count; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000503:physiopathology; D007093:Imidazoles / Q000627:therapeutic use*; D020287:In Situ Nick-End Labeling; D007211:Indoles / Q000627:therapeutic use*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D051381:Rats
chemical_list: D007093:Imidazoles; D007211:Indoles; D010972:Platelet Activating Factor; D053148:Caspase 3; C107116:ABT 491