title: Role of mitochondrial permeability transition in fetal brain damage in rats.
abstract: Recirculation after transient in utero ischemia has previously been found to be accompanied by delayed deterioration of cellular bioenergetic state and of mitochondrial function in the fetal rat brain. Our objective was to assess whether the delayed deterioration is a result of the activation of mitochondrial permeability transition which is observed ultrastructurally as mitochondrial swelling. The respiratory activities and ultrastructure of isolated mitochondria and the cellular bioenergetic state in fetal rat brain were examined at the end of 30 minutes of in utero ischemia and after 1, 2, 3 and 4 hours of recirculation. Cyclosporin A, a potent and virtually specific mitochondrial permeability transition blocker, or vehicle was administered 1 hour after recirculation. In the vehicle-treated animals, the transient ischemia was associated with a delayed deterioration of cellular bioenergetic state and mitochondrial activities at 4 hours of recirculation. The number of swollen mitochondria increased markedly after 4 hours of recirculation. The deterioration and the swelling were prevented by cyclosporin A. The present study indicates that cyclosporin A treatment improves recovery of fetal brain energy metabolism and inhibits the mitochondrial swelling after transient in utero ischemia. The results suggest that mitochondria and mitochondrial permeability transition may be involved in the development of ischemic brain damage in the immature rat.
authors.affiliation: Department of Obstetrics and Gynecology, Nippon Medical School, Tokyo, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Nakai
authors.forename: Yukino
authors.initials: Y
authors.lastname: Shibazaki
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Taniuchi
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Miyake
authors.forename: Atsuko
authors.initials: A
authors.lastname: Oya
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takeshita
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001925:Brain Damage, Chronic / Q000196:embryology* / Q000473:pathology; D002545:Brain Ischemia / Q000196:embryology* / Q000473:pathology; D002540:Cerebral Cortex / Q000098:blood supply / Q000196:embryology / Q000473:pathology; D016572:Cyclosporine / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D005260:Female; D005311:Fetal Hypoxia / Q000196:embryology* / Q000473:pathology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D008933:Mitochondrial Swelling / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000196:embryology / Q000473:pathology
chemical_list: D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D016572:Cyclosporine