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Role of Mitochondrial Permeability Transition in the Immature Brain Following Intrauterine Ischemia
Department of Female Reproductive and Developmental Medicine, Graduate School of Medicine, Nippon Medical School
Recirculation following 30 minutes of intrauterine ischemia due to uterine artery occlusion has previously been found to be accompanied by delayed deterioration of the cellular bioenergetic state and of mitochondrial function in the fetal rat brain. The objective of this study was to assess whether the delayed deterioration is due to the activation of mitochondrial permeability transition (MPT), which is observed ultrastructurally as mitochondrial swelling. The respiratory activities and ultrastructure of isolated mitochondria and the cellular bioenergetic state in the fetal rat brain were examined at the end of 30 minutes of intrauterine ischemia and after 1, 2, 3 or 4 hours of recirculation. Cyclosporin A (CsA), a potent and specific MPT blocker, or vehicle was given 1 hour after recirculation. In the vehicle-treated animals, the transient ischemia was associated with a delayed deterioration of the cellular bioenergetic state and mitochondrial activities 4 hours of recirculation. The number of swollen mitochondria increased markedly after 4 hours of recirculation. Both the deterioration and swelling were prevented by CsA. The present study indicates that treatment with CsA improves recovery of energy metabolism and inhibits mitochondrial swelling following transient intrauterine ischemia in the fetal brain. The results suggest that mitochondria and MPT may be involved in the development of ischemic brain damage in the immature rat.
J Nippon Med Sch 2007; 74: 190-201
Keywords
mitochondria, fetal, brain, ischemia
Correspondence to
Akihito Nakai, MD, Ph D, Department of Obstetrics and Gynecology, Nippon Medical School Tama Nagayama Hospital, 1-7-1 Nagayama, Tama, Tokyo 206-8512, Japan
nakai-3@nms.ac.jp
Received, February 20, 2007
Accepted, March 16, 2007
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