2005 Fiscal Year Final Research Report Summary
Study for mitochondrial permeability transition in delayed cerebral energy failure induced by transient intrauterine ischemia in the immature rat
| Project/Area Number |
15591783
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Nippon Medical School |
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Principal Investigator |
NAKAI Akihito Nippon Medical School, Department of Medicine, Associate Professor, 医学部, 助教授 (20227721)
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| Co-Investigator(Kenkyū-buntansha) |
TANIUCHI Yoshinari Nippon Medical School, Department of Medicine, Research Associate, 医学部, 助手 (20318512)
OKUDA Naotaka Nippon Medical School, Department of Medicine, Research Associate, 医学部, 助手 (00366759)
MIYAKE Hidehiko Nippon Medical School, Department of Medicine, Research Associate, 医学部, 助手 (40297932)
YOKOTA Akishige Nippon Medical School, Department of Medicine, Assistant Professor, 医学部, 講師 (80287763)
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| Project Period (FY) |
2003 – 2005
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| Keywords | Mitochondria / Permeability transition / Ultrastructure / Fetal brain damage |
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| Research Abstract |
Recirculation following 30 minutes of intrauterine ischemia due to uterine artery occlusion has previously been found to be accompanied with 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 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 fetal rat brain were examined at the end of 30 minutes of intrauterine ischemia and after 1, 2, 3 and 4 hours of recirculation. Cyclosporin A (CsA), a potent and virtually 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 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 CsA. The present study indicates that CsA treatment improves recovery of fetal brain energy metabolism and inhibits the mitochondrial swelling following transient intrauterine ischemia. The results suggest that mitochondria and MPT may be involved in the development of ischemic brain damage in the immature rat.
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