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Research for the pathogenesis of perinatal brain damage and it's protection

Research Project

Project/Area Number 11307032
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionOsaka University

Principal Investigator

MURATA Yuji  Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (40283759)

Co-Investigator(Kenkyū-buntansha) FUJII Eriko  Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (70231561)
OHMICHI Masahide  Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (10283764)
KANZAKI Toru  Osaka University, Graduate School of Medicine, AssociateProfessor, 医学系研究科, 助教授 (00263278)
FUKUDA Hirotsugu  Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (40324751)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥32,090,000 (Direct Cost: ¥30,200,000、Indirect Cost: ¥1,890,000)
Fiscal Year 2001: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Fiscal Year 2000: ¥8,400,000 (Direct Cost: ¥8,400,000)
Fiscal Year 1999: ¥15,500,000 (Direct Cost: ¥15,500,000)
Keywordsbrain damage / hypoxia-ischemia / cord occlusion / cerebral blood flow / hypothermia / apoptosis / 低酸素・虚血性脳症 / 臍帯遮断 / フルクトース / 臍帯オクルージョン / 低酸素脳障害 / 胎仔低血圧 / フリーラジカル
Research Abstract

Seven-day-old rats underwent a combination of left common carotid artery ligation and exposure to 8 % oxygen for 1 hour. During recovery, the body temperature was kept at 37℃ in a control group and was reduced to 30℃ for 24 hours in a hypothermia group.
Histologicaly, right side of the brain was deeply damaged in control group, however in hyprothermia group it was almost normal. Intense caspase-3 activation was observed in the control brains, but this activation was significantly reduced in hypothernmia group. These findings suggest that the inhibition of caspase-3 activation may be an interventional point underlying the neuroprotective effect of hypothermia in neonate.
At 3 months of age, the ABR were performed. In this test, HI animals showed brain stem dysfunction assessed by measuring interpeak latencies for waves III-V and I-V. Hypothermia significantly ameliorated wave V abnormalities. Injury to the ipsilateral inferior colliculus was also reduced in the hypothermia group compared with that in the normothermia group, and the degree of damage assessed histologicallycorrelated well with auditory brainstem response findings. The current study demonstrates that postischemic hypothermias may provide effective and long-lasting neurofunctional as well as histopathologidcal protection to the immature brain.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Fukuda H., Tomimatsu T., Watanabe N., Murata Y., et al.: "Post-ischemic hypothermia blocks caspase-3 activation in the newborn rat brain after hypoxia-ischemia"Brain Resaerch. 910. 187-191 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tomimatsu T., Fukuda H., Endoh M., Murata Y., et al.: "Effects of hypothermia on neonatal hypoxic-ischemic brain injury in the rat : phosphorylation of Akt, activation of caspase-3-lide protease"Neuroscience Letters. 312. 21-24 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tomimatsu T., Fukuda H., Endoh M., Murata Y., et al.: "Effects of neonatal hypoxic-ischemic brain injury on skilled motor tasks and brainstem function in adult rats."Brain Research. 926. 108-117 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mu J., Kanzaki T., Tomimatsu T., Fukuda H., Murata Y., et al.: "Expression of apoptosis in placentae from mice lacking the prostaglandin F receptor"Placenta. 23. 215-223 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Murata Y., Fukuda H., Tomimatsu T., Mu J., et al.: "Cerebral hypothermia as a neuronal rescue strategy"J Obstet Gyne India. 52. 30-34 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mu J., Kanzaki T., Si X., Tomimatsu T., Murata Y., et al.: "Apoptosis and related proteins during parturition in prostaglandin F receptor deficient mice."Biochem Biophys Res Commun. 292. 675-681 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fukuda H., Tomimatsu T., Kanagawa T., Murata Y., et al.: "Postischemic hypothermia induced caspase-3 activation in the newborn rat brain after hypoxia-ischemia and exacerbated the brain damage"Biol Neonate. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tomimatsu T., Fukuda H., Kanagawa T., Murata Y., et al.: "Effects of hyperthermia on hypoxic-ischemic brain damage in the immature rat : its influence on caspase-3-like protease"Am J Obstst Gynecol. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mu J., Kanzaki T., Si X., Fukuda, H., Murata Y., et al.: "Apoptosis and related proteins in placenta of intrauterine fetal death in prostaglandin F receptor-deficient mice."Biology of reproduction. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tomimatsu T., Fukuda H., Endoh M., Murata Y., et al.: "Long-term neuroprotective effects of hypothermia on neonatal hypoxicischemic brain injury in rats, assessed by auditory brainstem response"Pediatr Res. 53. 57-61 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fukuda H., Tomimatsu T., Murata Y. et al.: "Post-ischemic hypothermia blocks caspase-3 activation in the newborn rat brain aftger hypoxia-ischemia"Brain Research. 910. 187-191 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tomimatsu T., Fukuda H., Endoh M., Murata Y., et al.: "Effects of hypothermia on neonatal hypoxic-ischemic brain injury in the rat : phosphorylation of Akt, activation of caspase-3-lide protease"Neuroscience Letters. 312. 21-24 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tomimatsu T., Fukuda H., Endoh M., Murata Y., et al.: "Effects of neonatal hypoxic-ischemic brain injury on skilled motor tasks and brainstem function in adult rats"Brain Research. 926. 108-117 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mu J., Kanzaki T., Tomimatsu T., Murata Y., et al.: "Expression of apoptosis in placentae from mice lacking the prostaglandin F receptor"Placenta. 21. 215-223 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Murata Y., Fukuda H., Tomimatsu T., Mu J., et al.: "Cerebral hypothermia as a neuronal rescue strategy"J Obstet Gynecol India. 52. 30-31 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mu J., Kanzaki T., Si X., Murata Y., et al.: "75-681 Apoptosis and related proteins during parturition in prostaglandin F receptor deficient mice"Biochemical Biophys Res Commun. 292. 6 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tomimatsu T., Fukuda H., Endoh M., Murata Y., et al.: "Long-term neuroprotective effects of hypothermia on neonatal hypoxic- ischemic brain injury in rats, assessed by auditory brainstem response"Pediatr Res. 53. 57-61 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fukuda H., Tomimatsu T., Murata Y. et al.: "Postischemic hypothermia induced caspase-3 activation in the newborn rat brain after hypoxia-ischemia and exacerbated the brain damage"Bio Neonate. (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tomimatsu T., Fukuda H., Murata Y., et al.: "Effects of hyperthermia on hypoxic-ischemic brain damage in the immature rat : its influence on caspase-3-like protease"Am J Obstet Gynecol. (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mu J., Kanzaki T., Si X., Murata Y., et al.: "Apoptosis and related proteins in placenta of intrauterine fetal death in prostaglandin F receptor-deficient mice"Biology of Reproduction. (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fukuda, H.Endo, M.Fujii, E.Kanzaki, T.Murata, Y.: "Post-ischemic hypothermia blocks caspase-3 activation in the newborn rat brain after hypoxia-ischemia"Brain Resaerch. 910. 187-191 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tomimatsu, T.Fukuda, H.Mu, J.Fujii, E.Kanzaki, T.: "Effects of hypothermia on neonatal hypoxic-ischemic brain injury in the rat : phosphorylation of Akt, activation of caspase-3-lide protease"Neuroscience Letters. 312. 21-24 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] K.Masahara,M.Ohmichi,H.Kurachi,K.Tasaka,T.Kanzaki,A.Kimura,J.Hayakawa,K,Hisamoto: "Involvement of extracellular signal-regultaiton protein kinase in gliosis induced during recovery from metabolic inhibition"Biochemical Biophysical Res Commun. 267. 892-896 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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