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2002 Fiscal Year Final Research Report Summary

Treatment of neonatal brain damage through regulation of protease-activatred receptor-1.

Research Project

Project/Area Number 13671137
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Embryonic/Neonatal medicine
Research InstitutionKobe University Hospital

Principal Investigator

TSUNEISHI Syuichi  Kobe University, University Hospital Assistant Professor, 医学部附属病院, 助手 (10271040)

Co-Investigator(Kenkyū-buntansha) YOKOYAMA Naoki  Kobe University, University Hospital Assistant Professor, 医学部附属病院, 助手 (20314487)
YONETANI Masahiko  Kobe University, Graduate School of Medicine Associate Professor, 大学院・医学系研究科, 助教授 (60221678)
Project Period (FY) 2001 – 2002
Keywordshypoxic-ischemic encephalopathy / thrombin / protease-activated receptor-1 / PAR-1 / necrosis / apoptosis / neonatl rat
Research Abstract

The aim of this study is to determine the efficacy of regulation of thrombin protease-activated receptor-1 against neonatal hypoxic-ischemic (HI) brain damage.
Protease-activated receptor-1 (PAR-1) is a key structure in the balance between serine proteases and its inhibitors, and plays an important role in development and plasticity of the developing brain. A unique artificial peptide, TRAP (thrombin receptor activating peptide), which has an amino acid sequence of SFLLRN, can directly activate PAR-1, We investigated the usefulness of TRAP to prevent neuronal cells from the hypoxic-ischemic (HI) insult in the developing rats. The ontogeny of PAR-1 in the developing rat brain showed that PAR-1 is expressed much at birth- P10, which means significant role on the neurogenesis and glial proliferation.
P7 Sprague-Dawley rats were introduced to the HI loading by the combination of left common carotid artery ligation and the exposure to 8% O_2 for 2 hrs. Low dose TRAP (0.5 μg) administration intracerebroventricularly at 2 hrs before HI insult rescued the CA1 hippocampal nerve cells significantly at P14. High dose TRAP (50 μg) did not rescue the viability of CA1 nerve cells hi contrast. Both the saline and TRAP-50μg groups showed clear DNA ladder formation and positive immunostaining against single-stranded DNA in their hippocampal tissue, suggesting the significant presence of apoptotic nerve cell death.
Adequate activation of PAR-1 using TRAP can inhibit the nerve cell loss against the HI insult in the developing rat brain. This effect is in part dependent on anti-apoptotic function of PAR-1 activation. Regulation of PAR-1 in the developing brain can protect nerve and glial cells through modificating their differentiation.

  • Research Products

    (9 results)

All Other

All Publications (9 results)

  • [Publications] Adachi M: "Combination effect of systemic hypothermia and caspase inhibitor administration against hypoxic-ischemic brain damage in neonatal rats"Pediatric Research. 50. 590-595 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Zhang WL: "Induction of heat shock proteins and its effects on glial differentiation in rat C6 glioblastoma cells"Kobe Journal of Medical Sciences. 47. 77-95 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 常石秀市: "神経生理学的アプローチ -VEPを中心に-"脳と発達. 34. 141-146 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 橋本直樹: "発達期ラットの低酸素性虚血性脳障害に対するトロンビン機能的受容体(Protease-activated receptor-1, PAR-1)活性化の効果"神戸大学医学部紀要. 62. 75-83 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 常石秀市: "赤ちゃんにはなぜ脳の可塑性があるの?"周産期医学. 31. 916-918 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Adachi M.: "Combination effect of systemic hypothermia and caspase inhibitor administration against hypoxic-ischemic brain damage in neonatal rats"Pediatric Research. Vol.50. 590-595 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Zhang WL.: "Induction of heat shock proteins and its effects on glial differentiation in rat C6 glioblastoma cells"Kobe Journal of Medical Sciences. Vol.47. 77-95 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsuneishi S.: "Evaluation of the developing human visual system. Using flash-visual evoked potential"No to Hattatsu. Vol.34. 141-146 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hashimoto N.: "Effect of the protease-activated receptor-1 (PAR-1) activation against the hypoxic-ischemic brain damagein developing rat"Kobe Daigaku Igakubu Kiyou. Vol.62. 75-83 (2002)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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