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Study on the characteristic plasticity and preventive mechanisms against neonatal brain damage.

Research Project

Project/Area Number 09470241
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

NAKAMURA Hajime  Kobe University School of Medicine, Professor, 医学部, 教授 (40030978)

Co-Investigator(Kenkyū-buntansha) SOMA Osamu  Kobe University School of Medicine, Assistant Professor, 医学部・附属病院, 助手 (70283893)
TSUNEISHI Syuichi  Kobe University School of Medicine, Assistant Professor, 医学部・附属病院, 助手 (10271040)
YONETANI Masahiko  Kobe University School of Medicine, Assistant Professor, 医学部, 助手 (60221678)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥12,200,000 (Direct Cost: ¥12,200,000)
Fiscal Year 1998: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1997: ¥8,600,000 (Direct Cost: ¥8,600,000)
Keywordshypoxia / ischemia / brain damage / neonate / heme oxygenase-1
Research Abstract

Heme oxygenase-1 (HO-1) is an inducible enzyme in heme catabolism that cleaves heme to form biliverdin, carbon monoxide and iron. Although HO-1 is only expressed at a basal level in the normal rodent brain, the expression of HO-1 is strongly activated response to various stumuli. We investigated the quantitative changes in HO-1 mRNA and protein levels in 7-day-old rat model of hypoxic-ischemic (HI) brain damage. The amount of HO-1 protein was the highest on the ligated side of the hippocampus, and it increased to a maximum at 12 hrs following HI insult. The level of HO-1 mRNA had already increased by the end of HI, reached a maximum at 3 hrs following HI insult and then decreased. The time course of the HO-1 protein induction was essentially consistent with that of HO-1 mRNA.In the newborn hypoxic-ischemic rat model, the expression of HO-1 is induced at an earlier stage compared to that in the adult ischemic rat model. 158
To clarify the biological effects of HO-1 against developing brain cells, we analyzed the influence of HO-1 induced by heat shock treatment (42 degree, 30 min) on glial differentiation. Rat glioma cell line, C6, can express both proteolipid protein (PLP) with retinoic acid treatment and glial fibrillary acidic protein (GFAP) with dbcAMP treatment. Heat shock treatment suppressed PLP expression and enhanced GFAP expression in C6 cells. Heat shock proteins, including HO-1, may interfere the glial differentiation resulting in perinatal white matter lesion.
Defense mechanism of HO-1 against oxidative stress begins to work at the early stages of HI insult in the vulnerable perinatal brain and may contribute to protect against brain damage resulting from a combination of hypoxia and ischemia during the perinatal period. However, induced heat shock proteins may affect the glial differentiation leading to white matter lesion.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (4 results)

All Other

All Publications (4 results)

  • [Publications] Nabetani M,Koterazawa K,Miyata H,Takada S,Uetani Y,Kodama S,Nakamura H.: "MRI studies in spastic cerebral palsy of preterm delivery and comparison between the volumes of white matter of occipital lobe and degree of motor impairment." The Journal of the Japan Pediatric Society. 102 (4). 439-443 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takada S,Nakamura H.: "Hypoxic-ischemic encephalopathy of the newborn." Journal of Clinical Rehabilitation. 7 (1). 81-86 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Taguchi K,Soma O,Tsuneishi S,Takada S,Nakamura H.: "Transient induction of heme oxygenase-1 on hypoxic-ischemic brain damage in the neonate rat." Brain and Development in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ioroi T, Yonetani M, Nakamura H.: "Effects of hypoxia and reoxygenation on nitric oxide production and cerebral blood flow in developing rat striatum" Pediatric Research. 43・6. (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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