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Study on the role of nitric oxide in hypoxic-ischemic brain injury

Research Project

Project/Area Number 07670863
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionKobe University

Principal Investigator

YONETANI Masahiko  Kobe University, School of Medicine, Assistant, 医学部, 助手 (60221678)

Co-Investigator(Kenkyū-buntansha) HAJIME Nakamura  Kobe University, School of Medicine, Professor, 医学部, 教授 (40030978)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1995: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsNitric oxide / Hypoxia / Dopamine / Newborn / Striatum / ドパミン代謝
Research Abstract

The present study tests the hypothesis that nitric oxide (NO) will modulate the metabolic responses of the striatal dopaminergic system during hypoxia in newborn. The study was carried out in urethaneanesthetized 7-day-old rats using in vivo microdialysis. Following baseline, rats underwent 60-min hypoxia in 8% O2 and the subsequent 60-min recovery (21% O2). The rats were randomized prior to hypoxia into 3 treatment groups. One group received L-arginine via microdialysis probe at a concentration of 100 muM.Another group received an inhibitor of NO synthase, N-nitro-L-arginine methyl ester (L-NAME) at 100 muM.Treatment was administered from 30 min before hypoxia to the end of hypoxia. The control group received normal Ringer's solution throughout the experiment. Samples were collected at 10 min intervals and dialysate dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were studied. In control, DA level increased to 241(]SY.+-。[)37% of baseline by the end of hy … More poxia. DOPAC and HVA levels decreased by 48(]SY.+-。[)3% and 59(]SY.+-。[)4% respectively. Local application of L-arginine or L-NAME alone did not induce significant changes in the basal extracellular dopamine, DOPAC and HVA levels. In L-NAME treated group, maximal increase of DA level induced by hypoxia (142(]SY.+-。[)24%) was significantly lower than those in both control and L-arginine treated group (p<0.05). L-Arginine treated group showed similar increase of dopamine compared to the controls. Treatment with L-NAME also attenuated the accumulation of extracellular dopamine in striatum induced by by high K-depolarization (L-NAME ; 603(]SY.+-。[)116% vs. control : 1,410(]SY.+-。[)307% of spontaneous baseline level, p<0.05). Thses results indicate that inhibition of NO synthesis attenuates hypoxia-induced increase of striatal extracellular DA and may prevent hypoxic injury by reducing oxygen radicals generation from the oxidation of DA.Inhibition of NO synthesis may prevent hypoxic neuronal injury by inhibiting striatal dopamine release and reducing reactive oxygen species which are generated through the oxidation of dopamine. Less

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (9 results)

All Other

All Publications (9 results)

  • [Publications] 中村 肇: "新生児脳障害予防への戦略" 日本未熟児新生児学会誌. 8. 1-5 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 米谷昌彦: "新生児脳障害の成因と予後-NOの関与" 脳と発達. 28. 125-127 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 米谷昌彦: "発達期脳の一過性低酸素負荷に対するNOの動態について" 日本新生児学会誌. 33(印刷中). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Masahiko Yonetani: "The role of nitric oxide in hypoxic-ischemic injury" No To Hattatsu. 28 (2). 125-127 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hajime Nakamura: "Strategy for the prevention of neonatal brain injury." Journal of Japan Society for Premature and Newborn Medicine. 8 (1). 1-5 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Masahiko Yonetani: "The alteration of nitric oxide level during transient hypoxia in developing rat brain." Acta Neonatologica Japonica. 33 (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 中村肇: "新生児脳障害予防への戦略" 日本未熟児新生児学会誌. 8. 1-5 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 米谷昌彦: "新生児脳障害の成因と予後-NOの関与" 脳と発達. 28. 125-127 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 米谷昌彦: "発達基脳の一過性低酸素負荷に対するNOの動態について" 日本新生児学会誌. 33. (印刷中) (1997)

    • Related Report
      1996 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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