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ROLE OF NITRIC OXIDE IN PATHOGENESIS UNDERLYING ISCHEMIC BRAIN DAMAGE

Research Project

Project/Area Number 05671181
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Cerebral neurosurgery
Research InstitutionSAITMA MEDICAL SCHOOL

Principal Investigator

MATSUI Toru  SAITAMA MEDICAL SCHOOL,LECTURER, 医学部, 講師 (70199735)

Co-Investigator(Kenkyū-buntansha) ISHIKAWA Toshiro  SAITAMA MEDICAL SCHOOL,ASSISTANT, 医学部, 助手 (10260845)
TSUTSUMI Kazuo  SAITAMA MEDICAL SCHOOL,ASSISTANT, 医学部, 助手 (70236917)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1993: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsNitric oxide / nitric oxide synthase / brain ischemia / nitro-L-arginine / brain edema / infarction
Research Abstract

The present study aimed at examining whether ischemic brain damage might develop mediated via a postischemic overproduction of nitric oxide in the brain tissue.
First, concentration of nitric oxide in the rat brain was directly measured, using newly devised microsensor. The exaggerated production (ca. 2-3 mumol) of nitric oxide was appeared in the affected hemisphere 15-20 minutes after MCAo and then reversed to the baseline. Three hours after MCAo, nitric oxide was yielded again over the baseline. The preischemic administration of LNA (Nomega-nitro-L-arginine, 1mg/kg, It is already reported that this dose is effective for prevention of ischemic brain edema following MCAo in rats) inhibited both of the above phenomena and ischemic brain edema was significantly blocked. Second, from the chronological study of Ca2^+-dependent and -independent NOS activity of cerebral MVs obtained from the affected hemisphere of the MCAo rats, Ca2^+-dependent NOS was first activated 10 times more than its … More baseline value immediately after MCAo. At 4 hours after MCAo, Ca2^+-independent NOS (9 times of the baseline value, p<0.01 vs.control) was siginifcantly activated (p<0.01 vs.control). At 48,168 hr after MCAo, in place of Ca2^+-independent, Ca2^+-dependent NOS was activated again (3 times of the baseline value, p<0.01 vs.control).
Third, effects of LNA on brain water content subjected to MCAo was examined. it was elucidated that repeated intraperitoneal injection of 0.01 to 1mg/kg LNA found to be effective for prevention of increase in brain water content, 72 hours after MCAo.
The present study suggested that the ischemic brain is always subjected to high-concentrated nitric oxide, yielded from cerebral MVs and that adequate inhibition of both type of NOS in cerebral MVs by LNA might be beneficial for prevention of ischemic brain edema. The present study provided the first evidence that two distinct types of NOSs were activated and involved in the pathogenesis of ischemic brain damage and that a total inhibition of NOS is not required. Less

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] 松居徹: "虚血性脳細胞障害とNO" Dementia. 8. 168-174 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 松居徹: "脳虚血とNO" 神経研究の進歩. 38. 957-966 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 松居徹: "脳虚血とNO" バイオクリニカ. 9. 28-35 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 松居徹: "脳虚血とNO" 現代医療. 27. 111-116 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nagafuji. T.: "Inhibition of nitrie onide synthesis mitigates ucneuic brain edema" J. Neuro chenu'stry. 61. S142 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nagafuji. T.: "Teuporcl profiles of Ca/cal nudulin dependant and-independat NOS actiuity" acta Neurochirurgica. 60. 285-288 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 松居徹: "CVD grand round series vol.1" ニューロン社, 192 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 松居徹: "脳虚血の分子医学(臨床医のための実験医学シリーズ20)" 羊土社, 174 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nagafuji T,Matsui T,Sugiyama M,Koide T,Asano T: "Inhibition of nitric oxide synthesis mitigates ischemic brain edema and infarction in rats" J Neurochemistry. 61. S142- (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Matsui T: "NO and ischemic brain damage" Dementia. 8 (Japanese). 168-174 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nagafuji T,Sugiyama M,Matsui T: "Temporal profiles of Ca/calmodulin dependent and -independent nitric oxide synthase activity in the rat brain microvessels following cerebral ischemia" Acta Neurochirurgica. 60. 285-288 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Matsui T,Asano T,Kumura E,Yoshimine T,Hayakawa T: "Role of nitric oxide in the pathogenesis underlying ischemic brain injury" Progress in Neurological Research. 38 (Japanese). 957-966 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Matsui T,Asano T: "NO and ischemic brain damage" Bioclinica. 9 (Japanese). 28-35 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Matsui T: "NO and brain ischemia" Gendai Iryou. 27 (Japanese). 111-116 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nagafuji T,Matsui T: "Role of nitric oxide in brain ischemia" Experimental Medicine. (in press) (Japanese). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 松居 徹: "虚血性脳細胞障害とNO" Dementia. 8. 168-174 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 松居 徹: "脳虚血とNO" 神経研究の進歩. 38. 957-966 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 松居 徹: "脳虚血とNO" バイオクリニカ. 9. 28-35 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 松居 徹: "脳虚血とNO" 現代医療. 27. 111-116 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Nagafuji.T.: "Inhibition of nitrie oxide synthesis mitigates unchenic brain edema," J.Neurochemistry. 61. S142 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Nagafuji.T.: "Teuporel profiles of Ca/calnudulin dependent and independent NOS activity" Acta Neurochirurgica. 60. 285-288 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 松居 徹: "CVD grand round series vol.1" ニューロン社, 192 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 松居 徹: "脳虚血の分子医学(臨床医のための実験医学シリーズ20)" 羊士社, 174 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Matsui T.et al: "Effects of NO synthase inhibitor on Permanent and Temporal ischenua" J cerebral blcod flow and Metabolism. 13. S151 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 松居 徹 他1名: "Nitric oxideと虚血性脳細胞障害" 実験医学. 11. 2457-2462 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 松居 徹: "Nitric oxide合成系" 現代医療. 26. 186-191 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 松居 徹: "Nitric oxideと虚血性脳細胞障害" Dementia. 4. (1994)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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