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GENE THERAPY FOR CEREBRAL VASOSPASM ASSOCIATED WITH SUBARACHNOID HEMORRHAGE

Research Project

Project/Area Number 08457367
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionOKAYAMA UNIVERSITY

Principal Investigator

ASARI Shoji  OKAYAMA UNIVERSITY,MEDICAL SCHOOL,PROFESSOR, 医学部, 教授 (40175857)

Co-Investigator(Kenkyū-buntansha) NINOMIYA Yoshifumi  OKAYAMA UNIVERSITY MEDICAL SCHOOL,ROFESSOR, 医学部, 教授 (70126241)
TOMITA Susumu  OKAYAMA UNIVERSITY MEDICAL SCHOOL,ASSISTANT ROFESSOR, 医学部, 助手 (90237115)
DATE Isao  OKAYAMA UNIVERSITY UNIVERSITY MEDICAL SCHOOL,HOSPITAL,ASSISTANT ROFESSOR, 医学部附属病院, 助手 (70236785)
MATSUMOTO Kengo  OKAYAMA UNIVERSITY MEDICAL SCHOOL,ASSOCIATE PROFESSOR, 医学部, 助教授 (10190521)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥7,900,000 (Direct Cost: ¥7,900,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1997: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1996: ¥5,300,000 (Direct Cost: ¥5,300,000)
KeywordsCEREBRAL VASOSPASM / SUBARACHNOID HEMORRHAGE / GENE THERAPY / リポリーム / アデノウィルス / 血管平滑筋 / 血管内皮細胞 / 遺伝子導入 / リポソーム / アデノウイルス / クモ膜下出血 / エンドセリン / 転写因子
Research Abstract

We have investigated the pathophysiology of cerebral vasospasm associated with subarachnoid hemorrhage using molecular biology techniques, that is, in vivo study using animal models of subarachnoid hemorrhage, We have shown that cistemal administration of antisenseoligonucleotide for entothelin could releave the early stage of cerebral vasospasm, administration of antisenseoligonucleotide for collagen reduced the degree of cerebral vasospasm and cisternal administration of antisenseoligonucleotide for endothelin-liposome complex suppressed cerebral vasospasm, We have also shown that decoy-liposome complex administration of NF-kB could improve the degree of vasospasm, suggesting that inflamation plays an important role in cerebral vasospasm.
We evaluated vectors for gene delivery. In vitro study showed that adenoviral vector with Lac Z gene could be transfected by cultured endothelial cells and smooth muscle cells exposed to hemolysate. In vivo study also showed that adenoviral vector could induce be used for gene transfection to cerebral vessels.
The relationship between the cerebral vasospasm and aging was also investigated. The response of cerebral vessels to papaverin chloride was
decreased with aging.

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Shigeki Ono. et al.: "Decoy Administration of NF-kB into the Subarachnoid Space for cerebral Angio pathy" HUMAN GENE THERAPY. 9. 1003-1011 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shigeki Ono. et al.: "Three-Dimensional Analysis of Vasospastic Major Cerebral Arteries in Rats with the Corrosion Cast Technique" Stroke. 28. 1631-1638 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Keisuke Onoda, et al: "Role of extracellular matrix in experimental vasospasm-Inhibitory effect of antisense oligonucleotide on collagen induction" Stroke. 27. 2102-2109 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Keisuke Onoda, et al: "Inhibition of vascular contraction by intracicternal administraction of preproendothelin - Im RNA antisense oligo DNA in a rat experimental vasospasm model" Journal of Neurosurgery. 85. 846-852 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ono S,I.Date, Onoda K,Shiota T,Asari S,Ohmoto T,Ninomiya Y,Morishita R: "Decoy Administration of NF-kB into the Subarachnoid space for Cerebral Angiopathy" HUMAN GENE THERAPY. 9. 1003-1011 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ono S,Date I,Nakajima M,Onoda K,Ogihara K,Shiota T,Asari S,Ohmoto T,Ninomiya Y,Yabuno N: "Three dimensional analysis of vasospastic major cerebral arteries in rats using corrosion cast technique" Stroke. 28. 1631-1638 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Onoda K,Ono S,Ogihara K,Shiota T,Asari S,Ohmoto T,Ninomiya Y: "Role of extracellular matrix in experimental vasospasm-Inhibitory effect of antisense oligonucleotide on collagen induction-" Stroke. 27. 2102-2109 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Onoda K,Ono S,Ogihara K,Shiota T,Asari S,Ohmoto T,Ninomiya Y: "Inhibition of vascular contraction by intracicternal administration of preproendothelin-1 mRNA antisense oligoDNA in a rat experimental vasospasm model" J Neurosurg. 85. 846-852 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 中島正明: "脳血管攣縮における加齢の影響-塩酸パパベリンに対する反応性の相違による検討-" 脳血管攣縮. 13. 226-230 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 小野成紀: "脳脊髄液を介したNf-κβおとり核酸による脳血管攣縮の遺伝子治療" 脳血管攣縮. 13. 251-256 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Keisuke Onoda: "Inhibition of vascular contraction by intracisternal administration of preproendothelin-1 mRNA antisense oligo DNA in rat experimental vasospsm model" Journal of Neurosurgery. 85. 846-852 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 小野田恵介: "Inhibition of vascular contraction by intracisternal administration of preproendothelin-1 mRNA antisense oligoDNA in a rat experimental vasospasm model" Journal of Neurosurgery. 85. 846-852 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 小野田恵介: "Role of extracellular matrix in experimental rasospasm ; Inhibitory effect of antisense digonucleotide on collagen induction" Stroke. 27. 2102-2109 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 小野成紀: "ラットくも膜下出血後の攣縮脳底動脈における転写因子発現の経時的変化について" Proc.Spasm.Symp.Vol.12. (in press).

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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