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Pathogenesis of Osmotic Blood-Brain Barrier Opening and It's Application for the Treatment of Malignant Brain Tumor

Research Project

Project/Area Number 60480332
Research Category

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

Allocation TypeSingle-year Grants
Research Field Cerebral neurosurgery
Research InstitutionNihon University

Principal Investigator

MIYAGAMI Mitsusuke  Assistant Professor, Department of Neurological Surgery, school of Medicine, Nihon University, 医学部, 講師 (60059508)

Co-Investigator(Kenkyū-buntansha) TSUBOKAWA Takashi  Professor, Department of Neurological Surgery, school of Medicine, Nihon Univers, 医学部, 教授 (80058958)
HAYASHI Nariyuki  Assistant Professor, Department of Neurological Surgery, school of Medicine, Nih, 医学部, 講師 (10059503)
田副 誠  日本大学, 医学部, 助手
KAGAWA Yukihide  Department of Neurological Surgery, School of Medicine, Nihon University, 医学部, 助手 (60150728)
TAZOE Makoto  Department of Neurological Surgery, School of Medicine, school of Medicine, Niho
Project Period (FY) 1985 – 1986
Project Status Completed (Fiscal Year 1986)
Budget Amount *help
¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 1986: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1985: ¥5,200,000 (Direct Cost: ¥5,200,000)
KeywordsBlood Brain Barrier / malignant brain tumor / chemotherapy / mannitol Hyperosmotic agent / CT / vascular permeability / シスプラチン
Research Abstract

It has been suggested that blood brain barrier opened trasiently by infusion of hyper-osmotic agent through internal carotid artery. The vascular extravasation was more investigated with evans blue and horseradish peroxidase(HRP) as tracers in relation with the concerntration of hyperosmotic agents. It has been shown by using ultracytochemical method that <Na^+> - <K^+> - ATPase activity in the endothlial cell membranes of blood vesels and glia cell membranes was not lowered and kept functionaly at 30 minutes after intracarotid infusion of hyperosmotic agents.
The concentrations of ACNU in both the tumor tissues of 12 astrocytomas and blood were measured following intracarotid administration of ACNU (100mg), in relation to alteration of enhanced CT under reversible transient osmotic blood-brain barrier disruption using 20% mannitol. The ACNU levels in the solid part of malignant astocytoma were 4-8 times higher than those in the blood. However, ACNU in the necrotic area, cytic fluid in the tumor or normal brain tissue around the tumor was not increased to more than the levels in the blood.
Also It has been suggested from our results with 14 experimental brain tumors (gL gliosarcoma) that intracarotid infusion of 20% mannitol should be employed as a hyperosmotic agent for blood-brain barrier disruption in order to increase drug delivery to malignant brain tumors since the drug penetration to the normal brain was less with 20% mannitol than with 25% mannitol.
The results of treatment for the malignant astrocytoma were compared in intracarotid infusion of ACNU with 20% mannitol with the intracarotid infusion of simple ACNU without hyperosmotic agent. 5 cases of 10 rest tumors after operation decreased to 50% in tumor size on CT (complete disappearance in 2 of 5 cases) on the group with combined thrapy of intracarotid infusion of ACNU with 20% mannitol without permanent complications depending on its procedure. Prognostic infusion of 20% mannitol than in those without it.

Report

(1 results)
  • 1986 Final Research Report Summary
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] 宮上光祐 他: 脳神経外科. 13. 955-983 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] 宮下光祐 他: CT研究. 7. 411-418 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] 宮上光祐 他: 新薬と臨床. 34. 1935-1943 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] 賀川幸英 他: J.Clin.Electron Microscopy. 18. 5-6 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] 宮上光祐 他: 臨床放射線. 31. 15-21 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] 宮上光祐 他: J.Neurooncology.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] 坪川孝志 他: J.Neurooncology.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Mitsusuke Miyagami: "ACNU delivery to malignant glioma tissue by osmotic blood brain barrier modification with intracarotid infusion of hyperosmoral mannitol" Neurological surgery(Japan). 13. 955-983 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Mitsusuke Miyagami: "Contrast-enhancement CT with osmotic blood brain barrier modification of brain tumors" Progress in computerized tomography. 7. 411-418 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Mitsusuke Miyagami: "J. New Remedies and clinics" The effect of glycerol for the antibiotic(cefotaxime) delivery to cerebrospinal fluid. 34. 1935-1943 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Mitsusuke Miyagami: "Mannitol contrast enhancement CT" Jpn. J. Clin. Radiol.31. 15-21 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Mitsusuke Miyagami: "Cis-diammindichloro-platinum delivery to gL gliosarcom tumors and normal brain in Fischer 344 rats following osmotic blood-brain barrier disruption." J. Neurooncology. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Takashi Tsubokawa: "Relationship between water-soluble anti-tumor nitrosourea(ACNU) delivery to glioma tissue and enhancement CT density following osmotic blood-brain barrier distruption." J. Neurooncology.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Yukihide Kagawa: "Opening of the blood-brain barrier by use of hyperosmolar solution: Ultracytochemical localization <NA^+> - <K^+> -ATPase and peroxidase" J. Clin. Electron Microscopy. 18. 5-6 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary

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Published: 1987-03-31   Modified: 2016-04-21  

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