Pathogenesis of Osmotic Blood-Brain Barrier Opening and It's Application for the Treatment of Malignant Brain Tumor
| Project/Area Number |
60480332
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Nihon University |
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Principal Investigator |
MIYAGAMI Mitsusuke Assistant Professor, Department of Neurological Surgery, school of Medicine, Nihon University, 医学部, 講師 (60059508)
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| 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
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| Project Period (FY) |
1985 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| 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)
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| Keywords | Blood Brain Barrier / malignant brain tumor / chemotherapy / mannitol Hyperosmotic agent / CT / vascular permeability / シスプラチン |
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| 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.
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Report
(1 results)
Research Products
(14 results)
