Effects of adrenal cortical steroids and osmotic blood-brain barrier opening on methotrexate delivery to gliomas in the rodent

The factor of the blood-brain barrier

Edward Neuwelt, P. A. Barnett, D. D. Bigner, E. P. Frenkel

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

The effect of adrenal cortical steroids and osmotic blood-brain barrier modification on methotrexate delivery to normal and glioma-bearing rats was studied. In animals with the avian sarcoma virus-induced glioma, osmotic blood-brain barrier modification resulted in significantly increased delivery of methotrexate to the tumor-bearing hemisphere (including the tumor, the brain around the tumor, and the brain distant to the tumor), compared to the nonmodified hemisphere or to control animals. The administration of adrenal steroids, followed by intracarotid methotrexate, resulted in slightly decreased chemotherapeutic agent (methotrexate) delivery to the tumor, the brain around the tumor, and the brain distant to the tumor. When adrenal steroids were given prior to barrier modification and methotrexate therapy, the level of methotrexate was significantly less in the tumor. These studies provide evidence that the blood-brain barrier exists in tumors and is a factor in drug delivery to tumors. Steroid administration greatly interferes with the enhancement of drug delivery to tumors that can be achieved with osmotic blood-brain barrier modification.

Original languageEnglish (US)
Pages (from-to)4420-4423
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume79
Issue number14 I
StatePublished - 1982

Fingerprint

Blood-Brain Barrier
Methotrexate
Glioma
Rodentia
Steroids
Brain Neoplasms
Neoplasms
Avian Sarcoma Viruses
Pharmaceutical Preparations

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

@article{5fb4cd5b133f4cd999d8355aeb59b41b,
title = "Effects of adrenal cortical steroids and osmotic blood-brain barrier opening on methotrexate delivery to gliomas in the rodent: The factor of the blood-brain barrier",
abstract = "The effect of adrenal cortical steroids and osmotic blood-brain barrier modification on methotrexate delivery to normal and glioma-bearing rats was studied. In animals with the avian sarcoma virus-induced glioma, osmotic blood-brain barrier modification resulted in significantly increased delivery of methotrexate to the tumor-bearing hemisphere (including the tumor, the brain around the tumor, and the brain distant to the tumor), compared to the nonmodified hemisphere or to control animals. The administration of adrenal steroids, followed by intracarotid methotrexate, resulted in slightly decreased chemotherapeutic agent (methotrexate) delivery to the tumor, the brain around the tumor, and the brain distant to the tumor. When adrenal steroids were given prior to barrier modification and methotrexate therapy, the level of methotrexate was significantly less in the tumor. These studies provide evidence that the blood-brain barrier exists in tumors and is a factor in drug delivery to tumors. Steroid administration greatly interferes with the enhancement of drug delivery to tumors that can be achieved with osmotic blood-brain barrier modification.",
author = "Edward Neuwelt and Barnett, {P. A.} and Bigner, {D. D.} and Frenkel, {E. P.}",
year = "1982",
language = "English (US)",
volume = "79",
pages = "4420--4423",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "14 I",

}

TY - JOUR

T1 - Effects of adrenal cortical steroids and osmotic blood-brain barrier opening on methotrexate delivery to gliomas in the rodent

T2 - The factor of the blood-brain barrier

AU - Neuwelt, Edward

AU - Barnett, P. A.

AU - Bigner, D. D.

AU - Frenkel, E. P.

PY - 1982

Y1 - 1982

N2 - The effect of adrenal cortical steroids and osmotic blood-brain barrier modification on methotrexate delivery to normal and glioma-bearing rats was studied. In animals with the avian sarcoma virus-induced glioma, osmotic blood-brain barrier modification resulted in significantly increased delivery of methotrexate to the tumor-bearing hemisphere (including the tumor, the brain around the tumor, and the brain distant to the tumor), compared to the nonmodified hemisphere or to control animals. The administration of adrenal steroids, followed by intracarotid methotrexate, resulted in slightly decreased chemotherapeutic agent (methotrexate) delivery to the tumor, the brain around the tumor, and the brain distant to the tumor. When adrenal steroids were given prior to barrier modification and methotrexate therapy, the level of methotrexate was significantly less in the tumor. These studies provide evidence that the blood-brain barrier exists in tumors and is a factor in drug delivery to tumors. Steroid administration greatly interferes with the enhancement of drug delivery to tumors that can be achieved with osmotic blood-brain barrier modification.

AB - The effect of adrenal cortical steroids and osmotic blood-brain barrier modification on methotrexate delivery to normal and glioma-bearing rats was studied. In animals with the avian sarcoma virus-induced glioma, osmotic blood-brain barrier modification resulted in significantly increased delivery of methotrexate to the tumor-bearing hemisphere (including the tumor, the brain around the tumor, and the brain distant to the tumor), compared to the nonmodified hemisphere or to control animals. The administration of adrenal steroids, followed by intracarotid methotrexate, resulted in slightly decreased chemotherapeutic agent (methotrexate) delivery to the tumor, the brain around the tumor, and the brain distant to the tumor. When adrenal steroids were given prior to barrier modification and methotrexate therapy, the level of methotrexate was significantly less in the tumor. These studies provide evidence that the blood-brain barrier exists in tumors and is a factor in drug delivery to tumors. Steroid administration greatly interferes with the enhancement of drug delivery to tumors that can be achieved with osmotic blood-brain barrier modification.

UR - http://www.scopus.com/inward/record.url?scp=0020327951&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0020327951&partnerID=8YFLogxK

M3 - Article

VL - 79

SP - 4420

EP - 4423

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 14 I

ER -