Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1979 Aug;64(2):684–688. doi: 10.1172/JCI109509

Osmotic blood-brain barrier disruption. Computerized tomographic monitoring of chemotherapeutic agent delivery.

E A Neuwelt, K R Maravilla, E P Frenkel, S I Rapaport, S A Hill, P A Barnett
PMCID: PMC372166  PMID: 457877

Abstract

The present study describes a canine model of transient reversible blood-brain barrier disruption with hyperosmolar mannitol infusion into the internal carotid artery. Studies in this model show that osmotic blood-brain barrier disruption before intracarotid infusion of methotrexate results in markedly elevated (therapeutic) levels of drug in the ipsilateral cerebral hemisphere. Levels in the cerebrospinal fluid correlate poorly and inconsistently with brain levels. Computerized tomograms in this canine model provide a noninvasive monitor of the degree, time-course, and localization of osmotic blood-brain barrier disruption.

Full text

PDF
688

Images in this article

686Image
on p.686
686Image
on p.686
687Image
on p.687

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Benjamin R. S., Wiernik P. H., Bachur N. R. Adriamycin chemotherapy--efficacy, safety, and pharmacologic basis of an intermittent single high-dosage schedule. Cancer. 1974 Jan;33(1):19–27. doi: 10.1002/1097-0142(197401)33:1<19::aid-cncr2820330107>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
  2. Kimelberg H. K., Kung D., Watson R. E., Reiss F. L., Biddlecome S. M., Bourke R. S. Direct administration of methotrexate into the central nervous system of primates. Part 1: Distribution and degradation of methotrexate in nervous and systemic tissue after intraventricular injection. J Neurosurg. 1978 Jun;48(6):883–894. doi: 10.3171/jns.1978.48.6.0883. [DOI] [PubMed] [Google Scholar]
  3. Levin V. A., Clancy T. P., Ausman J. I., Rall D. P. Uptake and distribution of 3 H-methotrexate by the murine ependymoblastoma. J Natl Cancer Inst. 1972 Apr;48(4):875–883. [PubMed] [Google Scholar]
  4. Posner J. B. Management of central nervous system metastases. Semin Oncol. 1977 Mar;4(1):81–91. [PubMed] [Google Scholar]
  5. Rapoport S. I., Thompson H. K., Bidinger J. M. Equi-osmolal opening of the blood-brain barrier in the rabbit by different contrast media. Acta Radiol Diagn (Stockh) 1974 Jan;15(1):21–32. doi: 10.1177/028418517401500103. [DOI] [PubMed] [Google Scholar]
  6. Shapiro W. R., Young D. F., Mehta B. M. Methotrexate: distribution in cerebrospinal fluid after intravenous, ventricular and lumbar injections. N Engl J Med. 1975 Jul 24;293(4):161–166. doi: 10.1056/NEJM197507242930402. [DOI] [PubMed] [Google Scholar]
  7. Stoller R. G., Hande K. R., Jacobs S. A., Rosenberg S. A., Chabner B. A. Use of plasma pharmacokinetics to predict and prevent methotrexate toxicity. N Engl J Med. 1977 Sep 22;297(12):630–634. doi: 10.1056/NEJM197709222971203. [DOI] [PubMed] [Google Scholar]
  8. Tator C. H. Chemotherapy of brain tumors. Uptake of tritiated methotrexate by a transplantable intracerebral ependymoblastoma in mice. J Neurosurg. 1972 Jul;37(1):1–8. doi: 10.3171/jns.1972.37.1.0001. [DOI] [PubMed] [Google Scholar]
  9. Vick N. A., Khandekar J. D., Bigner D. D. Chemotherapy of brain tumors. Arch Neurol. 1977 Sep;34(9):523–526. doi: 10.1001/archneur.1977.00500210025002. [DOI] [PubMed] [Google Scholar]
  10. Wang Y., Lantin E., Sutow W. W. Methotrexate in blood, urine, and cerebrospinal fluid of children receiving high doses by infusion. Clin Chem. 1976 Jul;22(7):1053–1056. [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES