Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1995 Oct 1;182(4):1037–1043. doi: 10.1084/jem.182.4.1037

Penetration of the blood-brain barrier: enhancement of drug delivery and imaging by bacterial glycopeptides

PMCID: PMC2192296  PMID: 7561677

Abstract

The blood-brain barrier restricts the passage of many pharmacological agents into the brain parenchyma. Bacterial glycopeptides induce enhanced blood-brain barrier permeability when they are present in the subarachnoid space during meningitis. By presenting such glycopeptides intravenously, blood-brain barrier permeability in rabbits was enhanced in a reversible time- and dose-dependent manner to agents < or = 20 kD in size. Therapeutic application of this bioactivity was evident as enhanced penetration of the antibiotic penicillin and the magnetic resonance imaging contrast agent gadolinium-diethylene-triamine- pentaacetic acid into the brain parenchyma.

Full Text

The Full Text of this article is available as a PDF (1.5 MB).

Selected References

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

  1. Banks W. A., Audus K. L., Davis T. P. Permeability of the blood-brain barrier to peptides: an approach to the development of therapeutically useful analogs. Peptides. 1992 Nov-Dec;13(6):1289–1294. doi: 10.1016/0196-9781(92)90037-4. [DOI] [PubMed] [Google Scholar]
  2. Burroughs M., Rozdzinski E., Geelen S., Tuomanen E. A structure-activity relationship for induction of meningeal inflammation by muramyl peptides. J Clin Invest. 1993 Jul;92(1):297–302. doi: 10.1172/JCI116565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Friden P. M., Walus L. R., Musso G. F., Taylor M. A., Malfroy B., Starzyk R. M. Anti-transferrin receptor antibody and antibody-drug conjugates cross the blood-brain barrier. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4771–4775. doi: 10.1073/pnas.88.11.4771. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Friden P. M., Walus L. R., Watson P., Doctrow S. R., Kozarich J. W., Bäckman C., Bergman H., Hoffer B., Bloom F., Granholm A. C. Blood-brain barrier penetration and in vivo activity of an NGF conjugate. Science. 1993 Jan 15;259(5093):373–377. doi: 10.1126/science.8420006. [DOI] [PubMed] [Google Scholar]
  5. Goldman W. E., Klapper D. G., Baseman J. B. Detection, isolation, and analysis of a released Bordetella pertussis product toxic to cultured tracheal cells. Infect Immun. 1982 May;36(2):782–794. doi: 10.1128/iai.36.2.782-794.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Inamura T., Nomura T., Bartus R. T., Black K. L. Intracarotid infusion of RMP-7, a bradykinin analog: a method for selective drug delivery to brain tumors. J Neurosurg. 1994 Nov;81(5):752–758. doi: 10.3171/jns.1994.81.5.0752. [DOI] [PubMed] [Google Scholar]
  7. Kadurugamuwa J. L., Hengstler B., Zak O. Cerebrospinal fluid protein profile in experimental pneumococcal meningitis and its alteration by ampicillin and anti-inflammatory agents. J Infect Dis. 1989 Jan;159(1):26–34. doi: 10.1093/infdis/159.1.26. [DOI] [PubMed] [Google Scholar]
  8. Krueger J. M., Davenne D., Walter J., Shoham S., Kubillus S. L., Rosenthal R. S., Martin S. A., Biemann K. Bacterial peptidoglycans as modulators of sleep. II. Effects of muramyl peptides on the structure of rabbit sleep. Brain Res. 1987 Feb 17;403(2):258–266. doi: 10.1016/0006-8993(87)90063-1. [DOI] [PubMed] [Google Scholar]
  9. Quagliarello V., Scheld W. M. Bacterial meningitis: pathogenesis, pathophysiology, and progress. N Engl J Med. 1992 Sep 17;327(12):864–872. doi: 10.1056/NEJM199209173271208. [DOI] [PubMed] [Google Scholar]
  10. Tuomanen E. I., Prasad S. M., George J. S., Hoepelman A. I., Ibsen P., Heron I., Starzyk R. M. Reversible opening of the blood-brain barrier by anti-bacterial antibodies. Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7824–7828. doi: 10.1073/pnas.90.16.7824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Tuomanen E., Liu H., Hengstler B., Zak O., Tomasz A. The induction of meningeal inflammation by components of the pneumococcal cell wall. J Infect Dis. 1985 May;151(5):859–868. doi: 10.1093/infdis/151.5.859. [DOI] [PubMed] [Google Scholar]
  12. Wispelwey B., Lesse A. J., Hansen E. J., Scheld W. M. Haemophilus influenzae lipopolysaccharide-induced blood brain barrier permeability during experimental meningitis in the rat. J Clin Invest. 1988 Oct;82(4):1339–1346. doi: 10.1172/JCI113736. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES