Skip to main content
SpringerLink
Log in
Book cover

The Blood-Brain Barrier pp 133–144Cite as

Blood-Brain Barrier Permeability Using Tracers and Immunohistochemistry

  • Protocol

Part of the book series: Methods in Molecular Medicine™ ((MIMM,volume 89))

Abstract

The first report of blood-brain barrier (BBB) permeability by Paul Ehrlich (1) involved the use of the exogenous tracer Coerulean-S as described in Chapter 6. Over the years, tracers of different sizes were introduced to study the permeability properties of normal cerebral vessels in physiologic and pathologic states (Table 1). Tracers provide information about the permeability status of vessels immediately before sacrifice. The disadvantage of exogenous tracers is that there are side effects associated with the administration of some tracers in live animals. The properties and methods by which some of these tracers are used to study BBB permeability to proteins and ions in pathologic states will be described.

Table 1 The Exogenous Tracers Used to Detect Blood-Brain Barrier Permeability and the Methods to Detect Endogenous Protein Extravasations
Full size table

This is a preview of subscription content, log in via an institution.

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Ehrlich, P. (1885) Das Sauerstoff-Bedürfnis des Organismus: Eine farbenanalytiche Studie. Hirschwald, Berlin, 8, p. 167.

    Google Scholar 

  2. Nag, S. (1996) Immunohistochemical localization of extracellular matrix proteins in cerebral vessels in chronic hypertension. J. Neuropathol. Exp. Neurol. 55, 381–388.

    Article  PubMed  CAS  Google Scholar 

  3. Nag, S. (1996) Cold injury of the cerebral cortex: immunolocalization of cellular proteins and blood-brain barrier permeability studies. J. Neuropathol. Exp. Neurol. 55, 880–888.

    PubMed  CAS  Google Scholar 

  4. Dallasta, L. M., Pisarov, L. A., Esplen, J. E., et al. (1999) Blood-brain barrier tight junction disruption in human immunodeficiency virus-1 encephalitis. Amer. J. Pathol. 155, 1915–1927.

    Article  CAS  Google Scholar 

  5. Plumb, J., McQuaid, S., Mirakhur, M., and Kirk, J. (2002) Abnormal endothelial tight junctions in active lesions and normal-appearing white matter in multiple sclerosis. Brain Pathol. 12, 154–169.

    Article  PubMed  Google Scholar 

  6. Nag, S., Eskandarian, M. R., Davis, J., and Stewart, D. J. (2002) Differential expression of vascular endothelial growth factor A and B after brain injury. J. Neuropathol. Exp. Neurol. 61, 778–788.

    PubMed  CAS  Google Scholar 

  7. Goldmann, E. E. (1913) Vitalfarbung am Zentralnervensystem. G. Reimer, Berlin.

    Google Scholar 

  8. Tschirgi, R. D. (1950) Protein complexes and the impermeability of the blood-brain barrier to dyes. Am. J. Physiol. 163, 756.

    Google Scholar 

  9. Wolman, M., Klatzo, I., Chui, E., et al. (1981) Evaluation of the dye-protein tracers in pathophysiology of the blood-brain barrier. Acta Neuropathol. (Berl.) 54, 55–61.

    Article  CAS  Google Scholar 

  10. Nag, S. (1991) Protective effect of flunarizine on blood-brain barrier permeability alterations in acutely hypertensive rats. Stroke 22, 1265–1269.

    PubMed  CAS  Google Scholar 

  11. Straus, W. (1957) Segregation of an intravenously injected protein by “droplets” of the cells of rat kidney. J. Biophys. Biochem. Cytol. 3, 1037–1040.

    Article  PubMed  CAS  Google Scholar 

  12. Graham, R. C. Jr., and Karnovsky, M. J. (1966) The early stages of absorption of injected horseradish peroxidase in the proximal tubules of mouse kidney: Ultrastructural cytochemistry by a new technique. J. Histochem. Cytochem. 14, 291–302.

    PubMed  CAS  Google Scholar 

  13. Reese, T. S., and Karnovsky, M. J. (1967) Fine structural localization of a blood-brain barrier to exogenous peroxidase. J Cell Biol. 34, 207–217.

    Article  PubMed  CAS  Google Scholar 

  14. Cotran, R. S., Karnovsky, M. J. and Goth, A. (1968) Resistance of Wistar/Furth rats to mast cell-damaging effect of horseradish peroxidase. J. Histochem. Cytochem. 16, 382–383.

    PubMed  CAS  Google Scholar 

  15. Deimann, W., Taugner, R., and Fahimi, H. D. (1976) Arterial hypotension induced by horseradish peroxidase in various rat strains. J. Histochem. Cytochem. 24, 1213–1217.

    PubMed  CAS  Google Scholar 

  16. Sjaastad, Ø. V., Blom, A. K., and Haye, R. (1984) Hypotensive effects in cats caused by horseradish peroxidase mediated by metabolites of arachidonic acid. J. Histochem. Cytochem. 32, 1328–1330.

    PubMed  CAS  Google Scholar 

  17. Nag, S., Robertson, D. M., and Dinsdale, H. B. (1979) Quantitative estimate of pinocytosis in experimental acute hypertension. Acta Neuropathol (Berl.) 46, 107–116.

    Article  CAS  Google Scholar 

  18. Westergaard E., and Brightman, M. W. (1973) Transport of proteins across normal cerebral arterioles. J. Comp. Neurol. 152, 17–44.

    Article  PubMed  CAS  Google Scholar 

  19. Nag, S. (1991) Effect of atrial natriuretic factor on permeability of the blood-cerebrospinal fluid barrier. Acta Neuropathol. (Berl.) 82, 82–274.

    Article  Google Scholar 

  20. Nag, S. (1995) Role of endothelial cytoskeleton in blood-brain barrier permeability to protein. Acta Neuropathol. (Berl.) 90, 454–460.

    Article  CAS  Google Scholar 

  21. Nag, S. (1998) Blood-brain barrier permeability measured with histochemistry. In Introduction to the Blood-Brain Barrier. Methodology, Biology and Pathology. Pardridge, W. M., ed. Cambridge University Press, Cambridge, UK, pp. 113–121.

    Chapter  Google Scholar 

  22. Stewart, P. A. (2000) Endothelial vesicles in the blood-brain barrier: are they related to permeability? Cell. Mol. Neurobiol. 20, 149–163.

    Article  PubMed  CAS  Google Scholar 

  23. Raymond, J. J., Robertson, D. M., Dinsdale, H. B., Nag, S. (1884) Pharmacological modification of blood-brain barrier permeability following a cold lesion. Can. J. Neurol. Sci. 11, 447–451.

    Google Scholar 

  24. Reese T. S., Feder N., and Brightman, M. W. (1971) Electron microscopic study of the blood-brain and blood-cerebrospinal fluid barriers with microperoxidase. J. Neuropathol. Exp. Neurol. 30, 137–138.

    PubMed  CAS  Google Scholar 

  25. Nag, S. (1988) Calcium-activated adenosine-triphosphatase in intracerebral arterioles in acute hypertension. Acta Neuropathol. (Berl.) 75, 547–553.

    Article  CAS  Google Scholar 

  26. Nag, S. (1990) Ultrastructural localization of Na+, K+-ATPase in cerebral endothelium in acute hypertension. Acta Neuropathol. (Berl.) 80, 7–11.

    Article  CAS  Google Scholar 

  27. Harik, S. I., McGunigal, T. Jr. (1984) The protective influence of the locus ceruleus on the blood-brain barrier. Ann. Neurol. 15, 568–574.

    Article  PubMed  CAS  Google Scholar 

  28. Dorovini-Zis, K., Sato, M., Goping, G., Rapoport, S., and Brightman, M. (1983) Ionic lanthanum passage across cerebral endothelium exposed to hyperosmotic arabinose. Acta Neuropathol. (Berl.) 60, 49–60.

    Article  CAS  Google Scholar 

  29. Nag, S., and Pang, S. C. (1989) Effect of atrial natriuretic factor on blood-brain barrier permeability. Can. J. Physiol. Pharmacol. 67, 637–640.

    PubMed  CAS  Google Scholar 

  30. Bouldin, T. W., and Krigman, M. R. (1975) Differential permeability of cerebral capillary and choroid plexus to lanthanum ions. Brain Res. 99, 444–448.

    Article  PubMed  CAS  Google Scholar 

  31. Castel, M., Sahar, A., and Erlij, D. (1974) The movement of lanthanum across diffusion barriers in the choroid plexus of the cat. Brain Res. 67, 178–184.

    Article  PubMed  CAS  Google Scholar 

  32. Bolton, S. J., Anthony, D. C., and Perry, V. H. (1998) Loss of the tight junction proteins occludin and zonula occludens-1 from cerebral vascular endothelium during neutrophil-induced blood-brain barrier breakdown in vivo. Neuroscience 86, 1245–1257.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Neuropathology, University of Toronto, Toronto, Canada

    Sukriti Nag

  2. Toronto Western Research Institute, University Health Network, Toronto, Canada

    Sukriti Nag

Authors
  1. Sukriti Nag
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Division of Neuropathology, University of Toronto, Toronto, Canada

    Sukriti Nag

  2. Toronto Western Research Institute and Department of Pathology, University Health Network, Toronto, Canada

    Sukriti Nag

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Humana Press Inc., Totowa, NJ

About this protocol

Cite this protocol

Nag, S. (2003). Blood-Brain Barrier Permeability Using Tracers and Immunohistochemistry. In: Nag, S. (eds) The Blood-Brain Barrier. Methods in Molecular Medicine™, vol 89. Humana Press. https://doi.org/10.1385/1-59259-419-0:133

Download citation

  • DOI: https://doi.org/10.1385/1-59259-419-0:133

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-073-1

  • Online ISBN: 978-1-59259-419-1

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation