Skip to main content

Advertisement

SpringerLink
Log in

In Vitro Methods in the Study of Viral and Prion Permeability Across the Blood–Brain Barrier

  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Summary

1. Infectious agents capable of entering the central nervous system (CNS) produce some of the most dreaded diseases known to man. The infectious agent within the CNS is often protected by the blood–brain barrier (BBB), shielded from endogenous and exogenous anti-infectious agents.

2. The use of in vitro methods offers many advantages to the study of how infectious agents interact with the BBB. Two such agents which negotiate the BBB early in the course of disease before damage to the BBB are the autoimmune deficiency syndrome virus, or human immunodeficiency virus 1, and scrapie prion. Our laboratories have used in vitro methods to study these agents.

3. Here, we review some of the results form our laboratories and those of others.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Abbott, N. J. (2002). Astrocyte-endothelial interactions and blood–brain barrier. J. Anatomy 200:629–638.

    Article  CAS  Google Scholar 

  • Audus, K. L., and Borchardt, R. T. (1987). Bovine brain microvessel endothelial cell monolayers as a model system for the blood–brain barrier. Biological Approaches to the Controlled Delivery of Drugs, Ann. NY Acad. Sci., pp. 9–18, New York.

    Google Scholar 

  • Bagasra, O., Lavi, E., Bobroski, L., Khalili, K., Pestaner, J. P., Tawadros, R., and Pomerantz, R. J. (1996). Cellular reservoirs of HIV-1 in the central nervous system of infected individuals: Identification by the combination of in situ polymerase chain reaction and immunohistochemistry. AIDS 10:573–585.

    Article  PubMed  CAS  Google Scholar 

  • Banks, W. A., Akerstrom, V., and Kastin, A. J. (1998). Adsorptive endocytosis mediates the passage of HIV-1 across the blood–brain barrier: Evidence for a post-internalization coreceptor. J. Cell Sci. 111:533–540.

    PubMed  CAS  Google Scholar 

  • Banks, W. A., Freed, E. O., Wolf, K. M., Robinson, S. M., Franko, M., and Kumar, V. B. (2001). Transport of human immunodeficiency virus type 1 pseudoviruses across the blood–brain barrier: Role of envelope proteins and adsorptive endocytosis. J. Virol. 75:4681–4691.

    Article  PubMed  CAS  Google Scholar 

  • Banks, W. A., Kastin, A. J., and Akerstrom, V. (1997). HIV-1 protein gp120 crosses the blood–brain barrier: Role of adsorptive endocytosis. Life Sci. 61:L119–L125.

    Article  Google Scholar 

  • Britton, T. C., Al-Sarraj, S., Shaw, C., Campbell, T., and Collinge, J. (1995). Sporadic Creutzfeldt-Jakob disease in a 16-year-old in the UK. Lancet 3469:1155.

    Article  Google Scholar 

  • Brown, D. R. (2002). Mayhem of the multiple mechanisms: Modeling neurodegeneration in prion disease. J. Neurochem. 82:209–215

    Article  PubMed  CAS  Google Scholar 

  • Caughy, B., and Raymond, G. J. (1993). Sulfated polyanion inhibition of scrapie-associated PrP accumulation in cultured cells. J. Virol. 67:643–650.

    Google Scholar 

  • Chou, S., and Dix, R. D. (1989). Viral infections and the blood–brain barrier. In Neuwelt, E. A. (ed.) Implications of the Blood–Brain Barrier and Its Manipulation, Vol. 2, Clinical Aspects, Plenum Publishing Corporation, New York, pp. 449–468.

    Google Scholar 

  • Deli, M. A., and Joo, F. (1996). Culture vascular endothelial cells of the brain. Keio J. Med. 45:183–198.

    PubMed  CAS  Google Scholar 

  • Deli, M. A., Niwa, M., Katamine, S., and Abraham, C. S. (1999). Pentosan in transmissible spongiform encephalopathies. Lancet 353:1272.

    Article  PubMed  CAS  Google Scholar 

  • Deli, M. A., Sakaguchi, S., Nakaoke, R., Abraham, C. S., Takahata, H., Kopacek, J., Shigematsu, K., Katamine, S., and Niwa, M. (2000). PrP fragment 106–126 is toxic to cerebral endothelial cells expressing PrP(C). Neuroreport 11:3931–3936.

    Article  PubMed  CAS  Google Scholar 

  • Di Stefano, M., Gray, F., Leitner, T., and Chiodi, F. (1996). Analysis of ENV V3 sequences from HIV-1-infected brain indicates restrained virus expression throughout the disease. J. Med. Virol. 49:41–48.

    Article  PubMed  CAS  Google Scholar 

  • Dubin, N. H., Strandberg, J. D., Craft, C. F., Parmley, T. H., Blake, D. A., and King, T. M. (1982). Effect of intrauterine and intravascular quinacrine administration on histopathology, blood chemistry, and hematology in cynomolgus monkeys. Fertil. Steril. 38:735–740.

    PubMed  CAS  Google Scholar 

  • Edinger, A. L., Mankowski, J. L., Doranz, B. J., Margulies, B. J., Lee, B., Rucker, J., Sharron, M., Hoffman, T. L., Berson, J. F., Zink, M. C., Hirsch, V. M., Clements, J. E., and Doms, R. W. (1997). CD4-independent, CCR5-dependent infection of brain capillary endothelial cells by a neurovirulent simian immunodeficiency virus strain. Proc. Natl Acad. Sci. USA 94:14742–14747.

    Article  PubMed  CAS  Google Scholar 

  • Falangola, M. F., Hanly, A., Galvao-Castro, B., and Petito, C. K. (1995). HIV infection of human choroid plexus: A possible mechanism of viral entry into the CNS. J. Neuropathol. Exp. Neurol. 54:497–503.

    Article  PubMed  CAS  Google Scholar 

  • Farquhar, C., Dickinson, A., and Bruce, M. (1999). Prophylactic potential of pentosan polysulphate in transmissible spongiform encephalopathies. Lancet 353:117.

    Article  PubMed  CAS  Google Scholar 

  • Feng, Y., Broder, C. C., Kennedy, P. E., and Berger, E. A. (1996). HIV-1 entry cofactor: Function cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 272:872–877.

    Article  PubMed  CAS  Google Scholar 

  • Filice, G., Cereda, P. M., and Varnier, O. E. (1988). Infection in rabbits with human immunodeficiency virus. Nature 335:366–369.

    Article  PubMed  CAS  Google Scholar 

  • Forloni, G., Angeretti, N., Chiesa, R., Monzani, E., Salmona, M., Bugiani, O., and Tagliavini, F. (1993). Neurotoxicity of a prion protein fragment. Nature 362:543–546.

    Article  PubMed  CAS  Google Scholar 

  • Furukawa, H., Takahashi, M., Nakajima, M., and Yamada, T. (2002). Prospects of the therapeutic approaches to Creutzfeldt-Jakob disease: A clinical trial of antimalarial, quinacrine. Nippon Rinsho 60:1649–1657.

    PubMed  Google Scholar 

  • Gilat, D., Hershkoviz, R., Mekori, Y. A., Vlodavsky, I., and Lider, O. (1994). Regulation of adhesion of CD4+ T lymphocytes to intact or heparinase-treated subendothelial extracellular matrix by diffusible or anchored RANTES and MIP-1 beta. J. Immunol. 153:4899–4906.

    PubMed  CAS  Google Scholar 

  • Grossman, D. M., Banks, W. A., LeBlanc, J., and Dejace, P. (1998). Prevalence of hypernatremia in HIV-infected VA patients. J. Invest. Med. 46:46A.

    Google Scholar 

  • Gu, Y., Fujioka, H., Mishra, R. S., Li, R., and Singh, N. (2002). Prion peptide 106–126 modulates the aggregation of cellular prion protein and induces the synthesis of potentially neurotoxic transmembrane PrP. J. Biol. Chem. 277:2275–2286.

    Article  PubMed  CAS  Google Scholar 

  • Hardebo, J. E., and Kahrstrom, J. (1985). Endothelial negative surface charge areas and blood–brain barrier function. Acta Physiol. Scand. 125:495–499.

    Article  PubMed  CAS  Google Scholar 

  • Hernandez, L. D., Hoffman, L. R., Wolfsber, T. G., and White, J. M. (1996). Virus–cell and cell–cell fusion. Annu. Rev. Dev. Biol. 12:627–661.

    Article  CAS  Google Scholar 

  • Hill, J. M., Mervis, R. F., Avidor, R., Moody, T. W., and Brenneman, D. E. (1993). HIV envelope protein-induced neuronal damage and retardation of behavioral development in rat neonates. Brain Res. 603:222–233.

    Article  PubMed  CAS  Google Scholar 

  • Hosmalin, A., Clerici, M., Houghten, R., Pendleton, C. D., Flexner, C., Lucey, D. R., Moss. B., Germain, R. N., Shearer, G. M., and Berzofsky, J. A. (1990). An epitope in human immunodeficiency virus 1 reverse transcriptase recognized by both mouse and human cytotoxic T lymphocytes. Proc. Natl Acad. Sci. USA 87:2344–2348.

    Article  PubMed  CAS  Google Scholar 

  • Hunter, N., Foster, J., Chong, A., McCutcheon, S., Parnham, D., Eaton, S., MacKenzie, C., and Houston, F. (2002). Transmission of prion disease by blood transfusion. J. Gen. Virol. 83:2897–2905.

    PubMed  CAS  Google Scholar 

  • Hurwitz, A. A., Berman, J. W., and Lyman, W. D. (1994). The role of the blood–brain barrier in HIV infection of the central nervous system. Adv. Neuroimmunol. 4:249–256.

    Article  PubMed  CAS  Google Scholar 

  • Joo, F. (1992). The cerebral microvessels in culture, an update. J. Neurochem. 58:1–17.

    Article  PubMed  CAS  Google Scholar 

  • Kalomiris, E. L., and Bourguignon, L. Y. (1988). Mouse T lymphoma cells contain a transmembrane glycoprotein (GP85) that binds ankyrin. J. Cell Biol. 106:319–327.

    Article  PubMed  CAS  Google Scholar 

  • Kopacek, J., Sakaguchi, S., Shigematsu, K., Nishida, N., Atarashi, R., Nakaoke, R., Moriuchi, R., Niwa, M., and Katamine, S. (2000). Upregulation of the genes encoding lysosomal hydrolases, a perforin-like protein, and peroxidases in the brains of mice affected with an experimental prion disease. J. Virol. 74:411–417.

    Article  PubMed  CAS  Google Scholar 

  • Koperk, O., Kovacs, G. G., Ritchie, D., Ironside, J. W., Budka, H., and Wick, G. (2002). Disease-associated prion protein in vessel walls. Am. J. Pathol. 161:1979–1984.

    Google Scholar 

  • Koyanagi, Y., Tanaka, Y., Kira, J., Ito, M., Hioki, K., Misawa, N., Kawano, Y., Yamasaki, K., Tanaka, R., Suzuki, Y., Ueyama, Y., Terada, E., Tanaka, T., Myasaka, M., Kobayashi, T., Kumazawa, Y., and Yamamoto, N. (1997). Primary human immunodeficiency virus type 1 viremia and central nervous system invasion in a novel hu-PBL-immunodeficient mouse strain. J. Virol. 71:2417–2424.

    PubMed  CAS  Google Scholar 

  • Lafon, M. E., Gendrault, J. L., Royer, C., Jaeck, D., Kirn, A., and Steffan, A. M. (1993). Human endothelial cells isolated from the hepatic sinusiods and the umbilical vein display a different permissiveness for HIV-1. Res. Virol. 144:99–104.

    Article  PubMed  CAS  Google Scholar 

  • Lehto, V. P., and Virtanen, I. (1983). Immunolocalization of a novel, cytoskeleton-associated polypeptide of Mr 230,000 daltons (p230). J. Cell Biol. 96:703–716.

    Article  PubMed  CAS  Google Scholar 

  • Li, A., Sakagchi, S., Shigematsu, K., Atarashi, R., Roy, B. C., Nakaoke, R., Arima, K., Okimura, N., Kopacek, J., and Katamine, S. (2000). Physiological expression of the gene for PrP-like protein, PrPLP/Dpl, by brain endothelial cells and its ectopic expression in neurons of PrP-deficient mice ataxic due to Purkinje cell degeneration. Am. J. Pathol. 157:1447–1452.

    PubMed  CAS  Google Scholar 

  • Lipton, S. A. (1991). HIV-related neurotoxicity. Brain Pathol. 1:193–199.

    Article  PubMed  CAS  Google Scholar 

  • Lossinsky, A. S., Pluta, R., Song, M. J., Badmajew, V., Moretz, R. C., and Wisniewski, H. M. (1991). Mechanisms of inflammatory cell attachment in chronic relapsing experimental allergic encephalomyelitis: A scanning and high-voltage electron microscopic study of the injured mouse blood–brain barrier. Microvasc. Res. 41:299–310.

    Article  PubMed  CAS  Google Scholar 

  • Mankowski, J. L., Spelman, J. P., Ressetar, H. G., Strandberg, J. D., Leterra, J., Carter, D. L., Clements, J. E., and Zink, M. C. (1999). Neurovirulent simian immunodeficiency virus replicated productively in endothelial cells of the central nervous system in vivo and in vitro. J. Virol. 68:8202–8208.

    Google Scholar 

  • Marcus, C. D., Taylor-Robinson, S. D., Sargentoni, J., Ainsworth, J. G., Frize, G., Easterbrook, P. J., Shaunak, S., and Bryant, D. J. (1998). 1H MR spectroscopy of the brain in HIV-1-seropositive subjects: Evidence for diffuse metabolic abnormalities. Met. Brain Dis. 13:123–136.

    Article  CAS  Google Scholar 

  • Marsh, M. (1984). The entry of enveloped viruses into cells by endocytosis. Biochem. J. 218:1–10.

    PubMed  CAS  Google Scholar 

  • McKeating, J. A., McKnight, A., and Moore, J. P. (1991). Differential loss of envelope glycoprotein gp120 from virions of human immunodeficiency virus type 1 isolates: Effects on infectivity and neutralization. J. Virol. 65:852–860.

    PubMed  CAS  Google Scholar 

  • Mehta, R., Zingde, S., Advani, S., Desai, H., and Gothoskar, B. (1999). Protein 1a: A major wheat germ agglutinin binding protein on the surface of human granulocytes associated with the cytoskeleton. Mol. Cell. Biochem. 144:153–165.

    Article  Google Scholar 

  • Mellman, I., Fuchs, R., and Helenius, A. (1986). Acidification of the endocytic and exocytic pathways. Ann. Rev. Biochem. 55:663–700.

    Article  PubMed  CAS  Google Scholar 

  • Moses, A. V., Bloom, F. E., Pauza, C. D., and Nelson, J. A. (1993). Human immunodeficiency virus infection of human brain capillary endothelial cells occurs via a CD4/galactosylceramide-independent mechanism. Proc. Natl Acad. Sci. USA 90:10474–10478.

    Article  PubMed  CAS  Google Scholar 

  • Moses, A. V., and Nelson, J. A. (1994). HIV infection of human brain capillary endothelial cells-implications for AIDS dementia. Adv. Neuroimmunol. 4:239–247.

    Article  PubMed  CAS  Google Scholar 

  • Moses, A. V., Stenglein, S. G., Strussenberg, J. G., Wehrly, K., Chesebro, B., and Nelson, J. A. (1996). Sequences regulating tropism of human immunodeficiency virus type 1 for brain capillary endothelial cells map to a unique region of the viral genome. J. Virol. 70:3401–3406.

    PubMed  CAS  Google Scholar 

  • Nakaoke, R., Sakaguchi, S., Atarashi, R., Nishida, N., Arima, K., Shigematsu, K., and Katamine, S. (2000). Early appearance but lagged accumulation of detergent-insoluble prion protein in the brains of mice inoculated with a mouse-adapted Creutzfeldt-Jakob disease agent. Cell. Mol. Neurobiol. 20:717–720.

    Article  PubMed  CAS  Google Scholar 

  • Nishida, N., Katamine, S., Shigematsu, K., Nakatani, A., Sakamoto, N., Hasegawa, S., Nakaoke, R., Atarashi, R., Kataoka, Y., and Miyamoto, T. (1997). Prion protein is necessary for latent learning and long-term memory retention. Cell. Mol. Neurobiol. 17:537–545.

    Article  PubMed  CAS  Google Scholar 

  • Nottet, H. S., Persidsky, Y., Sasseville, V. G., Nukuna, A. N., Bock, P., Zhai, Q. H., Sharer, L. R., McComb, R. D., Swindells, S., Soderland, C., and Gendelman, H. E. (1996). Mechanisms for the transendothelial migration of HIV-1-infected monocytes into brain. J. Immunol. 156:1284–1295.

    PubMed  CAS  Google Scholar 

  • Oster, S., Christoffersen, P., Gundersen, H. J., Nielsen, J. O., Pakkenberg, B., and Pedersen, C. (1993) Cerebral atrophy in AIDS: A stereological study. Acta Neuropathol. 85:617–622.

    Article  PubMed  CAS  Google Scholar 

  • Persidsky, Y., Stins, M., Way, D., Witte, M. H., Weinand, M., Kim, K. S., Bock, P., Gendelman, H. E., and Fiala, M. (1997). A model for monocyte migration through the blood–brain barrier during HIV-1 encephalitis. J. Immunol. 158:3499–3510.

    PubMed  CAS  Google Scholar 

  • Pleskoff, O., Sol, N., Labrosse, B., and Alizon, M. (1997a). Human immunodeficiency virus strains differ in their ability to infect CD4+ cells expressing the rat homolog of CXCR-4 (fusin). J. Virol. 71:3259–3262.

    CAS  Google Scholar 

  • Pleskoff, O., Treboute, C., Brelot, A., Heveker, N., Seman, M., and Alizon, M. (1997b). Identification of a chemokine receptor encoded by human cytomegalovirus as a cofactor for HIV-1 entry. Science 276:1874–1878.

    Article  CAS  Google Scholar 

  • Poland, S. D., Rice, G. P., and Dekaban, G. A. (1995a). HIV-1 infection of human brain-derived microvascular endothelial cells in vitro. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. 8:437–445.

    Article  CAS  Google Scholar 

  • Poland, S. D., Dekaban, G. A., Costello, P. C., Rice, G. P. (1995b). Cytomegalovirus-caused release of collagenase IV from human cerebral microvascular endothelial cells. Clin. Diagn. Virol. 4:301–309.

    Article  CAS  Google Scholar 

  • Poleshchuk, N. N., Votyakov, V. I., Ilkevich, Yu G., Duboiskaya, G. P., Grigoriev, D. G., and Kolomiets, N. D. (1992). Structural and functional changes of blood–brain barrier and indication of prion amyloid filaments in experimental amyotrophic leucospongiosis. Acta Virol. 36:293–303.

    PubMed  CAS  Google Scholar 

  • Prusiner, S. B. (1982). Novel proteinaceous infectious particles cause scrapie. Science 216:136–144.

    Article  PubMed  CAS  Google Scholar 

  • Prusiner, S. B. (1998). Prions. Proc. Natl Acad. Sci. USA 95:13363–13383.

    Article  PubMed  CAS  Google Scholar 

  • Prusiner, S. B., Groth, D. F., Bolton, D. C., Kent, S. B., and Hood, L. E. (1984). Purification and structural studies of a major scrapie prion protein. Cell 38:127–134.

    Article  PubMed  CAS  Google Scholar 

  • Raeissi, S., and Audus, K. L. (1989). In-vitro characterization of blood–brain barrier permeability to delta sleep-inducing peptide. Ann. N Y Acad. Sci. 41:848–852.

    CAS  Google Scholar 

  • Resnick, L., Berger, J., Shapshak, P., and Tourtellotte, W. W. (1988). Early penetration of the blood–brain-barrier by HIV. Neurology 38:9–14.

    PubMed  CAS  Google Scholar 

  • Salmivirta, M., Lidholt, K., and Lindahl, U. (1996). Heparan sulfate: A piece of information. FASEB J. 10:1270–1279.

    PubMed  CAS  Google Scholar 

  • Salmona, M., Malesani, P., De Gioia, L., Gorla, S., Bruschi, M., Molinari, A., Della Vedova, F., Pedrotti, B., Marrari, M. A., Awan, T., Bugiani, O., Gorloni, G., and Tagliavini, F. (1999) Molecular determinants of the physicochemical properties of a critical prion protein region comprising residues 106–126. Biochem. J. 342:207–214.

    Article  PubMed  CAS  Google Scholar 

  • Sakaguchi, S., Katamine, S., Nishida, N., Moriuchi, R., Shigematsu, K., Sugimoto, T., Nakatani, A., Kataoka, Y., Houtani, T., Shirabe, S., Okada, H., Hasegawa, S., Miyamoto, T., and Noda, T. (1996) Loss of cerebellar Purkinje cells in aged mice homozygous for a disrupted PrP gene. Nature 380:528–531.

    Article  PubMed  CAS  Google Scholar 

  • Sjolander, A., and Magnusson, K. E. (1988). Effects of wheat germ agglutinin on the cellular content of filamentous actin in Intestine 407 cells. Eur. J. Cell Biol. 47:32–35.

    PubMed  CAS  Google Scholar 

  • Steinman, J. L., Komisaruk, B. R., Pert, C., and Ruff, M. (1993). Monoparesis induced by gp-120 administered intrathecally in rats. Int. Conf. AIDS 9:193.

    Google Scholar 

  • Strelow, L. I., Watry, D. D., Fox, H. S., and Nelson, J. A. (1998). Efficient infection of brain microvascular endothelial cells by an in vivo-selected neuroinvasive SIVmac variant. J. Neurovirol. 4:269–280.

    Article  PubMed  CAS  Google Scholar 

  • Suchard, S. J. and Boxer, L. A. (1989). Characterization and cytoskeletal association of a major cell surface glycoprotein, GP 140, in human neutrophils. J. Clin. Invest. 84:484–492.

    Article  PubMed  CAS  Google Scholar 

  • Vitkovic, L., da Cunha, A., and Tyor, W. R. (1994). Cytokine expression and pathogenesis in AIDS brain. In Price, R. W., and Perry, S. W. (eds.), HIV, AIDS and the Brain, Raven Press Ltd., New York, pp 203–221.

    Google Scholar 

  • Weissmann, C., Enari, M., Klohn, P. C., Rossi, D., and Flechsig, D. (2002). Transmission of Prions. Proc. Natl. Acad. Sci. USA. 99:16378–16683.

    Article  PubMed  CAS  Google Scholar 

  • Westergren, I., and Johansson, B. B. (1993). Altering the blood–brain barrier in the rat by intracarotid nfusion of polycations: A comparison between protamine, poly-L-lysine and poly-L-arginine. Acta Physiol. Scand. 149:99–104.

    Article  PubMed  CAS  Google Scholar 

  • Wiley, C. A., Schrier, R. D., Nelson, J. A., Lampert, P. W., and Oldstone, M. B. A. (1986). Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients. Proc. Natl. Acad. Sci. USA 83:7089–7093.

    Article  PubMed  CAS  Google Scholar 

  • Willey, R. L., Martin, M. A., and Peden, K. W. C. (1994). Increase in soluble CD4 binding to and CD4-induced dissociation of gp120 from virions correlates with infectivity of human immunodeficiency virus type 1. J. Virol. 68:1029–1039.

    PubMed  CAS  Google Scholar 

  • Winslow, B. J., and Trono, D. (1993). The blocks to human immunodeficiency virus type 1 Tat and Rev functions in mouse cell lines are independent. J. Virol. 67:2349–2354.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology 1, Nagasaki University School of Medicine, Nagasaki, Japan

    Ryota Nakaoke

  2. Department of Internal Medicine, Division of Geriatrics, GRECC, Veterans Affairs Medical Center, Saint Louis University School of Medicine, St. Louis, Missouri

    Ryota Nakaoke & William A Banks

  3. WAB, 915 N. Grand Blvd, St. Louis, Missouri, 63106

    William A Banks

Authors
  1. Ryota Nakaoke
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. William A Banks
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to William A Banks.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nakaoke, R., Banks, W.A. In Vitro Methods in the Study of Viral and Prion Permeability Across the Blood–Brain Barrier. Cell Mol Neurobiol 25, 171–181 (2005). https://doi.org/10.1007/s10571-004-1381-z

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-004-1381-z

Key words

Search

Navigation