Skip to main content
SpringerLink
Log in

The mouse blood-brain barrier and blood-nerve barrier for IgG: A tracer study by use of the avidin-biotin system

  • Original Works
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Summary

To study the permeability of the blood-brain barrier (BBB) and the blood-nerve barrier (BNB) for immunoglobulin G (IgG) we adapted the avidin-biotin system for postembedding demonstration of the tracer IgG in the central and peripheral nervous system (CNS, PNS). Normal mouse and human IgG were biotinylated and injected daily into the intraperitoneal (i.p.) space of adult BDF1 mice. After 24 h, IgG was detected in blood vessels and in the interstitium of various organs, but staining was restricted to the dura mater in the CNS, to the spinal ganglia, and to the perineurium of peripheral nerves. After 4 days, IgG was also present in the endoneurial connective tissue of peripheral nerves, while the brain, spinal cord, and spinal roots remained free of IgG. Our results show a partial permeability of the normal mouse BNB for homologous and heterologous IgG.

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

  • Baver EA, Wilchek M, Skutelsky E (1976) Affinity cytochemistry: The localization of lectin and antibody receptors on erythrocytes via the avidon-biotin complex. FEBS Lett 68:240–244

    Google Scholar 

  • Besinger UA, Toyka KV, Anzil AP, Fateh-Moghadam A, Neumeier D, Rauscher R, Heininger K (1981) Myeloma neuropathy: Passive transfer from man to mouse. Science 213:1027–1030

    Google Scholar 

  • Boddingius J, Rees RJW, Weddell AGM (1972) Defects in the blood-nerve barrier in mice with leprosy neuropathy. Nature New Biol 237:190–191

    Google Scholar 

  • Brightman MW, Klatzo I, Olsson Y, Reese TS (1970) The blood-brain barrier to proteins under normal and pathological conditions. J Neurol Sci 10:215–239

    Google Scholar 

  • Dalakas MC, Engel WK (1981) Polyneuropathy with monoclonal gammopathy: Studies of 11 patients. Ann Neurol 10:45–52

    Google Scholar 

  • Farrell CL, Shivers RR (1984) Capillary junctions of the rat are not affected by osmotic opening of the blood-brain barrier. Acta Neuropathol (Berl) 63:179–189

    Google Scholar 

  • Feasby TE, Hahn AF, Gilbert JJ (1982) Passive transfer studies in Guillain-Barré polyneuropathy. Neurology (NY) 32: 1159–1167

    Google Scholar 

  • Felgenhauer K (1980) Protein filtration and secretion at human body fluid barriers. Eur J Physiol 385:9–17

    Google Scholar 

  • Goldstein GW, Betz AL (1983) Recent advances in understanding brain capillary function. Ann Neurol 14:389–395

    Google Scholar 

  • Green NM (1963) Avidin. 1. The use of (14C biotin for kinetic studies and for assay. Biochem J 89:585–591

    Google Scholar 

  • Grundke-Iqbal I, Lassmann H, Wisniewski HM (1980) Chronic relapsing experimental allergic encephalomyelitis. Immunohistochemical studies. Arch Neurol 37:651–656

    Google Scholar 

  • Guesdon J-L, Ternynck T, Avraneas S (1979) The use of avidinbiotin interaction in immunoenzymatic techniques. J Histochem Cytochem 27:1131–1139

    Google Scholar 

  • Gurney ME, Belton AC, Cashman N, Antel JP (1984) Inhibition of terminal axonal sprouting by serum from patients with amyotrophic lateral sclerosis. N Eng J Med 311:933–939

    Google Scholar 

  • Heggeness MH, Ash JF (1977) Use of the avidin-biotin complex for the localization of actin and myosin with fluorescence microscopy. J Cell Biol 73:783–788

    Google Scholar 

  • Heininger K, Liebert UG, Toyka KV, Haneveld FT, Schwendemann G, Kolb-Bachofen V, Ross H-G, Cleveland S, Besinger UA, Gibbels E, Wechsler W (1984) Chronic inflammatory polyneuropathy. Reduction of nerve conduction velocities in monkeys by systemic passive transfer of immunoglobulin. G. J Neurol Sci 66:1–14

    Google Scholar 

  • Hirano A, Becker NH, Zimmerman HM (1969) Pathological alterations in the cerebral endothelial cell barrier to peroxidase. Arch Neurol 20:300–308

    Google Scholar 

  • Hochwald GM, Wallenstein MC (1967) Exchange of gammaglobulin between blood, cerebrospinal fluid and brain in the cat. Exp Neurol 19:115–126

    Google Scholar 

  • Huang S-N (1975) Immunohistochemical demonstration of hepatitis B core and surface antigens in paraffin sections. Lab Invest 33:88–95

    Google Scholar 

  • Jacobs JM, MacFarlane RM, Cavanagh JB (1976) Vascular leakage in the dorsal root ganglia of the rat, studied with horseradish peroxidase. J Neurol Sci 29:95–107

    Google Scholar 

  • Kelly JJ, Kyle RA, O'Brien PC, Dyck PA (1981a) Prevalence of monoclonal protein in peripheral neuropathy. Neurology (NY) 31:1480–1483

    Google Scholar 

  • Kelly JJ, Kyle RA, Miles JM, O'Brien PC, Dyck PJ (1981b) The spectrum of peripheral neuropathy in myeloma. Neurology (NY) 31:24–31

    Google Scholar 

  • Kitz K, Lassmann H, Karcher D, Lowenthal A (1984) Blood-brain barrier in chronic relapsing experimental allergic encephalomyelitis: A correlative study between cerebrospinal fluid protein concentrations and tracer leakage in the central nervous system. Acta Neuropathol (Berl) 63:41–50

    Google Scholar 

  • Klemm H (1970) Das Perineurium als Diffusionsbarriere gegenüber Peroxydase bei epi-und endoneuraler Applikation. Z Zellforsch 108:431–445

    Google Scholar 

  • Krieger C, Melmed C (1982) Amyotrophic lateral sclerosis and paraproteinemia. Neurology (NY) 32:896–897

    Google Scholar 

  • Kristensson K, Olsson Y (1971) The perineurium as a diffusion barrier to protein tracers. Differences between mature and immature animals. Acta Neuropathol (Berl) 17:127–138

    Google Scholar 

  • Lee JC (1982) Anatomy of the blood-brain barrier under normal and pathological conditions. In: Haymaker W, Adams RD (eds) Histology and histopathology of the nervous system. Thomas, Springfield, IL, pp 798–870

    Google Scholar 

  • Liebert UG, Seitz RJ, Weber T, Wechsler W (1985) Immunocytochemical studies of serum proteins and immunoglobulins in human sural nerve biopsies. Acta Neuropathol (Berl) (in press)

  • Livrea P, Trojano M, Simone IL, Zimatore GB, Pisicchio L, Logroscino G, Cibelli G (1984) Heterogeneous models for blood-cerebrospinal fluid barrier permeability to serum proteins in normal and abnormal cerebrospinal fluid/serum protein concentration gradients. J Neurol Sci 64:245–258

    Google Scholar 

  • Martin KH (1964) Untersuchungen über die perineurale Diffusionsbarriere an gefriergetrockneten Nerven. Z Zellforsch 64:404–428

    Google Scholar 

  • Oldendorf WH, Cornford ME, Brown WJ (1977) The large apparent work capability of the blood-brain barrier: A study of the mitochondrial content of capillary endothelial cells in brain and other tissues of the rat. Ann Neurol 1:409–417

    Google Scholar 

  • Oldfors A, Johansson BR (1979) Barriers and transport properties of the perineurium. An ultrastructural study with125I-labeled albumin and horseradish peroxidase in normal and protein-deprived rats. Acta Neuropathol (Berl) 47:139–143

    Google Scholar 

  • Olsson Y (1966) Studies on vascular permeability in peripheral nerves. I. Distribution of circulating fluorescent serum albumin in normal, crushed and sectioned rat sciatic nerve. Acta Neuropathol (Berl) 7:1–15

    Google Scholar 

  • Olsson Y (1968) Topographic differences in the vascular permeability of the peripheral nervous system. Acta Neuropathol (Berl) 10:26–33

    Google Scholar 

  • Olsson Y (1971) Studies on vascular permeability in peripheral nerves. IV. Distribution of intravenously injected protein tracers in the peripheral nervous system of various species. Acta Neuropathol (Berl) 17:114–126

    Google Scholar 

  • Olsson Y, Reese TS (1971) Permeability of vasa nervorum and perineurium in mouse sciatic nerve studied by fluorescence and electron microscopy. J Neuropathol Exp Neurol 30:105–119

    Google Scholar 

  • Olsson Y (1975) Vascular permeability in the peripheral nervous system. In: Dyck PJ, Thomas PK, Lambert EH (eds) Peripheral neuropathy. Saunders, Philadelphia London Toronto, pp 190–200

    Google Scholar 

  • Reese TS, Karnovsky (1967) Fine structural localization of a blood-brain barrier to exogenous peroxidase. J Cell Biol 34:207–217

    Google Scholar 

  • Ryberg B, Baumann NA (1983) Different types of antibrain antibodies in multiple sclerosis. Studies employing myelin-deficient mutants of mice. J Neurol Sci 58:351–355

    Google Scholar 

  • Seil FJ, Westall FC, Romine JS, Salk J (1983) Serum demyelinating factors in multiple sclerosis. Ann Neurol 13:664–667

    Google Scholar 

  • Seitz RJ, Löhler J, Schwendemann G (1981) Ependyma and meninges of the spinal cord of the mouse. A light-and electron-microscopic study. Cell Tissue Res 220:61–72

    Google Scholar 

  • Spatz M, Mrsulja BB (1982) Progress in cerebral microvascular studies related to the function of the blood-brain barrier. Adv Cell Neurobiol 3:311–337

    Google Scholar 

  • Spurr AR (1969) A low-viscosity epoxy resin embedding medium for electron microscopy. J Ultrastruct Res 26:31–43

    Google Scholar 

  • Sternberger LA, Hardy PH, Cuculis JJ, Meyer HG (1970) The unlabeled antibody enzyme method of immunohistochemistry. Preparation and properties of soluble antigen-antibody complex (horseradish peroxidase-antihorseradish peroxidase) and its use in identification of spirochetes. J Histochem Cytochem 18:315–333

    Google Scholar 

  • Swash M, Perrin J, Schwartz MS (1979) Significance of immunoglobulin disposition in peripheral nerve in neuropathies associated with paraproteinaemia. J Neurol Neurosurg Psychiatry 42:179–183

    Google Scholar 

  • Waksman BH (1961) Experimental study of diphtheric polyneuritis in the rabbit and guinea pig. III. The blood-nerve barrier in the rabbit. J Neuropathol Exp Neurol 20:35–77

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dept. of Neuropathology, University of Düsseldorf, Moorenstraße 5, D-4000, Düsseldorf 1, Federal Republic of Germany

    R. J. Seitz & W. Wechsler

  2. Dept. Neurology, University of Düsseldorf, Moorenstraße 5, D-4000, Düsseldorf 1, Federal Republic of Germany

    K. Heininger, G. Schwendemann & K. V. Toyka

Authors
  1. R. J. Seitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K. Heininger
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. Schwendemann
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K. V. Toyka
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. W. Wechsler
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported by the Deutsche Forschungsgemeinschaft SFB 200, B 5 and C 1, and by the Ministerium MWF (North-Rhine Westphalia)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Seitz, R.J., Heininger, K., Schwendemann, G. et al. The mouse blood-brain barrier and blood-nerve barrier for IgG: A tracer study by use of the avidin-biotin system. Acta Neuropathol 68, 15–21 (1985). https://doi.org/10.1007/BF00688950

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00688950

Key words

Search

Navigation