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

SummaryTo 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.

[1]  L. Sternberger,et al.  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 , 1970, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[2]  H. Wiśniewski,et al.  Chronic relapsing experimental allergic encephalomyelitis. Immunohistochemical studies. , 1980, Archives of neurology.

[3]  B. Waksman.  Experimental study of diphtheritic polyneuritis in the rabbit and guinea pig. III. The bloodnerve barrier in the rabbit. , 1961, Journal of neuropathology and experimental neurology.

[4]  Huang Sn.  Immunohistochemical demonstration of hepatitis B core and surface antigens in paraffin sections. , 1975 .

[5]  R. Seitz,et al.  Immunocytochemical studies of serum proteins and immunoglobulins in human sural nerve biopsies , 2004, Acta Neuropathologica.

[6]  R. Rees,et al.  Defects in the blood-nerve barrier in mice with leprosy neuropathy. , 1972, Nature: New biology.

[7]  H. Lassmann,et al.  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 , 2004, Acta Neuropathologica.

[8]  G. Goldstein,et al.  Recent advances in understanding brain capillary function , 1983, Annals of neurology.

[9]  N. Green,et al.  AVIDIN. 1. THE USE OF (14-C)BIOTIN FOR KINETIC STUDIES AND FOR ASSAY. , 1963, The Biochemical journal.

[10]  Yngve Olsson,et al.  Topographical differences in the vascular permeability of the peripheral nervous system , 1968, Acta Neuropathologica.

[11]  W. Engel,et al.  Polyneuropathy with monoclonal gammopathy: Studies of 11 patients , 1981, Annals of neurology.

[12]  Helmut Flemm.  Das Perineurium als Diffusionsbarriere gegenüber Peroxydase bei epi- und endoneuraler Applikation , 2004, Zeitschrift für Zellforschung und Mikroskopische Anatomie.

[13]  K. Martin.  Untersuchungen über die perineurale Diffusionsbarriere an gefriergetrockneten Nerven , 1964, Zeitschrift für Zellforschung und Mikroskopische Anatomie.

[14]  Y. Olsson.  Studies on vascular permeability in peripheral nerves , 1966, Acta Neuropathologica.

[15]  H. Klemm.  [The perineurium: a diffusion barrier for peroxidase in epineurial and endoneurial application]. , 1970, Zeitschrift fur Zellforschung und mikroskopische Anatomie.

[16]  Thomas S. Reese,et al.  FINE STRUCTURAL LOCALIZATION OF A BLOOD-BRAIN BARRIER TO EXOGENOUS PEROXIDASE , 1967, The Journal of cell biology.

[17]  P. Dyck,et al.  Prevalence of monoclonal protein in peripheral neuropathy , 1981, Neurology.

[18]  H. Wiśniewski,et al.  Chronic relapsing experimental allergic encephalomyelitis , 1977, Acta Neuropathologica.

[19]  J. Jacobs,et al.  Vascular leakage in the dorsal root ganglia of the rat, studied with horseradish peroxidase , 1976, Journal of the Neurological Sciences.

[20]  M. Wallenstein,et al.  Exchange of albumin between blood, cerebrospinal fluid, and brain in the cat. , 1967, The American journal of physiology.

[21]  M. Heggeness,et al.  Use of the avidin-biotin complex for the localization of actin and myosin with fluorescence microscopy , 1977, The Journal of cell biology.

[22]  K. Felgenhauer.  Protein filtration and secretion at human body fluid barriers , 1980, Pflügers Archiv.

[23]  S. Cleveland,et al.  Chronic inflammatory polyneuropathy Reduction of nerve conduction velocities in monkeys by systemic passive transfer of immunoglobulin G , 1984, Journal of the Neurological Sciences.

[24]  J. Kimura,et al.  Far‐field somatosensory evoked potentials after stimulation of the tibial nerve , 1982, Neurology.

[25]  N. Baumann,et al.  Different types of antibrain antibodies in multiple sclerosis: Studies employing myelin-deficient mutants of mice , 1983, Journal of the Neurological Sciences.

[26]  J. Salk,et al.  Serum demyelinating factors in multiple sclerosis , 1983, Annals of neurology.

[27]  J. Vallat,et al.  Magnesium sulfate for AIP seizures , 1981, Neurology.

[28]  Y. Olsson.  Studies on vascular permeability in peripheral nerves , 2004, Acta Neuropathologica.

[29]  M. Wilchek,et al.  Affinity cytochemistry: The localization of lectin and antibody receptors on erythrocytes via the avidin‐biotin complex , 1976, FEBS letters.

[30]  Y. Olsson,et al.  The blood-brain barrier to proteins under normal and pathological conditions. , 1970, Journal of the neurological sciences.

[31]  A. Hirano,et al.  Pathological alterations in the cerebral endothelial cell barrier to peroxidase. , 1969, Archives of neurology.

[32]  A. Hirano,et al.  Pathological Alterations in the Cerebral , 1969 .

[33]  W. Oldendorf,et al.  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 , 1977, Annals of neurology.

[34]  R. Shivers,et al.  Capillary junctions of the rat are not affected by osmotic opening of the blood-brain barrier , 2004, Acta Neuropathologica.

[35]  K. Kristensson,et al.  The perineurium as a diffusion barrier to protein tracers , 1971, Acta Neuropathologica.

[36]  J. Guesdon,et al.  The use of avidin-biotin interaction in immunoenzymatic techniques. , 1979, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[37]  S. Huang.  Immunohistochemical demonstration of hepatitis B core and surface antigens in paraffin sections. , 1975, Laboratory investigation; a journal of technical methods and pathology.

[38]  R. Adams,et al.  EXPERIMENTAL STUDY OF DIPHTHERITIC POLYNEURITIS IN THE RABBIT AND GUINEA PIG , 1957, The Journal of experimental medicine.

[39]  A. Spurr.  A low-viscosity epoxy resin embedding medium for electron microscopy. , 1969, Journal of ultrastructure research.

[40]  M. Spatz,et al.  Progress in Cerebral Microvascular Studies Related to the Function of the Blood-Brain Barrier , 1982 .

[41]  M. Gurney,et al.  Inhibition of terminal axonal sprouting by serum from patients with amyotrophic lateral sclerosis. , 1984, The New England journal of medicine.

[42]  R. Seitz,et al.  Ependyma and meninges of the spinal cord of the mouse , 1981, Cell and Tissue Research.

[43]  G. Logroscino,et al.  Heterogeneous models for blood-cerebrospinal fluid barrier permeability to serum proteins in normal and abnormal cerebrospinal fluid/serum protein concentration gradients , 1984, Journal of the Neurological Sciences.

[44]  Y. Olsson,et al.  PERMEABILITY OF VASA NERVORUM AND PERINEURIUM IN MOUSE SCIATIC NERVE STUDIED BY FLUORESCENCE AND ELECTRON MICROSCOPY , 1971, Journal of neuropathology and experimental neurology.

[45]  B. Johansson,et al.  Barriers and transport properties of the perineurium , 1979, Acta Neuropathologica.

[46]  C. Melmed,et al.  Amyotrophic lateral sclerosis and paraproteinemia , 1982, Neurology.

[47]  Webb Haymaker,et al.  Histology and Histopathology of the Nervous System , 1982 .

[48]  K. Toyka,et al.  Myeloma neuropathy: passive transfer from man to mouse. , 1981, Science.