Structural and Functional Characteristics of the Human Blood-Nerve Barrier with Translational Implications to Peripheral Nerve Autoimmune Disorders

  • Eroboghene E. UboguEmail author
Part of the Contemporary Clinical Neuroscience book series (CCNE)


Peripheral nerves and nerve roots comprise of three structural compartments: the outer epineurium consisting of longitudinal arrays of collagen fibers responsible for structural integrity and the inner perineurium consisting of multiple concentric layers of specialized epithelioid myofibroblasts that surround the innermost endoneurium which consists of myelinated and unmyelinated axons embedded in a looser mesh of collagen fibers. Axons are responsible for signal transduction to and from the central nervous system required for normal physiological processes and are targeted by the immune system in autoimmune disorders. A highly regulated endoneurial microenvironment is required for normal axonal function. This is achieved by tight junction-forming endoneurial microvessels that control ion, solute, water, nutrient, macromolecule and leukocyte influx and efflux between the bloodstream and endoneurium, and the innermost layers of the perineurium that control interstitial fluid component flux between the epineurium and endoneurium. Endoneurial microvascular endothelium is considered the blood-nerve barrier (BNB) due to direct communication with circulating blood. The mammalian BNB is considered the second most restrictive vascular system after the blood-brain barrier (BBB). Guided by human in vitro studies using primary and immortalized endoneurial endothelial cells that form the BNB, in situ studies in normal and pathologic human peripheral nerves, and representative animal models of peripheral nerve autoimmune disorders, knowledge is emerging on human BNB molecular and functional characteristics, including its array of cytokines/cytokine receptors, selectins, and cellular adhesion and junctional complex molecules that may be employed during normal immune surveillance and altered in autoimmune diseases, providing potential targets of efficacious immunotherapy.


BNB Endoneurium Immune system Leukocyte trafficking Peripheral nerve 



Blood-brain barrier


Blood-nerve barrier


Chronic inflammatory demyelinating polyradiculoneuropathy


Distal sensory polyneuropathy


Experimental autoimmune neuritis


Fluorescein isothiocyanate


Guillain-Barré syndrome


Glial-derived neurotrophic factor


Hypoxia-inducing factors


Human immunodeficiency virus


Human leukocyte antigen


Intercellular adhesion molecule-1








Mitogen-activated protein kinase


“rearranged upon transformation”


Ribonucleic acid


Spontaneous autoimmune peripheral polyneuropathy


Transendothelial electrical resistance


Transforming growth factor-β


Vascular cell adhesion molecule-1


Vascular endothelial cell growth factor


Zonula occludens


Acknowledgments and Funding

Special thanks to past and current employees of the Shin J Oh Muscle and Nerve Histopathology Laboratory, the University of Alabama at Birmingham, for processing human tissue and generating histopathology slides from which digital photomicrographs are shown and current and past members and collaborators of the Neuromuscular Immunopathology Research Laboratory (NIRL) for digital photomicrographs and ultramicrographs of human cells and tissues and mouse tissues. Work described from the NIRL was supported by National Institutes of Health Grants R21 NS073702 (2011–2014), R21 NS078226 (2012–2015), R01 NS075212 (2012–2018), and a Creative and Novel Ideas in HIV Research Subaward P30 AI27767 (2012-2015), as well as institutional support from the Department of Neurology, the University of Alabama at Birmingham. The content is solely the responsibility of the author and does not necessarily represent the official views of the National Institutes of Health.


  1. 1.
    Olsson Y. Microenvironment of the peripheral nervous system under normal and pathological conditions. Crit Rev Neurobiol. 1990;5:265–311.PubMedGoogle Scholar
  2. 2.
    Reina MA, Lopez A, Villanueva MC, de Andres JA, Leon GI. [Morphology of peripheral nerves, their sheaths, and their vascularization]. Rev Esp Anestesiol Reanim. 2000;47:464–475.Google Scholar
  3. 3.
    Reina MA, Lopez A, Villanueva MC, De Andres JA, Maches F. [The blood-nerve barrier in peripheral nerves]. Rev Esp Anestesiol Reanim. 2003;50:80–86.Google Scholar
  4. 4.
    Mizisin AP, Weerasuriya A. Homeostatic regulation of the endoneurial microenvironment during development, aging and in response to trauma, disease and toxic insult. Acta Neuropathol. 2011;121:291–312.PubMedCrossRefGoogle Scholar
  5. 5.
    Bell MA, Weddell AG. A descriptive study of the blood vessels of the sciatic nerve in the rat, man and other mammals. Brain J Neurol. 1984;107(Pt 3):871–98.CrossRefGoogle Scholar
  6. 6.
    Monk KR, Feltri ML, Taveggia C. New insights on Schwann cell development. Glia. 2015;63:1376–93.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Yosef N, Xia RH, Ubogu EE. Development and characterization of a novel human in vitro blood-nerve barrier model using primary endoneurial endothelial cells. J Neuropathol Exp Neurol. 2010;69:82–97.PubMedCrossRefGoogle Scholar
  8. 8.
    Sladjana UZ, Ivan JD, Bratislav SD. Microanatomical structure of the human sciatic nerve. Surg Radiol Anat. 2008;30:619–26.PubMedCrossRefGoogle Scholar
  9. 9.
    Yuan F, Yosef N, Lakshmana Reddy C, Huang A, Chiang SC, Tithi HR, Ubogu EE. CCR2 gene deletion and pharmacologic blockade ameliorate a severe murine experimental autoimmune neuritis model of Guillain-Barre syndrome. PLoS One. 2014;9:e90463.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Tanaka K, Webster HD. Myelinated fiber regeneration after crush injury is retarded in sciatic nerves of aging mice. J Comp Neurol. 1991;308:180–7.PubMedCrossRefGoogle Scholar
  11. 11.
    Christensen MB, Tresco PA. Differences exist in the left and right sciatic nerves of naive rats and cats. Anat Rec (Hoboken). 2015;298:1492–501.CrossRefGoogle Scholar
  12. 12.
    Ochoa J, Mair WG. The normal sural nerve in man. I. Ultrastructure and numbers of fibres and cells. Acta Neuropathol. 1969;13:197–216.PubMedCrossRefGoogle Scholar
  13. 13.
    Olsson Y. Studies on vascular permeability in peripheral nerves. I. Distribution of circulating fluorescent serum albumin in normal, crushed and sectioned rat sciatic nerve. Acta Neuropathol. 1966;7:1–15.PubMedCrossRefGoogle Scholar
  14. 14.
    Olsson Y. Topographical differences in the vascular permeability of the peripheral nervous system. Acta Neuropathol. 1968;10:26–33.PubMedCrossRefGoogle Scholar
  15. 15.
    Olsson Y. Studies on vascular permeability in peripheral nerves. IV. Distribution of intravenously injected protein tracers in the peripheral nervous system of various species. Acta Neuropathol. 1971;17:114–26.PubMedCrossRefGoogle Scholar
  16. 16.
    Hultstrom D, Malmgren L, Gilstring D, Olsson Y. FITC-Dextrans as tracers for macromolecular movements in the nervous system. A freeze-drying method for dextrans of various molecular sizes injected into normal animals. Acta Neuropathol. 1983;59:53–62.PubMedCrossRefGoogle Scholar
  17. 17.
    Poduslo JF, Curran GL, Berg CT. Macromolecular permeability across the blood-nerve and blood-brain barriers. Proc Natl Acad Sci U S A. 1994;91:5705–9.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Shimizu F, Sano Y, Abe MA, Maeda T, Ohtsuki S, Terasaki T, Kanda T. Peripheral nerve pericytes modify the blood-nerve barrier function and tight junctional molecules through the secretion of various soluble factors. J Cell Physiol. 2011;226:255–66.PubMedCrossRefGoogle Scholar
  19. 19.
    Shimizu F, Sano Y, Saito K, Abe MA, Maeda T, Haruki H, Kanda T. Pericyte-derived glial cell line-derived neurotrophic factor increase the expression of claudin-5 in the blood-brain barrier and the blood-nerve barrier. Neurochem Res. 2012;37:401–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Ubogu EE. The molecular and biophysical characterization of the human blood-nerve barrier: current concepts. J Vasc Res. 2013;50:289–303.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Kanda T, Numata Y, Mizusawa H. Chronic inflammatory demyelinating polyneuropathy: decreased claudin-5 and relocated ZO-1. J Neurol Neurosurg Psychiatry. 2004;75:765–9.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Palladino SP, Helton ES, Jain P, Dong C, Crowley MR, Crossman DK, Ubogu EE. The human blood-nerve barrier transcriptome. Sci Rep. 2017;7:17477.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Pummi KP, Heape AM, Grenman RA, Peltonen JT, Peltonen SA. Tight junction proteins ZO-1, occludin, and claudins in developing and adult human perineurium. J Histochem Cytochem. 2004;52:1037–46.PubMedCrossRefGoogle Scholar
  24. 24.
    Muller WA. Leukocyte-endothelial-cell interactions in leukocyte transmigration and the inflammatory response. Trends Immunol. 2003;24:327–34.PubMedGoogle Scholar
  25. 25.
    Hartsock A, Nelson WJ. Adherens and tight junctions: structure, function and connections to the actin cytoskeleton. Biochim Biophys Acta. 2008;1778:660–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Dejana E, Orsenigo F, Molendini C, Baluk P, McDonald DM. Organization and signaling of endothelial cell-to-cell junctions in various regions of the blood and lymphatic vascular trees. Cell Tissue Res. 2009;335:17–25.PubMedCrossRefGoogle Scholar
  27. 27.
    Cichon C, Sabharwal H, Ruter C, Schmidt MA. MicroRNAs regulate tight junction proteins and modulate epithelial/endothelial barrier functions. Tissue Barriers. 2014;2:e944446.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Stamatovic SM, Johnson AM, Keep RF, Andjelkovic AV. Junctional proteins of the blood-brain barrier: new insights into function and dysfunction. Tissue Barriers. 2016;4:e1154641.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Sluysmans S, Vasileva E, Spadaro D, Shah J, Rouaud F, Citi S. The role of apical cell-cell junctions and associated cytoskeleton in mechanotransduction. Biol Cell. 2017;109:139–61.PubMedCrossRefGoogle Scholar
  30. 30.
    Yosef N, Ubogu EE. GDNF restores human blood-nerve barrier function via RET tyrosine kinase-mediated cytoskeletal reorganization. Microvasc Res. 2012;83:298–310.PubMedCrossRefGoogle Scholar
  31. 31.
    Reddy CL, Yosef N, Ubogu EE. VEGF-A165 potently induces human blood-nerve barrier endothelial cell proliferation, angiogenesis, and wound healing in vitro. Cell Mol Neurobiol. 2013;33:789–801.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Yosef N, Ubogu EE. An immortalized human blood-nerve barrier endothelial cell line for in vitro permeability studies. Cell Mol Neurobiol. 2013;33:175–86.PubMedCrossRefGoogle Scholar
  33. 33.
    Trupp M, Ryden M, Jornvall H, Funakoshi H, Timmusk T, Arenas E, Ibanez CF. Peripheral expression and biological activities of GDNF, a new neurotrophic factor for avian and mammalian peripheral neurons. J Cell Biol. 1995;130:137–48.PubMedCrossRefGoogle Scholar
  34. 34.
    Naveilhan P, ElShamy WM, Ernfors P. Differential regulation of mRNAs for GDNF and its receptors Ret and GDNFR alpha after sciatic nerve lesion in the mouse. Eur J Neurosci. 1997;9:1450–60.PubMedCrossRefGoogle Scholar
  35. 35.
    Dong C, Ubogu EE. GDNF enhances human blood-nerve barrier function in vitro via MAPK signaling pathways. Tissue Barriers 2018;6(4):1–22.PubMedCrossRefGoogle Scholar
  36. 36.
    Muona P, Jaakkola S, Salonen V, Peltonen J. Expression of glucose transporter 1 in adult and developing human peripheral nerve. Diabetologia. 1993;36:133–40.PubMedCrossRefGoogle Scholar
  37. 37.
    Latker CH, Shinowara NL, Miller JC, Rapoport SI. Differential localization of alkaline phosphatase in barrier tissues of the frog and rat nervous systems: a cytochemical and biochemical study. J Comp Neurol. 1987;264:291–302.PubMedCrossRefGoogle Scholar
  38. 38.
    Cohen-Kashi Malina K, Cooper I, Teichberg VI. Closing the gap between the in-vivo and in-vitro blood-brain barrier tightness. Brain Res. 2009;1284:12–21.PubMedCrossRefGoogle Scholar
  39. 39.
    Lippmann ES, Azarin SM, Kay JE, Nessler RA, Wilson HK, Al-Ahmad A, Palecek SP, Shusta EV. Derivation of blood-brain barrier endothelial cells from human pluripotent stem cells. Nat Biotechnol. 2012;30:783–91.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Lippmann ES, Al-Ahmad A, Azarin SM, Palecek SP, Shusta EV. A retinoic acid-enhanced, multicellular human blood-brain barrier model derived from stem cell sources. Sci Rep. 2014;4:4160.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Wang YI, Abaci HE, Shuler ML. Microfluidic blood-brain barrier model provides in vivo-like barrier properties for drug permeability screening. Biotechnol Bioeng. 2017;114:184–94.PubMedCrossRefGoogle Scholar
  42. 42.
    Poduslo JF, Curran GL, Dyck PJ. Increase in albumin, IgG, and IgM blood-nerve barrier indices in human diabetic neuropathy. Proc Natl Acad Sci U S A. 1988;85:4879–83.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Rechthand E, Rapoport SI. Regulation of the microenvironment of peripheral nerve: role of the blood-nerve barrier. Prog Neurobiol. 1987;28:303–43.PubMedCrossRefGoogle Scholar
  44. 44.
    Rechthand E, Smith QR, Rapoport SI. Transfer of nonelectrolytes from blood into peripheral nerve endoneurium. Am J Physiol. 1987;252:H1175–82.PubMedGoogle Scholar
  45. 45.
    Helton ES, Palladino S, Ubogu EE. A novel method for measuring hydraulic conductivity at the human blood-nerve barrier in vitro. Microvasc Res. 2017;109:1–6.PubMedCrossRefGoogle Scholar
  46. 46.
    Ley K, Laudanna C, Cybulsky MI, Nourshargh S. Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol. 2007;7:678–89.PubMedCrossRefGoogle Scholar
  47. 47.
    Man S, Ubogu EE, Ransohoff RM. Inflammatory cell migration into the central nervous system: a few new twists on an old tale. Brain Pathol. 2007;17:243–50.PubMedCrossRefGoogle Scholar
  48. 48.
    Muller WA. How endothelial cells regulate transmigration of leukocytes in the inflammatory response. Am J Pathol. 2014;184:886–96.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Mempel TR, Scimone ML, Mora JR, von Andrian UH. In vivo imaging of leukocyte trafficking in blood vessels and tissues. Curr Opin Immunol. 2004;16:406–17.PubMedCrossRefGoogle Scholar
  50. 50.
    Pai S, Danne KJ, Qin J, Cavanagh LL, Smith A, Hickey MJ, Weninger W. Visualizing leukocyte trafficking in the living brain with 2-photon intravital microscopy. Front Cell Neurosci. 2012;6:67.PubMedGoogle Scholar
  51. 51.
    Teixeira MM, Vilela MC, Soriani FM, Rodrigues DH, Teixeira AL. Using intravital microscopy to study the role of chemokines during infection and inflammation in the central nervous system. J Neuroimmunol. 2010;224:62–5.PubMedCrossRefGoogle Scholar
  52. 52.
    Zenaro E, Rossi B, Angiari S, Constantin G. Use of imaging to study leukocyte trafficking in the central nervous system. Immunol Cell Biol. 2013;91:271–80.PubMedCrossRefGoogle Scholar
  53. 53.
    Dong C, Greathouse KM, Beacham RL, Palladino SP, Helton ES, Ubogu EE. Fibronectin connecting segment-1 peptide inhibits pathogenic leukocyte trafficking and inflammatory demyelination in experimental models of chronic inflammatory demyelinating polyradiculoneuropathy. Exp Neurol. 2017;292:35–45.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Greathouse KM, Palladino SP, Dong C, Helton ES, Ubogu EE. Modeling leukocyte trafficking at the human blood-nerve barrier in vitro and in vivo geared towards targeted molecular therapies for peripheral neuroinflammation. J Neuroinflammation. 2016;13:3.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Yosef N, Ubogu EE. alpha(M)beta(2)-integrin-intercellular adhesion molecule-1 interactions drive the flow-dependent trafficking of Guillain-Barre syndrome patient derived mononuclear leukocytes at the blood-nerve barrier in vitro. J Cell Physiol. 2012;227:3857–75.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Kanda T. Biology of the blood-nerve barrier and its alteration in immune mediated neuropathies. J Neurol Neurosurg Psychiatry. 2013;84:208–12.PubMedCrossRefGoogle Scholar
  57. 57.
    Kanda T, Yamawaki M, Mizusawa H. Sera from Guillain-Barre patients enhance leakage in blood-nerve barrier model. Neurology. 2003;60:301–6.PubMedCrossRefGoogle Scholar
  58. 58.
    Shimizu F, Sawai S, Sano Y, Beppu M, Misawa S, Nishihara H, Koga M, Kuwabara S, Kanda T. Severity and patterns of blood-nerve barrier breakdown in patients with chronic inflammatory demyelinating polyradiculoneuropathy: correlations with clinical subtypes. PLoS One. 2014;9:e104205.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Dong C, Palladino SP, Helton ES, Ubogu EE. The pathogenic relevance of alphaM-integrin in Guillain-Barre syndrome. Acta Neuropathol. 2016;132:739–52.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Bosetti F, Galis ZS, Bynoe MS, Charette M, Cipolla MJ, Del Zoppo GJ, Gould D, Hatsukami TS, Jones TL, Koenig JI, Lutty GA, Maric-Bilkan C, Stevens T, Tolunay HE, Koroshetz W. Small Blood Vessels: Big Health Problems Workshop P: “Small Blood Vessels: Big Health Problems?”: Scientific Recommendations of the National Institutes of Health Workshop. J Am Heart Assoc. 2016:5.Google Scholar
  61. 61.
    Ubogu EE. Inflammatory neuropathies: pathology, molecular markers and targets for specific therapeutic intervention. Acta Neuropathol. 2015;130:445–68.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Eames RA, Lange LS. Clinical and pathological study of ischaemic neuropathy. J Neurol Neurosurg Psychiatry. 1967;30:215–26.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Dalakas MC. Pathogenesis of immune-mediated neuropathies. Biochim Biophys Acta. 2015;1852:658–66.PubMedCrossRefGoogle Scholar
  64. 64.
    Mathey EK, Park SB, Hughes RA, Pollard JD, Armati PJ, Barnett MH, Taylor BV, Dyck PJ, Kiernan MC, Lin CS. Chronic inflammatory demyelinating polyradiculoneuropathy: from pathology to phenotype. J Neurol Neurosurg Psychiatry. 2015;Google Scholar
  65. 65.
    Ziganshin RH, Ivanova OM, Lomakin YA, Belogurov AA Jr, Kovalchuk SI, Azarkin IV, Arapidi GP, Anikanov NA, Shender VO, Piradov MA, Suponeva NA, Vorobyeva AA, Gabibov AG, Ivanov VT, Govorun VM. The pathogenesis of the demyelinating form of Guillain-Barre Syndrome (GBS): proteo-peptidomic and immunological profiling of physiological fluids. Mol Cell Proteomics. 2016;15:2366–78.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Matsumuro K, Izumo S, Umehara F, Osame M. Chronic inflammatory demyelinating polyneuropathy: histological and immunopathological studies on biopsied sural nerves. J Neurol Sci. 1994;127:170–8.PubMedCrossRefGoogle Scholar
  67. 67.
    Mitchell GW, Williams GS, Bosch EP, Hart MN. Class II antigen expression in peripheral neuropathies. J Neurol Sci. 1991;102:170–6.PubMedCrossRefGoogle Scholar
  68. 68.
    Steck AJ, Kinter J, Renaud S. Differential gene expression in nerve biopsies of inflammatory neuropathies. J Peripher Nerv Syst. 2011;16(Suppl 1):30–3.PubMedCrossRefGoogle Scholar
  69. 69.
    Orlikowski D, Chazaud B, Plonquet A, Poron F, Sharshar T, Maison P, Raphael JC, Gherardi RK, Creange A. Monocyte chemoattractant protein 1 and chemokine receptor CCR2 productions in Guillain-Barre syndrome and experimental autoimmune neuritis. J Neuroimmunol. 2003;134:118–27.PubMedCrossRefGoogle Scholar
  70. 70.
    Mathey EK, Pollard JD, Armati PJ. TNF alpha, IFN gamma and IL-2 mRNA expression in CIDP sural nerve biopsies. J Neurol Sci. 1999;163:47–52.PubMedCrossRefGoogle Scholar
  71. 71.
    Pollard JD, Baverstock J, McLeod JG. Class II antigen expression and inflammatory cells in the Guillain-Barre syndrome. Ann Neurol. 1987;21:337–41.PubMedCrossRefGoogle Scholar
  72. 72.
    Pollard JD, McCombe PA, Baverstock J, Gatenby PA, McLeod JG. Class II antigen expression and T lymphocyte subsets in chronic inflammatory demyelinating polyneuropathy. J Neuroimmunol. 1986;13:123–34.PubMedCrossRefGoogle Scholar
  73. 73.
    Putzu GA, Figarella-Branger D, Bouvier-Labit C, Liprandi A, Bianco N, Pellissier JF. Immunohistochemical localization of cytokines, C5b-9 and ICAM-1 in peripheral nerve of Guillain-Barre syndrome. J Neurol Sci. 2000;174:16–21.PubMedCrossRefGoogle Scholar
  74. 74.
    Lindenlaub T, Sommer C. Cytokines in sural nerve biopsies from inflammatory and non-inflammatory neuropathies. Acta Neuropathol. 2003;105:593–602.PubMedGoogle Scholar
  75. 75.
    Van Rhijn I, Van den Berg LH, Bosboom WM, Otten HG, Logtenberg T. Expression of accessory molecules for T-cell activation in peripheral nerve of patients with CIDP and vasculitic neuropathy. Brain J Neurol. 2000;123(Pt 10):2020–9.CrossRefGoogle Scholar
  76. 76.
    Kieseier BC, Tani M, Mahad D, Oka N, Ho T, Woodroofe N, Griffin JW, Toyka KV, Ransohoff RM, Hartung HP. Chemokines and chemokine receptors in inflammatory demyelinating neuropathies: a central role for IP-10. Brain J Neurol. 2002;125:823–34.CrossRefGoogle Scholar
  77. 77.
    Jones G, Zhu Y, Silva C, Tsutsui S, Pardo CA, Keppler OT, McArthur JC, Power C. Peripheral nerve-derived HIV-1 is predominantly CCR5-dependent and causes neuronal degeneration and neuroinflammation. Virology. 2005;334:178–93.PubMedCrossRefGoogle Scholar
  78. 78.
    Bosboom WM, Van den Berg LH, Mollee I, Sasker LD, Jansen J, Wokke JH, Logtenberg T. Sural nerve T-cell receptor Vbeta gene utilization in chronic inflammatory demyelinating polyneuropathy and vasculitic neuropathy. Neurology. 2001;56:74–81.PubMedCrossRefGoogle Scholar
  79. 79.
    Collins MP, Arnold WD, Kissel JT. The neuropathies of vasculitis. Neurol Clin. 2013;31:557–95.PubMedCrossRefGoogle Scholar
  80. 80.
    Engelhardt A, Lorler H, Neundorfer B. Immunohistochemical findings in vasculitic neuropathies. Acta Neurol Scand. 1993;87:318–21.PubMedCrossRefGoogle Scholar
  81. 81.
    Leppert D, Hughes P, Huber S, Erne B, Grygar C, Said G, Miller KM, Steck AJ, Probst A, Fuhr P. Matrix metalloproteinase upregulation in chronic inflammatory demyelinating polyneuropathy and nonsystemic vasculitic neuropathy. Neurology. 1999;53:62–70.PubMedCrossRefGoogle Scholar
  82. 82.
    Oka N, Kawasaki T, Mizutani K, Sugiyama H, Akiguchi I. Hypoxia-inducible factor 1alpha may be a marker for vasculitic neuropathy. Neuropathology. 2007;27:509–15.PubMedCrossRefGoogle Scholar
  83. 83.
    Probst-Cousin S, Neundorfer B, Heuss D. Microvasculopathic neuromuscular diseases: lessons from hypoxia-inducible factors. Neuromuscul Disord. 2010;20:192–7.PubMedCrossRefGoogle Scholar
  84. 84.
    Meyer zu Horste G, Hartung HP, Kieseier BC. From bench to bedside – experimental rationale for immune-specific therapies in the inflamed peripheral nerve. Nat Clin Pract Neurol. 2007;3:198–211.PubMedCrossRefGoogle Scholar
  85. 85.
    Schafflick D, Kieseier BC, Wiendl H, Meyer Zu Horste G. Novel pathomechanisms in inflammatory neuropathies. J Neuroinflammation. 2017;14:232.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Archelos JJ, Maurer M, Jung S, Miyasaka M, Tamatani T, Toyka KV, Hartung HP. Inhibition of experimental autoimmune neuritis by an antibody to the lymphocyte function-associated antigen-1. Lab Invest. 1994;70:667–75.PubMedGoogle Scholar
  87. 87.
    Zou LP, Pelidou SH, Abbas N, Deretzi G, Mix E, Schaltzbeerg M, Winblad B, Zhu J. Dynamics of production of MIP-1alpha, MCP-1 and MIP-2 and potential role of neutralization of these chemokines in the regulation of immune responses during experimental autoimmune neuritis in Lewis rats. J Neuroimmunol. 1999;98:168–75.PubMedCrossRefGoogle Scholar
  88. 88.
    Duan RS, Chen Z, Bao L, Quezada HC, Nennesmo I, Winblad B, Zhu J. CCR5 deficiency does not prevent P0 peptide 180-199 immunized mice from experimental autoimmune neuritis. Neurobiol Dis. 2004;16:630–7.PubMedCrossRefGoogle Scholar
  89. 89.
    Salomon B, Rhee L, Bour-Jordan H, Hsin H, Montag A, Soliven B, Arcella J, Girvin AM, Padilla J, Miller SD, Bluestone JA. Development of spontaneous autoimmune peripheral polyneuropathy in B7-2-deficient NOD mice. J Exp Med. 2001;194:677–84.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Ubogu EE, Yosef N, Xia RH, Sheikh KA. Behavioral, electrophysiological, and histopathological characterization of a severe murine chronic demyelinating polyneuritis model. J Peripher Nerv Syst. 2012;17:53–61.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Louvet C, Kabre BG, Davini DW, Martinier N, Su MA, DeVoss JJ, Rosenthal WL, Anderson MS, Bour-Jordan H, Bluestone JA. A novel myelin P0-specific T cell receptor transgenic mouse develops a fulminant autoimmune peripheral neuropathy. J Exp Med. 2009;206:507–14.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Neuromuscular Immunopathology Research Laboratory, Division of Neuromuscular Disease, Department of NeurologyUniversity of Alabama at BirminghamBirminghamUSA

Personalised recommendations