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Ultrastructural and histophysiological studies on the blood-nerve barrier and perineurial barrier in leprosy neuropathy

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Summary

Onset and nature of ultrastructural changes in endoneurial vasa nervorum during the pathogenesis of leprosy neuropathy and possibly associated alterations in the “blood-nerve barrier” were investigated, together with perineurial barrier functioning, in mice infected 20–28 months previously withMycobacterium leprae and in (ageing) non-infected mice. Barriers were tested by i.v. administration of markers (Trypan blue and ferritin) 1–4 days before killing the mice.

Twenty-eight months after infection, histopathology of sciatic nerves was comparable to that seen in sensory nerves in clinically early human (borderline-) lepromatous leprosy. Schwann cells and endoneurial macrophages were bacillated, endothelia of endoneurial vessels not, and the perineurium rarely.

Many infected mice and all (ageing) controls possessed ultrastructurally and functionally normal endoneurial vessels. Their continuous endothelium with close junctions had prevented marker passage, even when surrounding endoneurial tissue cells were quite heavily bacillated. The perineurium was also normal.

By contrast, in infected mice showing hind limb paralysis serious histopathologic involvement and large globi of bacilli intrafascicularly in sciatic nerves, endoneurial blood vessels were abnormal. Open endothelial junctions, extreme attenuation, fenestrations, and luminal protrusions were all features comparable to neural microangiopathy encountered in leprosy patients (Boddingius 1977a, b). The “blood-nerve barrier” clearly had become defective allowing excessive exudation of Trypan blue and ferritin, via four pathways from the vessel lumen, deep into surrounding endoneurial tissues but halted by a normal perineurial barrier. Markers in such “blue” nerves were not found in bacillated or non-bacillated Schwann cells, thus denying significant phagocytotic and lysosomal activities of Schwann cells at this stage of neuropathy. Possible implications of barrier performances for anti-leprosy drug treatment of patients are discussed.

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References

  • Bakay L (1968) Changes in barrier effect in pathological states. In: Lajtha A, Ford DH (eds) Brain barrier systems. Elsevier, Amsterdam London New York, pp 315–341

    Google Scholar 

  • Bigotte L, Olsson Y (1983) Cytotoxic effects of adriamycin on mouse hypoglossal neurons following retrograde axonal transport from the tongue. Acta Neuropathol (Berl) 61:161–168

    Google Scholar 

  • Bigotte L, Arvidson B, Olsson Y (1982a) Cytofluorescence localisation of adriamycin in the nervous system. I. Distribution of the drug in the central nervous system of normal adult mice after intravenous injection. Acta Neuropathol (Berl) 57:121–129

    Google Scholar 

  • Bigotte L, Arvidson B, Olsson Y (1982b) Cytofluorescence localisation of adriamycin in the nervous system. II. Distribution of the drug in the somatic and autonomic peripheral nervous systems of normal adult mice after intravenous injection. Acta Neuropathol (Berl) 57:130–136

    Google Scholar 

  • Boddingius J (1974) The occurrence ofMycobacterium leprae within axons of peripheral nerves. Acta Neuropathol (Berl) 27:257–270

    Google Scholar 

  • Boddingius J (1976) Ultrastructural changes in blood vessels of peripheral nerves in leprosy neuropathy. I. Tuberculoid and borderline-tuberculoid leprosy patients. Acta Neuropathol (Berl) 35:159–181

    Google Scholar 

  • Boddingius J (1977a) Ultrastructural changes in blood vessels of peripheral nerves in leprosy neuropathy. II. Borderline, borderline-lepromatous, and lepromatous leprosy patients. Acta Neuropathol (Berl) 40:21–39

    Google Scholar 

  • Boddingius J (1977b) Ultrastructural and histophysiological changes in vasa nervorum of patients and mice with leprosy neuropathy. PhD Thesis, Oxford, UK

  • Boddingius J (1979) Ultrastructure of beginning and of progressive nerve involvement in leprosy patients. In: Latapi F, Saúl A, Rodríguez O, Malacara M, Browne SG (eds) Int Congr Ser 466, Leprosy. Excerpta Medica Elsevier North Holland/Proc XIth Int Lepr Congr, Mexico City, Nov 13–18, 1978, pp 271–276

  • Boddingius J (1981) Mechanisms of nerve damage in leprosy. In: Humber DP (ed) Immunological aspects of leprosy, tuberculosis and leishmaniasis. Int Congr Ser 574. Excerpta Medica, Elsevier Amsterdam, pp 64–73

    Google Scholar 

  • Boddingius J (1982) Mechanisms of peripheral nerve damage in leprosy: electron and light microscope studies in patients throughout the spectrum. In: Nunzi E, Browne SG (eds) Proc Eur Leprosy Symp, Santa Margherita Ligure, Genoa, Italy, May 1–3, 1981, pp 65–85

  • Boddingius J, Fallaux EM (1970) Argyrophil adenohypophysial cells in the rainbow trout (Salmo irideus), demonstrated simultaneously with chromophil cells and with intracellular argyrophil fibrils by a new technique. Neth J Zool 20:291–297

    Google Scholar 

  • Boddingius J, Stolz E (1981) Do anti-leprosy drugs reachMycobacterium leprae in peripheral nerves? Lancet I, 8223:774–775

    Google Scholar 

  • Boddingius J, Verdaasdonk M (1984) Immunocytochemical studies on anti-leprosy drugs in tissues. Ultramicroscopy (in press)

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

    Google Scholar 

  • Boddingius J, deBruijn WC, Verdaasdonk MAM (1983) Microanalytical (TEM) investigations on the presence of antileprosy drugs (DDS and Clofazimine) in Araldite-embedded liver and peripheral nerves. In: Pfefferkorn C (ed) Beiträge zur elektronenmikroskopischen Direktabbildung von Oberflächen (BEDO) Bd 16. Remy, Münster, pp 489–496

    Google Scholar 

  • Brightman MW (1965) The distribution within the brain of ferritin injected into the cerebrospinal fluid compartments. II. Parenchymal distribution. Am J Anat 117:193–220

    Google Scholar 

  • Cervos-Navarro J, Betz E, Matakar F, Wüllenweber R (1976) The cerebral vessel wall. Proc Erwin Riesch Symp, Berlin 1975. Raven Press, New York

    Google Scholar 

  • Cliff WJ (1976) Blood vessels. Cambridge University Press, Cambridge London New York

    Google Scholar 

  • Florey HW (1970) General pathology. Lloyd-Luke, London

    Google Scholar 

  • Ford DH (1968) Changes in brain accumulation of amino acids and adenine associated with changes in the physiologic state. In: Lajtha A, Ford DH (eds) Brain barrier systems. Elsevier, Amsterdam London New York, pp 401–415

    Google Scholar 

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

    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 

  • Krücke W (1941) Ödem und seröse Entzündung im peripheren Nerven. Virchows Arch 308:1–13

    Google Scholar 

  • Lajtha A, Ford DH (1968) Conclusions. In: Lajtha A, Ford DH (eds) Brain barrier systems. Elsevier, Amsterdam London New York, pp 535–537

    Google Scholar 

  • Lampert P, Garro FJ, Pentschew A (1970) Tellurium neuropathy. Acta Neuropathol (Berl) 15:308–317

    Google Scholar 

  • Nagy Z, Feters H, Hüttner I (1981) Endothelial surface changes: blood brain barrier opening to horseradish peroxidase induced by the polycation protamin sulfate. Acta Neuropathol [Suppl] (Berl) 7:7–9

    Google Scholar 

  • Ohnishi A, Schilling K, Brimijoin WS, Lambert EH, Fairbanks VF, Dyck PJ (1977) Lead neuropathy. 1. Morphometry, nerve conduction and choline acetyltransferase transport: new finding of endoneurial edema associated with segmental demyelination. J Neuropathol Exp Neurol 36:499–518

    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 (1967) Phylogenetic variations in the vascular permeability of peripheral nerves to serum albumin. Acta Pathol Microbiol Scand 69:621–623

    Google Scholar 

  • Olsson Y (1968) Studies on vascular permeability in peripheral nerves. III. Permeability changes of vasa nervorum and exudation of serum albumin in INH-induced neuropathy of the rat. Acta Neuropathol (Berl) 11:103–112

    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 

  • Pallie W, Pease DC (1958) Prefixation use of hyaluronidase to improve in situ preservation for electron microscopy. J Ultrastruct Res 2:1–7

    Google Scholar 

  • Quadbeck G (1968a) Clinical importance of alterations in barrier. In: Lajtha A, Ford DH (eds) Brain barrier systems. Elsevier, Amsterdam London New York

    Google Scholar 

  • Quadbeck G (1968b) Drug influence on the barrier. In: Lajtha A, Ford DH (eds) Brain barrier systems. Elsevier, Amsterdam London New York

    Google Scholar 

  • Rapoport SI (1976) Blood-brain barrier in physiology and medicine. Raven Press, New York

    Google Scholar 

  • Reynolds ES (1963) The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J Cell Biol 17:208–212

    Google Scholar 

  • Riley RW, Levy L (1973) Characteristics of the binding of dapsone and monoacetyl dapsone by serum albumin. Proc Soc Exp Biol Med 142:1168–1170

    Google Scholar 

  • Romeis B (1968) Mikroskopische Technik, Aufl 16. Oldenbourg, München Wien

    Google Scholar 

  • Seneviratne KN (1972) Permeability of blood nerve barriers in the diabetic rat. J Neurol Neurosurg Psychiatry 35:156–162

    Google Scholar 

  • Shamboorov DA, Tchibukmakher NB (1938) Contributions to the problem of the peripheral nervous barrier. Acta Med Scand 97:175–206

    Google Scholar 

  • Tschirgi RD (1950) Protein complexes and the impermeability of the blood-brain barrier to dyes. Am J Physiol 163:756

    Google Scholar 

  • Tschirgi RD (1962) Blood-brain barrier: fact or fancy? Fed Proc 21:665–671

    Google Scholar 

  • Waksman BH (1961) Experimental studies of diphtheritic polyneuritis in the rabbit and guinea pig. III. The bloodnerve barrier in the rabbit. J Neuropathol Exp Neurol 20:35–77

    Google Scholar 

  • Wheeler EA, Hamilton EG, Harman DJ (1965) An improved technique for the histopathological diagnosis and classification of leprosy. Leprosy Rev 36:37–39

    Google Scholar 

Download references

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Authors and Affiliations

  1. Dept. of Human Anatomy, University of Oxford, UK

    J. Boddingius

  2. Dept. of Dermatology, Research, Medical Faculty, Erasmus University, Hoogbouw 20, P.O. Box 1738, 3000 DR, Rotterdam, The Netherlands

    J. Boddingius

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Supported by the British Medical Research Council (MRC), the British Leprosy Relief Association (LEPRA), the Wellcome Trust, and the Netherlands Leprosy Relief Association (NSL)

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Boddingius, J. Ultrastructural and histophysiological studies on the blood-nerve barrier and perineurial barrier in leprosy neuropathy. Acta Neuropathol 64, 282–296 (1984). https://doi.org/10.1007/BF00690394

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  • DOI: https://doi.org/10.1007/BF00690394

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