Summary
The leakage of eight different serum proteins and immunoglobulins across the blood-nerve barrier (BNB) was studied by means of the peroxidase-antiperoxidase method in hereditary and inflammatory neuropathies and graded semiquantitatively with respect to endoneurial staining intensity and distribution. These data were compared with the degree of alterations of the myelinated nerve fibre population evaluated by morphometric analysis. Our series of 18 human sural nerve biopsies included seven hereditary neuropathies (three HMSN I, two HMSN II, two tomaculous neuropathies), nine inflammatory neuropathies (seven polyneuritis, two hypertrophic neuritis) and two normal controls. In HMSN II and in tomaculous neuropathy there was no enhanced endoneurial staining for serum proteins despite of a severe nerve fibre loss, whereas in HMSN I a rise of serum proteins of small and moderate molecular size like albumin and IgG was demonstrated in the endoneurial space indicating an impaired BNB function. Qualitative changes of the BNB with leakage also of high molecular weight proteins were observed in polyneuritis and hypertrophic neuritis, irrespective of the degree of nerve fibre changes. Our results show that fibre loss and alteration of the BNB are not correlated. The unselective leakage of serum proteins through the BNB appears to be a characteristic change in inflammatory neuropathies leading to proteinous edema. With regard to the subperineurial accentuation of the endoneurial edema it will be discussed that the vascular diffusion barrier is more fragile than the perineurial diffusion barrier.
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References
Aoki Y, Miyatake T, Shimizu N, Yoshida M (1984) Medullasin activity in granulocytes of patients with multiple sclerosis. Ann Neurol 15:245–249
Asbury AK (1981) Diagnostic considerations in Guillain-Barré syndrome. Ann Neurol [Suppl] 9:1–5
Asbury AK, Arnason BG, Adams RD (1969) The inflammatory lesion in idiopathic polyneuritis. Its role in pathogenesis. Medicine (Baltimore) 48:173–215
Behse F, Buchthal F, Carlsen F, Knappeis GG (1972) Hereditary neuropathy with liability to pressure palsies. Electrophysiological and histopathological aspects. Brain 95:777–794
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
Boddingius J (1977) 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
Boddingius J (1984) Ultrastructural and histophysiological studies on the blood-nerve barrier and perineurial barrier in leprosy neuropathy. Acta Neuropathol (Berl) 64:282–296
Bouché P, Gherardi R, Cathala HP, Lhermitte F, Castaigne P (1983) Peroneal muscular atrophy. 1. Clinical and electrophysiological study. J Neurol Sci 61:389–399
De la Motte DJ, Hall SM, Allt G (1975) A study of the perineurium in peripheral nerve pathology. Acta Neuropathol (Berl) 33:257–270
Dolman CL, Allan BM (1973) Relapsing hypertrophic neuritis. Arch Neurol 28:351–353
Dyck PJ (1975) Definition and basis of classification of hereditary neuropathy with neuronal atrophy and degeneration. In: Dyck PJ, Thomas PK, Lambert EH (eds) Peripheral neuropathy. Saunders, Philadelphia London Toronto, pp 755–758
Dyck PJ, Arnason B (1984) Chronic inflammatory demyelinating polyradiculoneuropathy. In: Dyck PJ, Thomas PK, Lambert EH, Bunge R (eds) Peripheral neuropathies, 2nd edn. Saunders, Philadelphia London Toronto, pp 2101–2114
Dyck PJ, Lais AC, Ohta M, Bastron JA, Okazaki H, Groover RV (1975) Chronic inflammatory polyradiculoneuropathy. Mayo Clin Proc 50:621–637
Dyck PJ, Windebank AJ, Low PA, Bauman WJ (1980) Blood-nerve barrier in rat and cellular mechanisms of lead-induced segmental demyelination. J Neuropathol Exp Neurol 39:700–709
Felgenhauer K (1974a) Protein size and cerebrospinal fluid composition. Klin Wochenschr 52:1158–1164
Felgenhauer K (1974b) Evaluation of molecular size by gel electrophoresic techniques. Hoppe Seylers Z Physiol Chem 355:1281–1290
Gherardi R, Bouché P, Escourolle R, Hauw JJ (1983) Peroneal muscular atrophy. 2. Nerve biopsy studies. J Neurol Sci 61:401–416
Graham AR, Johnson PC (1985) Direct immunofluorescence findings in peripheral nerve from patients with diabetic neuropathy. Ann Neurol 17:450–454
Gutrecht JA, Dyck PJ (1970) Quantitative teased-fiber and histologic studies of human sural nerve during postnatal development. J Comp Neurol 138:117–129
Haferkamp G, Regli F (1976) Die sporadische rezidivierende hypertrophische Polyneuropathie. Klinisch-histologischer Beitrag zur Differentialdiagnose. Schweiz Arch Neurol Neurochir Psychiatr 118:7–22
Harris W, Newcomb WD (1929) A case of relapsing interstitial hypertrophic polyneuritis. Brain 52:108–116
Issekutz (1984) Role of polymorphonuclear leukocytes in the vascular responses of acute inflammation. Lab Invest 50:605–607
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
Klemm H (1970) Das Perineurium als Diffusionsbarriere gegenüber Peroxydase bei epi- und endoneuraler Applikation. Z Zellforsch Mikrosk Anat 108:431–445
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
Krücke W (1955) Erkrankungen des peripheren Nerven. Handb Spez Pathol Anat Histol. 13:1–2
Liebert UG, Seitz RJ, Weber T, Wechsler W (1985) Immunocytochemical studies of serum proteins and immunoglobulins in human sural nerve biopsies. Acta Neuropathol (Berl) 68:39–47
Low PA, Yao JK, Poduslo JF, Donald DE, Dyck PJ (1982) Peripheral nerve microenvironment: collection of endoneurially enriched fluid. Exp Neurol 77:208–214
Madrid R, Bradley WG (1975) The pathology of neuropathies with focal thickening of the myelin sheath (tomaculous neuropathy). Studies on the formation of the abnormal myelin sheath. J Neurol Sci 25:415–448
Malmgren LT, Olsson Y (1979) Early influx of horse-radish peroxidase into axons of the hypoglossal nerve during Wallerian degeneration. Neurosci Lett 13:13
Martin KH (1964) Untersuchungen über die perineurale Diffusionsbarriere an gefriergetrockneten Nerven. Z Zellforsch Mikrosk Anat 64:404–428
Mellick R, Cavanagh JB (1967a) Changes in blood vessel permeability during degeneration and regeneration in peripheral nerves. Brain 91:141–160
Mellick R, Cavanagh JB (1967b) Longitudinal movement of radioiodinated albumin within extravascular spaces of peripheral nerves following three systems of experimental trauma. J Neurol Neurosurg Psychiatry 30:458–463
Mellick RS, Cavanagh JB (1968) Changes in blood vessel permeability during degeneration and regeneration in peripheral nerves. Brain 41:141–160
Meyermann R, Linington C, Steigerwald U, Böhme D, Izumo S (1985) Passively induced EAN by P2 protein-specific T line cells: the role of edema. In: Clinical research unit for multiple sclerosis. Annual report, vol. 3. Max-Planck-Society, pp 122–126
Ochoa J, Mair WG (1968a) The normal sural nerve in man. I. Ultrastructural and numbers of fibres and cells. Acta Neuropathol (Berl) 13:197–216
Ochoa J, Mair WG (1969b) The normal sural nerve in man. II. Changes in the axons and Schwann cells due to ageing. Acta Neuropathol (Berl) 13:217–239
Ohi T, Poduslo JF, Dyck PJ (1985) Increased endoneurial albumin in diabetic polyneuropathy. Neurology 35:1790–1791
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
Oldfors A, Sourander P (1978) Barriers of peripheral nerve towards exogenous peroxidase in normal and protein deprived rats. Acta Neuropathol (Berl) 43:129–134
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
Olsson Y (1967) Degranulation of mast cells in peripheral nerve injuries. Acta Neurol Scand 43:365–374
Olsson Y (1968) Topographical differences in the vascular permeability of the peripheral nervous system. Acta Neuropathol (Berl) 10:26–33
Olsson JY (1971) Studies on vascular permeability in peripheral nerves. IV. Distribution of intravenous injected protein tracers in the peripheral nervous system of various species. Acta Neuropathol (Berl) 17:114–126
Olsson Y (1984) Vascular permeability in the peripheral nervous system. In: Dyck PJ, Thomas PK, Lambert EH, Bunge R (eds) Peripheral neuropathy, vol 1, 2nd edn. Saunders, Philadelphia London Toronto, pp 579–597
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
Pollock M, Nukada H, Allpress S, Calder C, Mackinnon M (1984) Peripheral nerve morphometry in stroke patients. J Neurol Sci 65:341–352
Powell HC, Myers RR, Costello ML, Lampert PW (1979) Endoneurial fluid pressure in Wallerian degeneration. Ann Neurol 5:550–559
Powell HC, Braheny SL, Myers RR, Rodriguez M, Lampert PW (1983) Early changes in experimental allergic neuritis. Lab Invest 48:332–338
Prineas JW (1971) Demyelination and remyelination in recurrent idiopathic polyneuropathy. An electron microscopic study. Acta Neuropathol (Berl) 18:34–57
Prineas JW (1981) Pathology of the Guillain-Barré syndrome. Ann Neurol [Suppl] 9:6–19
Seitz RJ, Heininger K, Schwendemann G, Toyka KV, Wechsler W (1985a) The mouse blood-brain barrier and blood-nerve barrier for IgG: a tracer study by use of the avidin-biotin system. Acta Neuropathol (Berl) 68:15–21
Seitz RJ, Neuen E, Wechsler (1985b) The blood-nerve barrier in polyneuritis: immunocytochemical and electron microscopical studies on the human sural nerve. J Neurol [Suppl] 232:244
Shamboorov DA, Tchibukmakher NB (1938) Contributions to the problem of the peripheral nervous barrier. Acta Med Scand 97:175–206
Shinowara NL, Michel ME, Papoport SI (1982) Morphological correlates of permeability in the frog perineurium: vesicles and “transcellular channels”. Cell Tissue Res 227:11–22
Söderfeldt B, Olsson Y, Kristonsson K (1973) The perineurium as a diffusion barrier to protein tracers in human peripheral nerve. Acta Neuropathol (Berl) 25:120–126
Sparrow JR, Kiernan JA (1981) Endoneurial vascular permeability in degenerating and regenerating peripheral nerves. Acta Neuropathol (Berl) 53:181–188
Van Lis JMJ, Jennekens FGI (1977) Plasma proteins in human peripheral nerve. J Neurol Sci 34:329–341
Waggener JD, Bunn SM, Beggs J (1965) The diffusion of ferritin within the peripheral nerve sheath: an electron microscopy study. J Neuropathol Exp Neurol 24:430–443
Waksman BH (1961) Experimental study of diphtheritic polyneuritis in the rabbit and guinea pig. III. The blood-nerve barrier in the rabbit. J Neuropathol Exp Neurol 20:35–77
Webster HdeF, Schröder JM, Asbury AK, Adams RD (1967) The role of Schwann cells in the formation of “onion bulbs” found in chronic neuropathies. J Neuropathol Exp Neurol 26:276–299
Weller RO, Herzog I (1970) Schwann cell lysosomes in hypertrophic neuropathy and in normal human nerves. Brain 93:347–356
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Dedicated to Professor Dr. W. Krücke on the occasion of his 75th birthday
Supported by the Deutsche Forschungsgemeinschaft (SFB 200)
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Neuen, E., Seitz, R.J., Langenbach, M. et al. The leakage of serum proteins across the blood-nerve barrier in hereditary and inflammatory neuropathies. Acta Neuropathol 73, 53–61 (1987). https://doi.org/10.1007/BF00695502
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DOI: https://doi.org/10.1007/BF00695502