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. 1988 Jul;85(13):4879–4883. doi: 10.1073/pnas.85.13.4879

Increase in albumin, IgG, and IgM blood-nerve barrier indices in human diabetic neuropathy.

J F Poduslo 1, G L Curran 1, P J Dyck 1
PMCID: PMC280540  PMID: 3387444

Abstract

The albumin (Alb), IgG, and IgM concentrations in the endoneurium of fascicular sural nerve biopsy samples were evaluated in controls (n = 9 or 10), diabetic patients without neuropathy (n = 6), and diabetic patients with polyneuropathy (n = 17 or 18). These values were significantly increased in diabetic patients with and without neuropathy when expressed both per endoneurial dry weight or endoneurial total protein compared to biopsy samples from healthy controls. When these concentrations, expressed per endoneurial total protein, were related to plasma concentrations similarly expressed, the resulting blood-nerve barrier (BNB) indices were significantly increased for Alb (6.1 times; P less than 0.00001), IgG (4.9 times; P = 0.00037), and IgM (2.7 times; P = 0.015). The diabetic patients without neuropathy (defined as having an index of pathology of greater than 0.65; a measure of the severity of the pathological abnormality based on morphological criteria) also had significant increases in two of these BNB indices that were intermediate between the diabetic neuropathy patients and controls (Alb, 3.9 times controls; P = 0.00002: IgG, 4.6 times controls; P = 0.00016: IgM, 1.8 times controls; not significant). No correlations were observed between the endoneurial concentrations of these plasma proteins or the BNB indices and the index of pathology, suggesting that these increases in endoneurial plasma proteins precede the pathologic alterations. The increased values for the diabetics in the absence of pathological abnormalities may prove useful in predicting neuropathic complications. The ratio of the IgG-BNB index to the Alb-BNB index was decreased 19%, and the ratio of the IgM-BNB index to the Alb-BNB index was decreased 56% in diabetic neuropathy patients compared to controls. Although the IgG and IgM concentrations are increased in the diabetic endoneurium, the Alb increase is greater and a mechanism other than size indiscriminate extravasation of plasma proteins, therefore, is suggested. Morphometric assessment of the endoneurial compartments, which would be expected to contain these plasma proteins, suggests that they are not altered in diabetic neuropathy; hence, it is hypothesized that the observed increase in endoneurial concentration of these plasma proteins results from altered transport through the endothelial or perineurial barrier, which supports an underlying vascular mechanism in the development of diabetic polyneuropathy.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arvidson B. Evidence for vesicular transport of horseradish peroxidase across endoneurial vessels of the sciatic nerve in normal mice. Acta Neuropathol. 1984;64(1):1–5. doi: 10.1007/BF00695598. [DOI] [PubMed] [Google Scholar]
  2. Brownlee M., Vlassara H., Cerami A. Trapped immunoglobulins on peripheral nerve myelin from patients with diabetes mellitus. Diabetes. 1986 Sep;35(9):999–1003. doi: 10.2337/diab.35.9.999. [DOI] [PubMed] [Google Scholar]
  3. Dyck P. J., Hansen S., Karnes J., O'Brien P., Yasuda H., Windebank A., Zimmerman B. Capillary number and percentage closed in human diabetic sural nerve. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2513–2517. doi: 10.1073/pnas.82.8.2513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dyck P. J., Karnes J. L., O'Brien P., Okazaki H., Lais A., Engelstad J. The spatial distribution of fiber loss in diabetic polyneuropathy suggests ischemia. Ann Neurol. 1986 May;19(5):440–449. doi: 10.1002/ana.410190504. [DOI] [PubMed] [Google Scholar]
  5. Dyck P. J., Lais A., Karnes J. L., O'Brien P., Rizza R. Fiber loss is primary and multifocal in sural nerves in diabetic polyneuropathy. Ann Neurol. 1986 May;19(5):425–439. doi: 10.1002/ana.410190503. [DOI] [PubMed] [Google Scholar]
  6. Ghitescu L., Fixman A., Simionescu M., Simionescu N. Specific binding sites for albumin restricted to plasmalemmal vesicles of continuous capillary endothelium: receptor-mediated transcytosis. J Cell Biol. 1986 Apr;102(4):1304–1311. doi: 10.1083/jcb.102.4.1304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Graham A. R., Johnson P. C. Direct immunofluorescence findings in peripheral nerve from patients with diabetic neuropathy. Ann Neurol. 1985 May;17(5):450–454. doi: 10.1002/ana.410170506. [DOI] [PubMed] [Google Scholar]
  8. HESS H. H., LEWIN E. MICROASSAY OF BIOCHEMICAL STRUCTURAL COMPONENTS IN NERVOUS TISSUES. II. METHODS FOR CEREBROSIDES, PROTEOLIPID PROTEINS AND RESIDUE PROTEINS. J Neurochem. 1965 Mar;12:205–211. doi: 10.1111/j.1471-4159.1965.tb06756.x. [DOI] [PubMed] [Google Scholar]
  9. Kumagai A. K., Eisenberg J. B., Pardridge W. M. Absorptive-mediated endocytosis of cationized albumin and a beta-endorphin-cationized albumin chimeric peptide by isolated brain capillaries. Model system of blood-brain barrier transport. J Biol Chem. 1987 Nov 5;262(31):15214–15219. [PubMed] [Google Scholar]
  10. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  11. Mata M., Staple J., Fink D. J. The distribution of serum albumin in rat peripheral nerve. J Neuropathol Exp Neurol. 1987 Jul;46(4):485–494. doi: 10.1097/00005072-198707000-00007. [DOI] [PubMed] [Google Scholar]
  12. Michel M. E., Shinowara N. L., Odman S., Rapoport S. I. Morphology of endoneurial blood vessels of frog sciatic nerve during vascular perfusion. Microvasc Res. 1984 Sep;28(2):220–232. doi: 10.1016/0026-2862(84)90019-0. [DOI] [PubMed] [Google Scholar]
  13. Milici A. J., Watrous N. E., Stukenbrok H., Palade G. E. Transcytosis of albumin in capillary endothelium. J Cell Biol. 1987 Dec;105(6 Pt 1):2603–2612. doi: 10.1083/jcb.105.6.2603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ohi T., Poduslo J. F., Curran G. L., Dyck P. J. Quantitative method for detection of blood-nerve barrier alterations in experimental animal models of neuropathy. Exp Neurol. 1985 Nov;90(2):365–372. doi: 10.1016/0014-4886(85)90025-1. [DOI] [PubMed] [Google Scholar]
  15. Ohi T., Poduslo J. F., Dyck P. J. Increased endoneurial albumin in diabetic polyneuropathy. Neurology. 1985 Dec;35(12):1790–1791. doi: 10.1212/wnl.35.12.1790. [DOI] [PubMed] [Google Scholar]
  16. Pardridge W. M., Eisenberg J., Cefalu W. T. Absence of albumin receptor on brain capillaries in vivo or in vitro. Am J Physiol. 1985 Sep;249(3 Pt 1):E264–E267. doi: 10.1152/ajpendo.1985.249.3.E264. [DOI] [PubMed] [Google Scholar]
  17. Pleasure D., Bora F. W., Jr, Lane J., Prockop D. Regeneration after nerve transection: effect of inhibition of collagen synthesis. Exp Neurol. 1974 Oct;45(1):72–78. doi: 10.1016/0014-4886(74)90101-0. [DOI] [PubMed] [Google Scholar]
  18. Poduslo J. F., Curran G. L., Brunden K. R., Dyck P. J. IgM/IgG solid-phase antibody-capture assay with biotin/125I-streptavidin amplification: application to normal human sural nerve biopsies. J Neuroimmunol. 1988 May;18(2):117–124. doi: 10.1016/0165-5728(88)90060-4. [DOI] [PubMed] [Google Scholar]
  19. Poduslo J. F., Low P. A., Nickander K. K., Dyck P. J. Mammalian endoneurial fluid: collection and protein analysis from normal and crushed nerves. Brain Res. 1985 Apr 15;332(1):91–102. doi: 10.1016/0006-8993(85)90392-0. [DOI] [PubMed] [Google Scholar]
  20. Poduslo J. F., Low P. A., Windebank A. J., Dyck P. J., Berg C. T., Schmelzer J. D. Altered blood-nerve barrier in experimental lead neuropathy assessed by changes in endoneurial albumin concentration. J Neurosci. 1982 Oct;2(10):1507–1514. doi: 10.1523/JNEUROSCI.02-10-01507.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Poduslo J. F. Regulation of myelination: biosynthesis of the major myelin glycoprotein by Schwann cells in the presence and absence of myelin assembly. J Neurochem. 1984 Feb;42(2):493–503. doi: 10.1111/j.1471-4159.1984.tb02705.x. [DOI] [PubMed] [Google Scholar]
  22. Powell H. C., Rosoff J., Myers R. R. Microangiopathy in human diabetic neuropathy. Acta Neuropathol. 1985;68(4):295–305. doi: 10.1007/BF00690832. [DOI] [PubMed] [Google Scholar]
  23. Rechthand E., Rapoport S. I. Regulation of the microenvironment of peripheral nerve: role of the blood-nerve barrier. Prog Neurobiol. 1987;28(4):303–343. doi: 10.1016/0301-0082(87)90006-2. [DOI] [PubMed] [Google Scholar]
  24. Rodbard D., Lewald J. E. Computer analysis of radioligand assay and radioimmunoassay data. Acta Endocrinol Suppl (Copenh) 1970;147:79–103. doi: 10.1530/acta.0.065s079. [DOI] [PubMed] [Google Scholar]
  25. Seitz R. J., Heininger K., Schwendemann G., Toyka K. V., Wechsler W. The mouse blood-brain barrier and blood-nerve barrier for IgG: a tracer study by use of the avidin-biotin system. Acta Neuropathol. 1985;68(1):15–21. doi: 10.1007/BF00688950. [DOI] [PubMed] [Google Scholar]
  26. Yasuda H., Dyck P. J. Abnormalities of endoneurial microvessels and sural nerve pathology in diabetic neuropathy. Neurology. 1987 Jan;37(1):20–28. doi: 10.1212/wnl.37.1.20. [DOI] [PubMed] [Google Scholar]

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