Histochemical changes of NADPH-diaphorase in Guillain–Barre syndrome

Abstract

The distribution of NADPH-diaphorase activity in peripheral nerve biopsy was studied to evaluate the role of nitric oxide in demyelination. NO is an important inflammatory mediator which appears to exert significant effects in number of demyelinating diseases, and sometimes is established a direct causal link between NO and demyelination. Till now there wasn’t any description for the involvement of nitric oxide in GBS cellular immune reactions. We have studied cellular and subcellular histochemistry of NADPHdiaphorase in GBS. Peripheral nerve biopsy tissues were examined with regard to disease duration, from 6 patients who were 11 to 52 days after onset of symptoms. Tetrazolium method in our modification was used to visualize NADPHdiaphorase reaction in the successive tissue sections on the cellular and ultrastructural levels. We have shown that specific pattern of histochemical reaction was characteristic for each distinct time point of disease duration. Up and downregulation mode of histochemical reaction was different for Schwann cells (SC) and mononuclear inflammatory cells. During demyelination reduced NADPH-diaphorase activity was found in SCs associated with degrading myeline sheath. During remyelination that characterized by proliferation of SCs and enlarge of its cell volume we observed an increase in NADPH-diaphorase reaction that indicated on the rise of the NO production in it. In that activated SCs the intracellular distribution of NADPH-diaphorase is changed. Maximum of reaction intensity was shifted in nucleus. It suggests the appearance of the expressional regulation in SCs, which characteristic for the highoutput iNOS, and directed to increase of NO production The levels of NADPH-diaphorase activity varied in large extend in different recruited macrophages in the same tissue sample. It reflects the cyclic character proper to macrophagal iNOS. Intensive reaction was found in cytoplasm and nuclear envelop of the mononuclear cells, that migrate throw the blood vessel walls where NO may enhancing local nerve blood flow and serve simultaneously as important effector in the clearance of the myelin/axonal debris. High intensive NADPH-diaphorase activity was detected in distinct cytoplasm regions of the macrophage on the territory of the injured myelin sheath. Hyperproduction of nitric oxide and cytotoxic effect may take place in such districts. All this findings suggest that endogenous nitric oxide is involved in pathogenesis of GBS.

About the authors

A. V. Sakharova

Research Center of Neurology

Author for correspondence.
Email: platonova@neurology.ru
Russian Federation

S. M. Lozhnikova

Research Center of Neurology

Email: platonova@neurology.ru
Russian Federation

M. A. Piradov

Research Center of Neurology

Email: platonova@neurology.ru
Russian Federation

V. N. Pirogov

Research Center of Neurology

Email: platonova@neurology.ru
Russian Federation

References

  1. Ванин А.Ф. Оксид азота – универсальный регулятор биологических процессов. NO-терапия: теоретические аспекты, клинический опыт и проблемы применения экзогенного оксида азота в медицине. Материалы научно-практической конференции 4 – 5 декабря 2001 года. Москва, 2001: 22 –27.
  2. Пирадов. М.А. Синдром Гийена–Барре. М.: Интермедика, 2003.
  3. Сахарова А.В., Ложникова С.М., Пирогов В.Н., Пирадов М.А. Экспрессия NADPH-диафоразы в периферическом нерве и ее изменение на разных стадиях дифтерийной полинейропатии. Архив патологии 1999; 61 (1): 39–46 (4).
  4. Сахарова А.В., Ложникова С.М. Ультраструктурная локализация NO-синтазной NADPH-диафоразы в периферическом нерве и ее изменения при дифтерийной полинейропатии. Вестник Российской академии медицинских наук 2000; 4: 44–48.
  5. Турпаев К.Т. Роль окиси азота в передаче сигнала между клетка- ми. Молекулярная биология 1998; 32 (4): 581–591.
  6. Birchem R., Mithen F.A., L’Empereur K.M. Ultrastructural effects of Guillain-Barre serum in cultures containing only rat Schwann cells and dorsal root ganglion neurons. Brain Res. 1987; 421 (1–2): 173–85.
  7. Brennder T., Brocke S., Szafer F., Sobel R.A., Parkinson J.F., Perez D.H., Steinman L. Inhibition of nitric oxide synthase for treatment of experimental autoimmune encephalomyelitis. J. Immunol. 1997; 158: 2940–2946.
  8. Conti G., Rostami A., Scarpini E., Baron P.L., Galimberti D., Bresolin N., Contri M., Palumbo C., De Pol A. Indusible nitric oxide synthase (iNOS) in immune№mediated demyelination and Wallerian degeneration of rat peripheral nervous system. Exp. Neurol. 2004; 187: 350–358.
  9. De Groot C.J., Ruuls S.R., Theeuwes J.W., Dijkstra C.D., van der Valk P. Immunocytochemical characterization of the expression of inducible and constitutive isoforms of nitric oxide synthase in demyelinating multiple sclerosis lesions. J. Neuropathol. Exp. Neurol. 1997; 56: 10–20.
  10. Ding M., Merril J.E. The kinetics and regulation of the induction of type II nitric oxide synthase and nitric oxide in human fetal glial cell cultures. Mol. Psychiatry 1997; 2 (2): 117–129.
  11. Dreyer J., Schleicher M., Tappe A., Schilling K., Kuner T., Kusumawidijaja G., Miller Esterl W., Oess S., Kuner R. Nitric oxide synthase (NOS)№interacting protein interacts with neuronal NOS and regulates its distribution and activity. J. Neurosci. 2004; 24 (46): 10454–10465.
  12. Elphick M.R. Localization of nitric oxide synthase using NADPH diaphorase histochemistry. Cell Tissue Res. 1995; 279 (2): 405–409.
  13. Felts P.A., Woolston M.A., Fernando H.B., Asquith S., Gregson N.A., Mizzi O.J., Smith R.J. Inflammation and primary demyelination induced by the intraspinal injection of lipopolysaccharide. Brain 2005 (Jul); 128 (Pt. 7): 1649–1666. Epub. 2005; May 4.
  14. Forstermann U., Boissel J P., Kleinert H. Expressional control of the `constitutive` isoforms of nitric oxide synthase (NOS I and NOS III). REWIEW. The FASEB Journal 1998; 12: 773–790.
  15. Garthwaite G., Batchelor A.M., Goodwin D.A., Hewson A.K., Leeming K., Ahmed Z., Cuzner M.L., Garthwait J. Pathological implication of iNOS expression in central white matter: an ex vivo study of optic nerves from rats with experimental allergic encephalomyelitis. Eur. J. Neurosci. 2005; 21 (8): 2127–2135.
  16. Gilchrist M., McCauley S.D., Befus A.D. Expression, localization, and regulation of human mast cell lines: effects on leucotriene production. Blood 2004; 104 (2): 462–469.
  17. Giordano A., Tonello C., Bulbarelli A., Cozzi V., Cinti S., Carrubo M.O., Nosoli E. Evidence for a functional nitric oxide synthase system in brown adipocyte nucleus. FEBS LETT 2002 (Mar. 13); 514 (2–3): 135–140.
  18. Gonzales Hernandez T., Rustioni A. Expression of three forms of nitric oxide synthase in peripheral nerve regeneration. J. Neurosci. Res. 1999; 55(2): 198–207.
  19. Keilhoff G., Fansa Y., Wolf G. Neuronal NOS deficiency promotes apoptotic cell death of spinal cord neurons after peripheral nerve tran- section. Nitric Oxide 2004; 10 (2): 101–111.
  20. Keilhoff G., Wolf G., Fansa H. NO-mediated differences in peripheral nerve graft revascularization and regeneration. Neuroreport 2002; 13 (11): 1463 –1468.
  21. Kennedy J.M., Zochodne D.W. Impaired peripheral nerve regeneration in diabetes mellitus. J. Peripher. Nerve Syst. 2005; 10 (2): 144–157.
  22. Michel T., Feron O. Nitric oxide synthases: which, where, how and why? J. Clin. Invest. 1997; 100 (9): 2146–2157.
  23. Nagano S., Takeda M., Ma L., Soliven B. Cytokine-induced cell death in immortalized Schwann cells: roles of nitric oxide and cyclic AMP. J. Neurochem. 2001; 77(6): 1486–1495.
  24. Saini R., Patel S., Saluja R., Sahasrabuddhe A.A., Singh P.M., Habib S., Bajpai V.K., Dikshit M. Nitric oxide synthase localisation in the rat neutrophils: immunocytochemical, molecular, and biochemical studies. Journal of Leukocyte Biology 2006; 79: 519–528.
  25. Smith K.J., Kapoor R., Felts P.A. Demyelination: The role of reactive oxygen and Nitrogen Species. Brain Pathology 1999; 9: 69–92, Symposium: Oxidative Stress in Neurological Disease.
  26. Wanschitz J., Maier H., Lassmann H., Budka and Berger T. Distinct time pattern of complement activation and cytotoxic T-cell response in Guillain№Barre syndrome. Brain 2003; 126 (9): 2034–2042.
  27. Zochodne D.W., Levi D. Delayed axonal degeneration and regeneration in mice lacking immunological (inducible) nitric oxide synthase (iNOS). Mechanisms of nerve degeneration and regeneration. Abstracts. Platform 1999 (Jule 24); 8.
  28. Zochodne D.W., Verge V.M.K., Cheng C., Hoke A., Jolley C., Thomsen K., Rubin J., Lauritzen M. Nitric oxide synthase activity and expression in experimental diabetic neuropathy. J. Neuropathol. Exp. Neurol. 2000; 59: 798–807.

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Copyright (c) 2017 Sakharova A.V., Lozhnikova S.M., Piradov M.A., Pirogov V.N.

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