Аксональная дегенерация и вторичная демиелинизация в центральной и периферической нервной системе
Аксональная дегенерация и вторичная демиелинизация в центральной и периферической нервной системе
Ковражкина Е.А., Стаховская Л.В., Разинская О.Д. Аксональная дегенерация и вторичная демиелинизация в центральной и периферической нервной системе. Consilium Medicum. 2016; 18 (9): 87–91. DOI: 10.26442/2075-1753_2016.9.87-91
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Kovrazhkina E.A., Stahovskaya L.V., Razinskaya O.D. Axonal degeneration and secondary demyelization in the central and peripheral nervous system. Consilium Medicum. 2016; 18 (9): 87–91. DOI: 10.26442/2075-1753_2016.9.87-91
Аксональная дегенерация и вторичная демиелинизация в центральной и периферической нервной системе
Ковражкина Е.А., Стаховская Л.В., Разинская О.Д. Аксональная дегенерация и вторичная демиелинизация в центральной и периферической нервной системе. Consilium Medicum. 2016; 18 (9): 87–91. DOI: 10.26442/2075-1753_2016.9.87-91
________________________________________________
Kovrazhkina E.A., Stahovskaya L.V., Razinskaya O.D. Axonal degeneration and secondary demyelization in the central and peripheral nervous system. Consilium Medicum. 2016; 18 (9): 87–91. DOI: 10.26442/2075-1753_2016.9.87-91
Введение. Известно, что течение валлеровской дегенерации, регенерации аксонов после повреждения, вторичной демиелинизации, а также скорость и качество восстановления нервных волокон после повреждения различны в центральной и периферической нервной системе. Цель – сравнительная оценка выраженности аксонопатии и вторичной демиелинизации у пациентов с миелопатиями и заболеваниями периферической нервной системы. Методы. Обследованы 115 пациентов с миелопатиями разного генеза и срока давности (основная группа), 70 больных с диабетической периферической сенсомоторной полинейропатией (группа сравнения 1) и 90 пациентов с боковым амиотрофическим склерозом (группа сравнения 2). Сегментарное (во всех группах) и надсегментарное (в группах основной и сравнения 2) моторные исследования проводились методами электронейромиографии и транскраниальной магнитной стимуляции. Течение заболевания оценивалось по специализированным количественным шкалам при катамнестическом наблюдении через 3 мес после первичного обследования (FIM – в основной группе, NDS – в группе сравнения 1, ALSFRS-R – в группе сравнения 2). Результаты. Демиелинизирующие изменения сегментарного моторного проведения оказались достоверно (p<0,05) более выражены в обеих группах сравнения при более агрессивном течении заболевания – в подгруппе пациентов с диабетической полинейропатией при нарастании балла по NDS и в подгруппе пациентов с боковым амиотрофическим склерозом при быстром темпе прогрессирования по шкале ALSFRS-R. У пациентов с преимущественным поражением надсегментарных проводников – с миелопатиями – однократное нейрофизиологическое обследование не позволило судить о дальнейшем течении заболевания. Заключение. Полученные данные демонстрируют важность учета состояния миелина при оценке динамики течения заболеваний центральной и периферической нервной системы.
Introduction. It is known that during Wallerian degeneration, regeneration of axons after injury, secondary demyelination, as well as speed and quality recovery after nerve fiber damage are different in the central and peripheral nervous system. Objective – comparative assessment of the severity of axonopathy and secondary demyelination in patients with myelopathy, and diseases of the peripheral nervous system. Methods. The study involved 115 patients with myelopathy of different genesis and the statute of limitations (main study group), 70 patients with diabetic peripheral sensorimotor polyneuropathy (comparison group 1) and 90 patients with amyotrophic lateral sclerosis (comparison group 2). Segmental (all groups) and suprasegmental (Group principal and comparisons 2) engine research conducted electroneuromyography methods and transcranial magnetic stimulation. The disease was assessed by the specialized quantitative scales with the follow-up 3 months after the initial evaluation (FIM – the main group, NDS – group comparison 1, ALSFRS-R – in the comparison group 2). Results for: change of segmental demyelinating motor conduction were significantly (p<0,05) were more pronounced in the two comparison groups with a more aggressive course of the disease – in a subgroup of patients with diabetic polyneuropathy with an increase in magnitude on the NDS, and in the subgroup of patients with amyotrophic lateral sclerosis with rapid progression rate on a scale ALSFRS-R. In patients with a primary lesion of segmental conductors – with myelopathy – a single neurophysiological examination is not allowed to judge the future course of the disease. Conclusion. The findings demonstrate the importance of considering the state of myelin in assessing the dynamics of the flow diseases of the central and peripheral nervous system.
Key words: axonopathy, demyelination, neuropathy, amyotrophic lateral sclerosis, myelopathy, central and peripheral nervous system.
1. Морозов И.Н., Млявых С.Г. Эпидемиология позвоночно-спиномозговой травмы (обзор). Мед. альманах. 2011; 4 (7): 157–9. / Morozov I.N., Mliavykh S.G. Epidemiologiia pozvonochno-spinomozgovoi travmy (obzor). Med. al'manakh. 2011; 4 (7): 157–9. [in Russian]
2. Миронов Е.М. Анализ первичной инвалидности среди больных с последствиями позвоночно-спинномозговой травмы. Медико-социальная экспертиза и реабилитация. 2004; 1: 33–4. / Mironov E.M. Analiz pervichnoi invalidnosti sredi bol'nykh s posledstviiami pozvonochno-spinnomozgovoi travmy. Mediko-sotsial'naia ekspertiza i reabilitatsiia. 2004; 1: 33–4. [in Russian]
3. Кондаков Е.Н., Симонова И.А., Поляков И.В. Эпидемиология тpавм позвоночника и спинного мозга в Санкт-Петеpбуpге. Вопр. нейрохирургии им. Н.Н.Бурденко. 2002; 2: 34. / Kondakov E.N., Simonova I.A., Poliakov I.V. Epidemiologiia tpavm pozvonochnika i spinnogo mozga v Sankt-Petepbupge. Vopr. neirokhirurgii im. N.N.Burdenko. 2002; 2: 34. [in Russian]
4. Иванова Г.Е., Крылов В.В., Цикунов М.Б. и др. Реабилитация больных с травматической болезнью спинного мозга. М., 2010. / Ivanova G.E., Krylov V.V., Tsikunov M.B. i dr. Reabilitatsiia bol'nykh s travmaticheskoi bolezn'iu spinnogo mozga. M., 2010. [in Russian]
5. Goldberg J, Barres B. The relationship between neuronal survival and regeneration. Annu Rev Neurosci 2000; 23: 579–612.
6. Stoll G, Jander S, Myers R. Degeneration and regeneration on the peripheral nervous system: from Augustus Waller’s observations to neuroinglammation. J Peripher Nevr Syst 2002; 7: 13–27.
7. Schwaiger F, Hager G, Schmitt A et al. Peripheral but not central axonotomy induces changes in Janus kinases (JAK) and signal transduces and activators of transcription (STAT). Eur J Neurosci 2000; 12: 1165–76.
8. Dusart L, Airaksinen M, Sotelo C. Purkinje cell survival and axonal regeneration are age dependent: an in vitro study. J Neurosci 1997; 17: 3710–26.
9. Gianola S, Rossi F. Evolution of the Purkije cell resronse to injuri and regenerative potential during postnatal development of the rat cerebellum. J Comp Neurol 2001; 430: 101–17.
10. Steeves J, Keirstead H, Ethell D et al. Permissive and restrictive periods for brainstem-spinal regeneration in the chick. Prog Brain Res 1994; 103: 243–62.
11. Shamash S, Reichert F, Rotshenker S. The cytokine network of Wallerian degeneration: tumor necrosis facror-alpha, interleukin-1alpha and interleukin-1beta. J Neurosci 2002; 22: 3052–60.
12. Stoll G, Jander S. The role of microglia and macrophages in the pathophysiology of the CNS. Prog Neurobiol 1999; 58: 233–47.
13. George R, Griffin J. Delayed macrophage responses and myelin clearance during Wallerian degeneration in the central neurous system: the dorsal radiculotomi model. Exp Neurol 1994; 129: 225–36.
14. Caroni P, Schwab M. Two membrane protein fractions from rat central myelin with ingiitory properties for neurite growth and fibroblast spreading. J Cell Biol 1988; 106: 1281–8.
15. Bandlow C, Zachleder T, Schwab M. Oligodendrocytes arrest neurite grown by contact ingibition. J Neurosci 1990; 10: 3837–48.
16. Kalil K, Reh T. A light and electron microscopic study of regrowing pyramidal tract fibers. J Comp Neurol 1982; 211: 265–75.
17. Saunders N, Kitchener P, Knott G et al. Development of walking, swimming and neuronal connections after complete spinal cord transection in neonatal opossum, Monodelphisdomestica. J Neurosci 1998; 18: 339–55.
18. Young W. Strategies for the development of new and better farmacogical treatment for acute spinal cord injury. In: F.G.Seil. Advances in neurology. New York: Raven Press, 1993; p. 249–56.
19. Mori N, Morii H. SCGIO-related neuronal growth-associated proteins in neural development, plasticity, degeneration and aging. J Neurosci Res 2002; 70: 264–73.
20. Bouslama-Oueghlani L, Wehrle R, Sotelo C, Dusart I. The developmental loss of the ability of Purkinje cells to regenerate their axons occurs in the absence of myelin: an in vitro model to prevent myelination. J Neurosci 2003; 23: 8318–29.
21. Colemann M, Perry V. Axon pathology in neurological disease: a neglected therapeutic target. Trends Neurocsci 2002; 25: 532–7.
22. Baldwin K, Giger R. Insights into the physiological role of CNS regeneration inhibitors. Front Mol Neurosci 2015; 11 (8): 23.
23. Barbay S, Plautz E, Zoubina et al. Effects of postinfarct myelin-associated glycoprotein antibody treatment on motor recovery and motor map plasticity in squirrel monkeys. Stroke 2015; 46 (6): 1620–5.
24. Goldshmit Y, Frisca F, Kaslin J et al. Decreased anti-regenerative effects after spinal cord injury in spry4-/- mice. Neuroscience 2015; 287C: 104–12.
25. Kubo T, Yamaguchi A, Iwata N, Yamashita T The therapeutic effects of Rho-ROCK inhibitors on CNS disorders. Ther Clin Risk Manag 2008; 4 (3): 605–15.
26. Tönges L, Günthe R, Surh M et al. Rho kinase inhibition modulates microglia activation and improves survival in a model of amyotrophic lateral sclerosis. Glia 2014; 62 (2): 217–32.
27. Sreedharan J, Neukomm L, Brown R, Freeman M. Age-Dependent TDP-43-Mediated Motor Neuron Degeneration Requires GSK3, hat-trick, and xmas-2. Curr Biol 2015 17; 25 (16): 2130–6.
28. Ковражкина Е.А., Стаховская Л.В., Разинская О.Д. Динамика нейрофизиологических показателей сегментарного и надсегментарного моторного проведения у пациентов с миелопатиями и церебральным инсультом. Consilium Medicum. 2016; 18 (2): 118–24. / Kovrazhkina E.A., Stahovskaya L.V., Razinskaya O.D. The dynamics of neurophysiological signs of segmental and suprasegmental motor conduction at patients with myelopathy and cerebral stroke. Consilium Medicum. 2016; 18 (2): 118–24. [in Russian]
29. Ковражкина Е.А. Демиелинизирующие формы полинейропатий у пациентов с сахарным диабетом и хронической алкогольной интоксикацией. Журн. неврологии и психиатрии им. С.С.Корсакова. 2012; 5: 41–5. / Kovrazhkina E.A. Demieliniziruiushchie formy polineiropatii u patsientov s sakharnym diabetom i khronicheskoi alkogol'noi intoksikatsiei. Zhurn. nevrologii i psikhiatrii im. S.S.Korsakova. 2012; 5: 41–5. [in Russian]
30. Ковражкина Е.А. Аксональные полинейропатии: патогенез и лечение. Журн. неврологии и психиатрии им. С.С.Корсакова. 2013; 6: 22–5. / Kovrazhkina E.A. Aksonal'nye polineiropatii: patogenez i lechenie. Zhurn. nevrologii i psikhiatrii im. S.S.Korsakova. 2013; 6: 22–5. [in Russian]
31. Niemi J, DeFrancesco-Lisowitz A, Roldán-Hernández L et al. A critical role for macrophages near axotomized neuronal cell bodies in stimulating nerve regeneration.
J Neurosci 2013; 33 (41): 16236–48.
32. Marinelli S, Nazio F, Tinariet A et al. Schwann cell autophagy counteracts the onset and chronification of neuropathic pain. Pain 2014; 155 (1): 93–107.
33. DeFrancesco-Lisowitz A, Lindborg J, Niemi J, Zigmond R. The neuroimmunology of degeneration and regeneration in the peripheral nervous system. Neuroscience 2015; 302: 174–203.
34. Mar F, Da Silva T, Morgado M t al. Myelin Lipids Inhibit Axon Regeneration Following Spinal Cord Injury: a Novel Perspective for Therapy. Mol Neurobiol 2016; 53 (2): 1052–64.
35. Armstrong R, Mierzwa A, Marion C, Sullivan G. White matter involvement after TBI: Clues to axon and myelin repair capacity. Exp Neurol 2016; 275 (Pt. 3): 328–33.
36. Fujita Y, Yamashita T. Axon growth inhibition by RhoA/ROCK in the central nervous system. Front Neurosci 2014; 8: 338.
________________________________________________
1. Morozov I.N., Mliavykh S.G. Epidemiologiia pozvonochno-spinomozgovoi travmy (obzor). Med. al'manakh. 2011; 4 (7): 157–9. [in Russian]
2. Mironov E.M. Analiz pervichnoi invalidnosti sredi bol'nykh s posledstviiami pozvonochno-spinnomozgovoi travmy. Mediko-sotsial'naia ekspertiza i reabilitatsiia. 2004; 1: 33–4. [in Russian]
3. Kondakov E.N., Simonova I.A., Poliakov I.V. Epidemiologiia tpavm pozvonochnika i spinnogo mozga v Sankt-Petepbupge. Vopr. neirokhirurgii im. N.N.Burdenko. 2002; 2: 34. [in Russian]
4. Ivanova G.E., Krylov V.V., Tsikunov M.B. i dr. Reabilitatsiia bol'nykh s travmaticheskoi bolezn'iu spinnogo mozga. M., 2010. [in Russian]
5. Goldberg J, Barres B. The relationship between neuronal survival and regeneration. Annu Rev Neurosci 2000; 23: 579–612.
6. Stoll G, Jander S, Myers R. Degeneration and regeneration on the peripheral nervous system: from Augustus Waller’s observations to neuroinglammation. J Peripher Nevr Syst 2002; 7: 13–27.
7. Schwaiger F, Hager G, Schmitt A et al. Peripheral but not central axonotomy induces changes in Janus kinases (JAK) and signal transduces and activators of transcription (STAT). Eur J Neurosci 2000; 12: 1165–76.
8. Dusart L, Airaksinen M, Sotelo C. Purkinje cell survival and axonal regeneration are age dependent: an in vitro study. J Neurosci 1997; 17: 3710–26.
9. Gianola S, Rossi F. Evolution of the Purkije cell resronse to injuri and regenerative potential during postnatal development of the rat cerebellum. J Comp Neurol 2001; 430: 101–17.
10. Steeves J, Keirstead H, Ethell D et al. Permissive and restrictive periods for brainstem-spinal regeneration in the chick. Prog Brain Res 1994; 103: 243–62.
11. Shamash S, Reichert F, Rotshenker S. The cytokine network of Wallerian degeneration: tumor necrosis facror-alpha, interleukin-1alpha and interleukin-1beta. J Neurosci 2002; 22: 3052–60.
12. Stoll G, Jander S. The role of microglia and macrophages in the pathophysiology of the CNS. Prog Neurobiol 1999; 58: 233–47.
13. George R, Griffin J. Delayed macrophage responses and myelin clearance during Wallerian degeneration in the central neurous system: the dorsal radiculotomi model. Exp Neurol 1994; 129: 225–36.
14. Caroni P, Schwab M. Two membrane protein fractions from rat central myelin with ingiitory properties for neurite growth and fibroblast spreading. J Cell Biol 1988; 106: 1281–8.
15. Bandlow C, Zachleder T, Schwab M. Oligodendrocytes arrest neurite grown by contact ingibition. J Neurosci 1990; 10: 3837–48.
16. Kalil K, Reh T. A light and electron microscopic study of regrowing pyramidal tract fibers. J Comp Neurol 1982; 211: 265–75.
17. Saunders N, Kitchener P, Knott G et al. Development of walking, swimming and neuronal connections after complete spinal cord transection in neonatal opossum, Monodelphisdomestica. J Neurosci 1998; 18: 339–55.
18. Young W. Strategies for the development of new and better farmacogical treatment for acute spinal cord injury. In: F.G.Seil. Advances in neurology. New York: Raven Press, 1993; p. 249–56.
19. Mori N, Morii H. SCGIO-related neuronal growth-associated proteins in neural development, plasticity, degeneration and aging. J Neurosci Res 2002; 70: 264–73.
20. Bouslama-Oueghlani L, Wehrle R, Sotelo C, Dusart I. The developmental loss of the ability of Purkinje cells to regenerate their axons occurs in the absence of myelin: an in vitro model to prevent myelination. J Neurosci 2003; 23: 8318–29.
21. Colemann M, Perry V. Axon pathology in neurological disease: a neglected therapeutic target. Trends Neurocsci 2002; 25: 532–7.
22. Baldwin K, Giger R. Insights into the physiological role of CNS regeneration inhibitors. Front Mol Neurosci 2015; 11 (8): 23.
23. Barbay S, Plautz E, Zoubina et al. Effects of postinfarct myelin-associated glycoprotein antibody treatment on motor recovery and motor map plasticity in squirrel monkeys. Stroke 2015; 46 (6): 1620–5.
24. Goldshmit Y, Frisca F, Kaslin J et al. Decreased anti-regenerative effects after spinal cord injury in spry4-/- mice. Neuroscience 2015; 287C: 104–12.
25. Kubo T, Yamaguchi A, Iwata N, Yamashita T The therapeutic effects of Rho-ROCK inhibitors on CNS disorders. Ther Clin Risk Manag 2008; 4 (3): 605–15.
26. Tönges L, Günthe R, Surh M et al. Rho kinase inhibition modulates microglia activation and improves survival in a model of amyotrophic lateral sclerosis. Glia 2014; 62 (2): 217–32.
27. Sreedharan J, Neukomm L, Brown R, Freeman M. Age-Dependent TDP-43-Mediated Motor Neuron Degeneration Requires GSK3, hat-trick, and xmas-2. Curr Biol 2015 17; 25 (16): 2130–6.
28. Kovrazhkina E.A., Stahovskaya L.V., Razinskaya O.D. The dynamics of neurophysiological signs of segmental and suprasegmental motor conduction at patients with myelopathy and cerebral stroke. Consilium Medicum. 2016; 18 (2): 118–24. [in Russian]
29. Kovrazhkina E.A. Demieliniziruiushchie formy polineiropatii u patsientov s sakharnym diabetom i khronicheskoi alkogol'noi intoksikatsiei. Zhurn. nevrologii i psikhiatrii im. S.S.Korsakova. 2012; 5: 41–5. [in Russian]
30. Kovrazhkina E.A. Aksonal'nye polineiropatii: patogenez i lechenie. Zhurn. nevrologii i psikhiatrii im. S.S.Korsakova. 2013; 6: 22–5. [in Russian]
31. Niemi J, DeFrancesco-Lisowitz A, Roldán-Hernández L et al. A critical role for macrophages near axotomized neuronal cell bodies in stimulating nerve regeneration.
J Neurosci 2013; 33 (41): 16236–48.
32. Marinelli S, Nazio F, Tinariet A et al. Schwann cell autophagy counteracts the onset and chronification of neuropathic pain. Pain 2014; 155 (1): 93–107.
33. DeFrancesco-Lisowitz A, Lindborg J, Niemi J, Zigmond R. The neuroimmunology of degeneration and regeneration in the peripheral nervous system. Neuroscience 2015; 302: 174–203.
34. Mar F, Da Silva T, Morgado M t al. Myelin Lipids Inhibit Axon Regeneration Following Spinal Cord Injury: a Novel Perspective for Therapy. Mol Neurobiol 2016; 53 (2): 1052–64.
35. Armstrong R, Mierzwa A, Marion C, Sullivan G. White matter involvement after TBI: Clues to axon and myelin repair capacity. Exp Neurol 2016; 275 (Pt. 3): 328–33.
36. Fujita Y, Yamashita T. Axon growth inhibition by RhoA/ROCK in the central nervous system. Front Neurosci 2014; 8: 338.
Авторы
Е.А.Ковражкина*, Л.В.Стаховская, О.Д.Разинская
ФГБОУ ВО Российский национальный исследовательский медицинский университет им. Н.И.Пирогова Минздрава России. 117997, Россия, Москва, ул. Островитянова, д. 1
*elekov2@yandex.ru
________________________________________________
E.A.Kovrazhkina*, L.V.Stahovskaya, O.D.Razinskaya
N.I.Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation. 117997, Russian Federation, Moscow, ul. Ostrovitianova, d. 1
*elekov2@yandex.ru