Journal of Molecular Neuroscience

, Volume 48, Issue 1, pp 144–153 | Cite as

Electromagnetic Field Stimulation Potentiates Endogenous Myelin Repair by Recruiting Subventricular Neural Stem Cells in an Experimental Model of White Matter Demyelination

  • Mohammad Amin Sherafat
  • Motahareh Heibatollahi
  • Somayeh Mongabadi
  • Fatemeh Moradi
  • Mohammad JavanEmail author
  • Abolhassan Ahmadiani


Electromagnetic fields (EMFs) may affect the endogenous neural stem cells within the brain. The aim of this study was to assess the effects of EMFs on the process of toxin-induced demyelination and subsequent remyelination. Demyelination was induced using local injection of lysophosphatidylcholine within the corpus callosum of adult female Sprague–Dawley rats. EMFs (60 Hz; 0.7 mT) were applied for 2 h twice a day for 7, 14, or 28 days postlesion. BrdU labeling and immunostaining against nestin, myelin basic protein (MBP), and BrdU were used for assessing the amount of neural stem cells within the tissue, remyelination patterns, and tracing of proliferating cells, respectively. EMFs significantly reduced the extent of demyelinated area and increased the level of MBP staining within the lesion area on days 14 and 28 postlesion. EMFs also increased the number of BrdU- and nestin-positive cells within the area between SVZ and lesion as observed on days 7 and 14 postlesion. It seems that EMF potentiates proliferation and migration of neural stem cells and enhances the repair of myelin in the context of demyelinating conditions.


Electromagnetic field stimulation Myelin repair Multiple sclerosis Lysophosphatidylcholine Endogenous neural stem cells Rat 



This study was supported by a grant from Neuroscience research center, Shahid Beheshti University of Medical Sciences, Tehran.


  1. Arendash GW, Sanchez-Ramos J et al (2010) Electromagnetic field treatment protects against and reverses cognitive impairment in Alzheimer’s disease mice. J Alzheim Dis 19(1):191–210Google Scholar
  2. Arias-Carrión O, Verdugo-DÃaz L et al (2004) Neurogenesis in the subventricular zone following transcranial magnetic field stimulation and nigrostriatal lesions. J Neurosci Res 78:16–28PubMedCrossRefGoogle Scholar
  3. Bistolfi F (2007) Extremely low-frequency pulsed magnetic fields and multiple sclerosis: effects on neurotransmission alone or also on immunomodulation? Building a working hypothesis. Neuroradiol J 20:676–693Google Scholar
  4. Calida DM, Constantinescu C et al (2001) Cutting edge: C3, a key component of complement activation, is not required for the development of myelin oligodendrocyte glycoprotein peptide-induced experimental autoimmune encephalomyelitis in mice. J Immunol 166:723–726PubMedGoogle Scholar
  5. Cantarella C, Cayre M et al (2008) Intranasal HB-EGF administration favors adult SVZ cell mobilization to demyelinated lesions in mouse corpus callosum. Dev Neurobiol 68:223–236PubMedCrossRefGoogle Scholar
  6. Caon C, Saunders C et al (2010) Injectable disease-modifying therapy for relapsing-remitting multiple sclerosis: a review of adherence data. J Neurosci Nurs 42(5):S5–S9PubMedCrossRefGoogle Scholar
  7. Cayre M, Bancila M et al (2006) Migrating and myelinating potential of subventricular zone neural progenitor cells in white matter tracts of the adult rodent brain. Mol Cell Neurosci 31:748–758PubMedCrossRefGoogle Scholar
  8. Cuccurazzu B, Leone L et al (2010) Exposure to extremely low-frequency (50 Hz) electromagnetic fields enhances adult hippocampal neurogenesis in C57BL/6 mice. Exp Neurol 226(1):173–182PubMedCrossRefGoogle Scholar
  9. Decker L, Picard-Riera N et al (2002) Growth factor treatment promotes mobilization of young but not aged adult subventricular zone precursors in response to demyelination. J Neurosci Res 69:763–771PubMedCrossRefGoogle Scholar
  10. Dubois-Dalcq M, French-Constant C et al (2005) Enhancing central nervous system remyelination in multiple sclerosis. Neuron 48:9–12PubMedCrossRefGoogle Scholar
  11. Ernst C, Christie BR (2005) Nestin-expressing cells and their relationship to mitotically active cells in the subventricular zones of the adult rat. Eur J Neurosci 22:3059–3066PubMedCrossRefGoogle Scholar
  12. Franklin R, Blakemore W (1997) To what extent is oligodendrocyte progenitor migration a limiting factor in the remyelination of multiple sclerosis lesions? Mul Scler 3:84–87CrossRefGoogle Scholar
  13. Funk RHW, Monsees TK (2006) Effects of electromagnetic fields on cells: physiological and therapeutical approaches and molecular mechanisms of interaction. Cells Tissues Organs 182:59–78PubMedCrossRefGoogle Scholar
  14. Gallo V, Armstrong R (2008) Myelin repair strategies: a cellular view. Curr Opin Neurol 21(3):278–283PubMedCrossRefGoogle Scholar
  15. Giacomini PS, Arnold DL et al (2009) Defining multiple sclerosis treatment response with magnetic resonance imaging. Arch Neurol 66(1):19–20PubMedCrossRefGoogle Scholar
  16. Goudarzvand M, Javan M et al (2010) Vitamins E and D3 attenuate demyelination and potentiate remyelination processes of hippocampal formation of rats following local Injection of ethidium bromide. Cell Mol Neurobiol 30:289–299PubMedCrossRefGoogle Scholar
  17. Griffiths I, Klugmann M et al (1998) Axonal swellings and degeneration in mice lacking the major proteolipid of myelin. Science 280:1610–1613PubMedCrossRefGoogle Scholar
  18. Hakansson N, Gustavsson P (2003) Neurodegenerative diseases in welders and other workers exposed to high levels of magnetic fields. Epidemiology 14:420–428PubMedGoogle Scholar
  19. Hernández-Hernández H, Cruces-Solis H et al (2009) Neurite outgrowth on chromaffin cells applying extremely low frequency magnetic fields by permanent magnets. Arch Med Res 40(7):545–550PubMedCrossRefGoogle Scholar
  20. Johansen C (2004) Electromagnetic fields and health effects - epidemiologic studies of cancer, diseases of the central nervous system and arrhythmia-related heart disease. Scand J Work Environ Health 30:1–30PubMedCrossRefGoogle Scholar
  21. Judit M, Stone TW (2007) New advances in the rehabilitation of CNS diseases applying rTMS. Expert Rev Neurother 7(2):165–177CrossRefGoogle Scholar
  22. Kerniea SG, Parent JM (2010) Forebrain neurogenesis after focal ischemic and traumatic brain injury. Neurobiol Dis 37(2):267–274CrossRefGoogle Scholar
  23. Kronenberg G, Reuter K et al (2003) Subpopulations of proliferating cells of the adult hippocampus respond differently to physiologic neurogenic stimuli. J Comp Neurol 467:455–463PubMedCrossRefGoogle Scholar
  24. Lappe-Siefke C, Goebbels S et al (2003) Disruption of Cnp1 uncouples oligodendroglial functions in axonal support and myelination. Nat Genet 33:366–374PubMedCrossRefGoogle Scholar
  25. Lappin M, Lawrie F et al (2003) Effects of a pulsed electromagnetic therapy on multiple sclerosis fatigue and quality of life: a double-blind, placebo controlled trial. Altern Ther Health Med 9(4):38–48PubMedGoogle Scholar
  26. Lendahl U, Zimmerman LB et al (1990) CNS stem cells express a new class of intermediate filament protein. Cell 60:585–595PubMedCrossRefGoogle Scholar
  27. Liburdy RP (1992) Calcium signaling in lymphocytes and ELF fields. Evidence for an electric field metric and a site of interaction involving the calcium ion channel. FEBS Lett 301:53–59PubMedCrossRefGoogle Scholar
  28. Mally J, Stone T (1999) Improvement in Parkinsonian symptoms after repetitive transcranial magnetic stimulation. J Neurol Sci 162:179–184PubMedCrossRefGoogle Scholar
  29. Markowitz C (2010) The current landscape and unmet needs in multiple sclerosis. Am J Manag Care 16(8):S211–S218PubMedGoogle Scholar
  30. Mason J, Toews A et al (2004) Oligodendrocytes and progenitors become progressively depleted with chronically demyelinated lesions. Am J Path 164:1673–1682PubMedCrossRefGoogle Scholar
  31. Miravalle A, Corboy JR (2010) Therapeutic options in multiple sclerosis. Neurology 75(18):S22–S27PubMedCrossRefGoogle Scholar
  32. Mozafari S, Sherafat MA et al (2010) Visual evoked potentials and MBP gene expression imply endogenous myelin repair in adult rat optic nerve and chiasm following local lysolecithin induced demyelination. Brain Res 1351:50–56PubMedCrossRefGoogle Scholar
  33. Mozafari S, Javan M et al (2011) Analysis of structural and molecular events associated with adult rat optic chiasm and nerves demyelination and remyelination; possible role for 3rd ventricle proliferating cells. NeuroMol Med 12:138–150CrossRefGoogle Scholar
  34. Nait-Oumesmar B, Picard-Riéra N et al (2008) The role of SVZderived neural precursors in demyelinating diseases: from animal models to multiple sclerosis. J Neurol Sci 268:26–31CrossRefGoogle Scholar
  35. Nave K-A, Trapp BD (2008) Axon-glial signaling and the glial support of axon function. Ann Rev Neurosci 31:535–561PubMedCrossRefGoogle Scholar
  36. Noseworthy JH, Lucchinetti C et al (2000) Multiple sclerosis. New Engl J Med 343:938–952PubMedCrossRefGoogle Scholar
  37. Papadopoulos D, Pham-Dinh D et al (2006) Axon loss is responsible for chronic neurological deficit following inflammatory demyelination in the rat. Exp Neurol 197:373–385PubMedCrossRefGoogle Scholar
  38. Pedro JAD, Pérez-Caballer AJ et al (2005) Pulsed electromagnetic fields induce peripheral nerve regeneration and endplate enzymatic changes. Bioelectromagnetics 26(1):20–27PubMedCrossRefGoogle Scholar
  39. Piacentini R, Ripoli C et al (2007) Extremely low-frequency electromagnetic fields promote in vitro neurogenesis via upregulation of Cav1-channel activity. J Cell Physiol 215(1):129–139CrossRefGoogle Scholar
  40. Piatkowski J, Kern S et al (2009) Effect of BEMER magnetic field therapy on the level of fatigue in patients with multiple sclerosis: a randomized, double-blind controlled trial. J Altern Complementary Med 15(5):507–511CrossRefGoogle Scholar
  41. Picard-Riera N, Decker L et al (2002) Experimental autoimmune encephalomyelitis mobilizes neural progenitors from the subventricular zone to undergo oligodendrogenesis in adult mice. Proc Natl Acad Sci U S A 99:13211–13216PubMedCrossRefGoogle Scholar
  42. Pluchino S, Martino G (2008) The therapeutic plasticity of neural stem/precursor cells in multiple sclerosis. J Neurol Sci 265(1):105–110PubMedCrossRefGoogle Scholar
  43. Popko B (2003) Myelin: not just a conduit for conduction. Nat Genet 33:327–328PubMedCrossRefGoogle Scholar
  44. Rajendra P, Sujatha H et al (2004) Biological effects of power frequency magnetic fields: neurochemical and toxicological changes in developing chick embryos. Biomagn Res Technol 2(1):1–9PubMedCrossRefGoogle Scholar
  45. Richards TL, Lappin MS et al (1997) Double-blind study of pulsing magnetic field effects on multiple sclerosis. J Altern Complementary Med 3(1):21–29CrossRefGoogle Scholar
  46. Sandyk R (1992) Successful treatment of multiple sclerosis with magnetic fields. Int J Neurosci Lett 66:237–250Google Scholar
  47. Sandyk R (1995) Premenstrual exacerbation of symptoms in multiple sclerosis is attenuated by treatment with weak electromagnetic fields. Int J Neurosci 83(3–4):187–198Google Scholar
  48. Sandyk R (1996) Treatment with weak electromagnetic fields improves fatigue associated with multiple sclerosis. Int J Neurosci 84:177–186PubMedCrossRefGoogle Scholar
  49. Sandyk R (1997) Immediate recovery of cognitive functions and resolution of fatigue by treatment with weak electromagnetic fields in a patient with multiple sclerosis. Int J Neurosci 90:59–74PubMedCrossRefGoogle Scholar
  50. Sandyk R, Dann LC (1994) Weak electromagnetic fields attenuate tremor in multiple sclerosis. Int J Neurosci 79(3–4):199–212PubMedCrossRefGoogle Scholar
  51. Sandyk R, Dann LC (1995) Resolution of Lhermitte’s sign in multiple sclerosis by treatment with weak electromagnetic fields. Int J Neurosci 81(1–2):215–224PubMedCrossRefGoogle Scholar
  52. Sandyk R, Lacono R (1994) Improvement by picoTesla range magnetic fields of perceptual-motor performance and visual memory in a patient with chronic progressive multiple sclerosis. Int J Neurosci Lett 78:53–66CrossRefGoogle Scholar
  53. Schlaier J, Eichhammer P et al (2007) Effects of spinal cord stimulation on cortical excitability in patients with chronic neuropathic pain: a pilot study. Eur J Pain 11:863–868PubMedCrossRefGoogle Scholar
  54. Seaberg RM, van der Kooy D (2002) Adult rodent neurogenic regions: the ventricular subependyma contains neural stem cells, but the dentate gyrus contains restricted progenitors. J Neurosci 22:1784–1793PubMedGoogle Scholar
  55. Sisken BF, Kanje M et al (1989) Stimulation of rat sciatic nerve regeneration with pulsed electromagnetic fields. Brain Res 485(2):309–316PubMedCrossRefGoogle Scholar
  56. Smith KJ, Blakemore WF et al (1979) Central remyelination restores secure conduction. Nature 280:395–396PubMedCrossRefGoogle Scholar
  57. Thomas P, Thomas S et al (2010) Multi-centre parallel arm randomised controlled trial to assess the effectiveness and cost-effectiveness of a group-based cognitive behavioural approach to managing fatigue in people with multiple sclerosis. BMC Neurol 16(10):43CrossRefGoogle Scholar
  58. Thompson A, Toosy A et al (2010) Pharmacological management of symptoms in multiple sclerosis: current approaches and future directions. Lancet Neurol 9(12):1182–1199PubMedCrossRefGoogle Scholar
  59. Walker JL, Kryscio R et al (2007) Electromagnetic field treatment of nerve crush injury in a rat model: effect of signal configuration on functional recovery. Bioelectromagnetics 28(4):256–263PubMedCrossRefGoogle Scholar
  60. Weintraub MI, Herrmann DN, Smith AG, Backonja MM, Cole SP (2009) Pulsed electromagnetic fields to reduce diabetic neuropathic pain and stimulate neuronal repair: a randomized controlled trial. Arch Phys Med Rehabil 90:1102–1109PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Mohammad Amin Sherafat
    • 1
  • Motahareh Heibatollahi
    • 1
  • Somayeh Mongabadi
    • 1
  • Fatemeh Moradi
    • 1
  • Mohammad Javan
    • 2
    Email author
  • Abolhassan Ahmadiani
    • 1
  1. 1.Neuroscience Research CenterShahid Beheshti University of Medical SciencesTehranIran
  2. 2.Department of Physiology, Faculty of Medical SciencesTarbiat Modares UniversityTehranIran

Personalised recommendations