Skip to main content
SpringerLink
Log in
Book cover

Animal Models of Acute Neurological Injury pp 499–512Cite as

Rodent Spinal Cord Demyelination Models

  • Chapter
  • First Online:

  • 645 Accesses

Part of the book series: Springer Series in Translational Stroke Research ((SSTSR))

Abstract

Oligodendrocyte loss and subsequent demyelination is a significant component of the demyelinating diseases such as multiple sclerosis (MS) and traumatic CNS injury such as spinal cord (SCI) or traumatic brain (TBI) injury. Therefore, remyelination, either by enhancing endogenous myelination or engrafting exogenous myelinating cells, is a viable therapeutic target to restore function. To assess specific approaches to facilitate functional remyelination in vivo, appropriate injury models are needed. This chapter will discuss the strengths and weaknesses of a number of demyelinating lesions of the spinal cord and provide guidelines for choosing which model best suits which experimental condition. Step by step procedures for both creating and assessing the lesion will be provided.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Woodruff RH, Franklin RJ. Demyelination and remyelination of the caudal cerebellar peduncle of adult rats following stereotaxic injections of lysolecithin, ethidium bromide, and complement/anti-galactocerebroside: a comparative study. Glia. 1999;25:216–28.

    Article  CAS  Google Scholar 

  2. Matsushima GK, Morell P. The neurotoxicant, cuprizone, as a model to study demyelination and remyelination in the central nervous system. Brain Pathol. 2001;11:107–16.

    Article  CAS  Google Scholar 

  3. Herder V, Hansmann F, Stangel M, Skripuletz T, Baumgartner W, Beineke A. Lack of cuprizone-induced demyelination in the murine spinal cord despite oligodendroglial alterations substantiates the concept of site-specific susceptibilities of the central nervous system. Neuropathol Appl Neurobiol. 2011;37:676–84.

    Article  CAS  Google Scholar 

  4. Blakemore WF. The response of oligodendrocytes to chemical injury. Acta Neurol Scand Suppl. 1984;100:33–8.

    CAS  PubMed  Google Scholar 

  5. Blakemore WF. Ethidium bromide induced demyelination in the spinal cord of the cat. Neuropathol Appl Neurobiol. 1982;8:365–75.

    Article  CAS  Google Scholar 

  6. Desjardins P, Frost E, Morais R. Ethidium bromide-induced loss of mitochondrial DNA from primary chicken embryo fibroblasts. Mol Cell Biol. 1985;5:1163–9.

    Article  CAS  Google Scholar 

  7. Hayakawa T, Noda M, Yasuda K, Yorifuji H, Taniguchi S, Miwa I, Sakura H, Terauchi Y, Hayashi J, Sharp GW, Kanazawa Y, Akanuma Y, Yazaki Y, Kadowaki T. Ethidium bromide-induced inhibition of mitochondrial gene transcription suppresses glucose-stimulated insulin release in the mouse pancreatic beta-cell line betaHC9. J Biol Chem. 1998;273:20300–7.

    Article  CAS  Google Scholar 

  8. Hayashi J, Tanaka M, Sato W, Ozawa T, Yonekawa H, Kagawa Y, Ohta S. Effects of ethidium bromide treatment of mouse cells on expression and assembly of nuclear-coded subunits of complexes involved in the oxidative phosphorylation. Biochem Biophys Res Commun. 1990;167:216–21.

    Article  CAS  Google Scholar 

  9. Kuypers NJ, James KT, Enzmann GU, Magnuson DS, Whittemore SR. Functional consequences of ethidium bromide demyelination of the mouse ventral spinal cord. Exp Neurol. 2013;247:615–22.

    Article  CAS  Google Scholar 

  10. Crang AJ, Blakemore WF. Remyelination of demyelinated rat axons by transplanted mouse oligodendrocytes. Glia. 1991;4:305–13.

    Article  CAS  Google Scholar 

  11. Penderis J, Shields SA, Franklin RJ. Impaired remyelination and depletion of oligodendrocyte progenitors does not occur following repeated episodes of focal demyelination in the rat central nervous system. Brain. 2003;126(Pt 6):1382–91.

    Article  Google Scholar 

  12. Graca DL, Blakemore WF. Delayed remyelination in rat spinal cord following ethidium bromide injection. Neuropathol Appl Neurobiol. 1986;12(6):593–605.

    Article  CAS  Google Scholar 

  13. Talbott JF, Loy DN, Liu Y, Qiu MS, Bunge MB, Rao MS, Whittemore SR. Endogenous Nkx2.2+/Olig2+ oligodendrocyte precursor cells fail to remyelinate the demyelinated spinal cord in the absence of astrocytes. Exp Neurol. 2005;192:11–24.

    Article  CAS  Google Scholar 

  14. Talbott JF, Cao Q, Achim V, Benton RL, Enzmann GU, Mills MD, Rao MS, Whittemore SR. Schwann cell differentiation of adult oligodendrocyte precursor cells engrafted into the demyelinated spinal cord is BMP-dependent. Glia. 2006;54:147–59.

    Article  Google Scholar 

  15. Miron VE, Franklin RJ. Macrophages and CNS remyelination. J Neurochem. 2014;130:165–71.

    Article  CAS  Google Scholar 

  16. Arnett HA, Fancy SP, Alberta JA, Zhao C, Plant SR, Kaing S, Raine CS, Rowitch DH, Franklin RJ, Stiles CD. bHLH transcription factor Olig1 is required to repair demyelinated lesions in the CNS. Science. 2004;306:2111–5.

    Article  CAS  Google Scholar 

  17. Blakemore WF, Franklin RJ. Remyelination in experimental models of toxin-induced demyelination. Curr Top Microbiol Immunol. 2008;318:193–212.

    CAS  PubMed  Google Scholar 

  18. McKay JS, Blakemore WF, Franklin RJ. Trapidil-mediated inhibition of CNS remyelination results from reduced numbers and impaired differentiation of oligodendrocytes. Neuropathol Appl Neurobiol. 1998;24:498–506.

    Article  CAS  Google Scholar 

  19. Zhu Q, Whittemore SR, Devries WH, Zhao X, Kuypers NJ, Qiu M. Dorsally-derived oligodendrocytes in the spinal cord contribute to axonal myelination during development and remyelination following focal demyelination. Glia. 2011;59:1612–21.

    Article  Google Scholar 

  20. Keirstead HS, Blakemore WF. Identification of post-mitotic oligodendrocytes incapable of remyelination within the demyelinated adult spinal cord. J Neuropathol Exp Neurol. 1997;56:1191–201.

    Article  CAS  Google Scholar 

  21. Kuypers NJ, Bankston AN, Howard RM, Beare JE, Whittemore SR. Remyelinating oligodendrocyte precursor cell miRNAs from the Sfmbt2 cluster promote cell cycle arrest and differentiation. J Neurosci. 2016;36:1698–710.

    Article  CAS  Google Scholar 

  22. Walshe JM. Copper: not too little, not too much, but just right. J R Coll Physicians Lond. 1995;29:280–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Kipp M, Clarner T, Dang J, Copray S, Beyer C. The cuprizone animal model: new insights into an old story. Acta Neuropathol. 2009;118:723–36.

    Article  Google Scholar 

  24. Morell P, Barrett CV, Mason JL, Toews AD, Hostettler JD, Knapp GW, Matsushima GK. Gene expression in brain during cuprizone-induced demyelination and remyelination. Mol Cell Neurosci. 1998;12:220–7.

    Article  CAS  Google Scholar 

  25. Jurevics H, Hostettler J, Muse ED, Sammond DW, Matsushima GK, Toews AD, Morell P. Cerebroside synthesis as a measure of the rate of remyelination following cuprizone-induced demyelination in brain. J Neurochem. 2001;77:1067–76.

    Article  CAS  Google Scholar 

  26. Tsunoda I, Fujinami RS. Two models for multiple sclerosis: experimental allergic encephalomyelitis and Theiler’s murine encephalomyelitis virus. J Neuropathol Exp Neurol. 1996;55:673–86.

    Article  CAS  Google Scholar 

  27. Zamvil SS, Steinman L. The T lymphocyte in experimental allergic encephalomyelitis. Annu Rev Immunol. 1990;8:579–621.

    Article  CAS  Google Scholar 

  28. Kuchroo VK, Anderson AC, Waldner H, Munder M, Bettelli E, Nicholson LB. T cell response in experimental autoimmune encephalomyelitis (EAE): role of self and cross-reactive antigens in shaping, tuning, and regulating the autopathogenic T cell repertoire. Annu Rev Immunol. 2002;20:101–23.

    Article  CAS  Google Scholar 

  29. Alley J, Khasabov S, Simone D, Beitz A, Rodriguez M, Njenga MK. More severe neurologic deficits in SJL/J male than female mice following Theiler’s virus-induced CNS demyelination. Exp Neurol. 2003;180:14–24.

    Article  Google Scholar 

  30. Constantinescu CS, Farooqi N, O’Brien K, Gran B. Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). Br J Pharmacol. 2011;164:1079–106.

    Article  CAS  Google Scholar 

  31. Robinson AP, Harp CT, Noronha A, Miller SD. The experimental autoimmune encephalomyelitis (EAE) model of MS: utility for understanding disease pathophysiology and treatment. Handb Clin Neurol. 2014;122:173–89.

    Article  Google Scholar 

  32. Mecha M, Carrillo-Salinas FJ, Mestre L, Feliu A, Guaza C. Viral models of multiple sclerosis: neurodegeneration and demyelination in mice infected with Theiler’s virus. Prog Neurobiol. 2013;101–102:46–64.

    Article  Google Scholar 

  33. Franklin KBJ, Paxinos G. The mouse brain in stererotaxic coordinates. San Diego: Academic Press; 1997.

    Google Scholar 

  34. Paxinos G, Watson C. The rat brain in stereotaxic coordinates. San Diego: Academic; 1998.

    Google Scholar 

  35. Loy DN, Talbott JF, Onifer SM, Mills MD, Burke DA, Fajardo LC, Dennison JB, Magnuson DSK, Whittemore SR. Both dorsal and ventral spinal cord pathways contribute to overground locomotion in the adult rat. Exp Neurol. 2002;177:575–80.

    Article  Google Scholar 

  36. Loy DN, Magnuson DS, Zhang YP, Onifer SM, Mills MD, Cao QL, Darnall JB, Fajardo LC, Burke DA, Whittemore SR. Functional redundancy of ventral spinal locomotor pathways. J Neurosci. 2002;22:315–23.

    Article  CAS  Google Scholar 

  37. Hill RL, Zhang YP, Burke DA, Devries WH, Zhang Y, Magnuson DS, Whittemore SR, Shields CB. Anatomical and functional outcomes following a precise, graded, dorsal laceration spinal cord injury in C57BL/6 mice. J Neurotrauma. 2009;26(1):1–15.

    Article  Google Scholar 

  38. Beaumont E, Onifer SM, Reed WR, Magnuson DS. Magnetically evoked inter-enlargement response: an assessment of ascending propriospinal fibers following spinal cord injury. Exp Neurol. 2006;201:428–40.

    Article  Google Scholar 

Download references

Acknowledgements

Supported by RR15576/GM103507, NS054708, Norton Healthcare, Commonwealth of Kentucky Challenge for Excellence, and the Kentucky Spinal Cord and Head Injury Research Trust.

Author information

Author notes

  1. Nicholas J. Kuypers

    Present address: Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, KY, USA

Authors and Affiliations

  1. Kentucky Spinal Cord Injury Research Center, University of Louisville School of Medicine, Louisville, KY, USA

    Kariena R. Andres, Johnny R. Morehouse, Rachel Cary, Christine D. Yarberry, Nicholas J. Kuypers & Scott R. Whittemore

  2. Department of Neurological Surgery, University of Louisville School of Medicine, Louisville, KY, USA

    Kariena R. Andres, Johnny R. Morehouse, Rachel Cary, Christine D. Yarberry, Nicholas J. Kuypers & Scott R. Whittemore

  3. Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, KY, USA

    Scott R. Whittemore

Authors
  1. Kariena R. Andres
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Johnny R. Morehouse
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rachel Cary
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christine D. Yarberry
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nicholas J. Kuypers
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Scott R. Whittemore
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Scott R. Whittemore .

Editor information

Editors and Affiliations

  1. Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Jun Chen

  2. Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA

    Zao C. Xu

  3. Indiana University School of Medicine, SNRI SCBIRG, Indianapolis, IN, USA

    Xiao Ming Xu

  4. Center for Neuroscience Research, Loma Linda University School of Medicine, Loma Linda, CA, USA

    John H. Zhang

Electronic Supplementary Material

(MP4 364282 kb)

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Andres, K.R., Morehouse, J.R., Cary, R., Yarberry, C.D., Kuypers, N.J., Whittemore, S.R. (2019). Rodent Spinal Cord Demyelination Models. In: Chen, J., Xu, Z., Xu, X., Zhang, J. (eds) Animal Models of Acute Neurological Injury. Springer Series in Translational Stroke Research. Springer, Cham. https://doi.org/10.1007/978-3-030-16082-1_36

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-16082-1_36

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-16080-7

  • Online ISBN: 978-3-030-16082-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation