Advertisement

Experimental Laceration Spinal Cord Injury Model in Rodents

  • Yi Ping Zhang
  • Lisa B. E. ShieldsEmail author
  • Christopher B. Shields
Chapter
Part of the Springer Series in Translational Stroke Research book series (SSTSR)

Abstract

Experimental laceration spinal cord injury (l-SCI) is an important in vivo model to investigate mechanisms of axonal regeneration and neurite plasticity following SCI. l-SCI is customarily performed freehand under visual guidance that results in variable lesion depths and shapes. In this chapter, a precise l- SCI model will be described for rodents using the Louisville Injury System Apparatus (LISA). This method incorporates: (1) reliable vertebral stabilization and spinal cord exposure and (2) accurate tissue laceration without contusion.

Keywords

Spinal cord injury Laceration SCI model Louisville Injury System Apparatus (LISA) Axonal regeneration 

Notes

Acknowledgment

We acknowledge Norton Healthcare for their continued support.

References

  1. 1.
    Bunge RP, Puckett WR, Becerra JL, Marcillo A, Quencer RM. Observations on the pathology of human spinal cord injury. A review and classification of 22 new cases with details from a case of chronic cord compression with extensive focal demyelination. Adv Neurol. 1993;59:75–89.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Quencer RM, Bunge RP. The injured spinal cord: imaging, histopathologic clinical correlates, and basic science approaches to enhancing neural function after spinal cord injury. Spine (Phila Pa 1976). 1996;21:2064–6.CrossRefGoogle Scholar
  3. 3.
    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;26:1–15.CrossRefGoogle Scholar
  4. 4.
    Sherry BA, Alava G, Tracey KJ, Martiney J, Cerami A, Slater AF. Malaria-specific metabolite hemozoin mediates the release of several potent endogenous pyrogens (TNF, MIP-1 alpha, and MIP-1 beta) in vitro, and altered thermoregulation in vivo. J Inflamm. 1995;45:85–96.PubMedGoogle Scholar
  5. 5.
    Bradbury EJ, Moon LD, Popat RJ, King VR, Bennett GS, Patel PN, Fawcett JW, McMahon SB. Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature. 2002;416:636–40.CrossRefGoogle Scholar
  6. 6.
    Silver J, Schwab ME, Popovich PG. Central nervous system regenerative failure: role of oligodendrocytes, astrocytes, and microglia. Cold Spring Harb Perspect Biol. 2015;7:a020602.CrossRefGoogle Scholar
  7. 7.
    Chen MS, Huber AB, van der Haar ME, Frank M, Schnell L, Spillmann AA, Christ F, Schwab ME. Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1. Nature. 2000;403:434–9.CrossRefGoogle Scholar
  8. 8.
    Fournier AE, Gould GC, Liu BP, Strittmatter SM. Truncated soluble Nogo receptor binds Nogo-66 and blocks inhibition of axon growth by myelin. J Neurosci. 2002;22:8876–83.CrossRefGoogle Scholar
  9. 9.
    Kim JE, Liu BP, Park JH, Strittmatter SM. Nogo-66 receptor prevents raphespinal and rubrospinal axon regeneration and limits functional recovery from spinal cord injury. Neuron. 2004;44:439–51.CrossRefGoogle Scholar
  10. 10.
    Pasterkamp RJ, Verhaagen J. Emerging roles for semaphorins in neural regeneration. Brain Res Brain Res Rev. 2001;35:36–54.CrossRefGoogle Scholar
  11. 11.
    Figueroa JD, Benton RL, Velazquez I, Torrado AI, Ortiz CM, Hernandez CM, Diaz JJ, Magnuson DS, Whittemore SR, Miranda JD. Inhibition of EphA7 up-regulation after spinal cord injury reduces apoptosis and promotes locomotor recovery. J Neurosci Res. 2006;84:1438–51.CrossRefGoogle Scholar
  12. 12.
    Kempf A, Montani L, Petrinovic MM, Schroeter A, Weinmann O, Patrignani A, Schwab ME. Upregulation of axon guidance molecules in the adult central nervous system of Nogo-A knockout mice restricts neuronal growth and regeneration. Eur J Neurosci. 2013;38:3567–79.CrossRefGoogle Scholar
  13. 13.
    Ramer MS, Harper GP, Bradbury EJ. Progress in spinal cord research—a refined strategy for the International Spinal Research Trust. Spinal Cord. 2000;38:449–72.CrossRefGoogle Scholar
  14. 14.
    Inman D, Guth L, Steward O. Genetic influences on secondary degeneration and wound healing following spinal cord injury in various strains of mice. J Comp Neurol. 2002;451:225–35.CrossRefGoogle Scholar
  15. 15.
    Steward O, Schauwecker PE, Guth L, Zhang Z, Fujiki M, Inman D, Wrathall J, Kempermann G, Gage FH, Saatman KE, Raghupathi R, McIntosh T. Genetic approaches to neurotrauma research: opportunities and potential pitfalls of murine models. Exp Neurol. 1999;157:19–42.CrossRefGoogle Scholar
  16. 16.
    Kim JE, Li S, GrandPre T, Qiu D, Strittmatter SM. Axon regeneration in young adult mice lacking Nogo-A/B. Neuron. 2003;38:187–99.CrossRefGoogle Scholar
  17. 17.
    Simonen M, Pedersen V, Weinmann O, Schnell L, Buss A, Ledermann B, Christ F, Sansig G, van der Putten H, Schwab ME. Systemic deletion of the myelin-associated outgrowth inhibitor Nogo-A improves regenerative and plastic responses after spinal cord injury. Neuron. 2003;38:201–11.CrossRefGoogle Scholar
  18. 18.
    Zheng B, Ho C, Li S, Keirstead H, Steward O, Tessier-Lavigne M. Lack of enhanced spinal regeneration in Nogo-deficient mice. Neuron. 2003;38:213–24.CrossRefGoogle Scholar
  19. 19.
    Frisen J, Fried K, Sjogren AM, Risling M. Growth of ascending spinal axons in CNS scar tissue. Int J Dev Neurosci. 1993;11:461–75.CrossRefGoogle Scholar
  20. 20.
    Hermanns S, Reiprich P, Muller HW. A reliable method to reduce collagen scar formation in the lesioned rat spinal cord. J Neurosci Methods. 2001;110:141–6.CrossRefGoogle Scholar
  21. 21.
    Seitz A, Aglow E, Heber-Katz E. Recovery from spinal cord injury: a new transection model in the C57Bl/6 mouse. J Neurosci Res. 2002;67:337–45.CrossRefGoogle Scholar
  22. 22.
    Iannotti C, Zhang YP, Shields LBE, Han Y, Burke DA, Xu XM, Shields CB. Dural repair reduces connective tissue scar invasion and cystic cavity formation after acute spinal cord laceration injury in adult rats. J Neurotrauma. 2006;23:853–65.CrossRefGoogle Scholar
  23. 23.
    Zhang YP, Iannotti C, Shields LBE, Han Y, Burke DA, Xu XM, Shields CB. Dural closure, cord approximation, and clot removal: enhancement of tissue sparing in a novel laceration spinal cord injury model. J Neurosurg. 2004;100:343–52.Google Scholar
  24. 24.
    Onifer SM, Zhang YP, Burke DA, Brooks DL, Decker JA, McClure NJ, Floyd AR, Hall J, Proffitt BL, Shields CB, Magnuson DS. Adult rat forelimb dysfunction after dorsal cervical spinal cord injury. Exp Neurol. 2005;192:25–38.CrossRefGoogle Scholar
  25. 25.
    Zhang YP, Walker MJ, Shields LBE, Wang X, Walker CL, Xu XM, Shields CB. Controlled cervical laceration injury in mice. J Vis Exp. 2013:50030.Google Scholar
  26. 26.
    Yu P, Zhang YP, Shields LBE, Zheng Y, Hu X, Hill R, Howard R, Gu Z, Burke DA, Whittemore SR, Xu XM, Shields CB. Inhibitor of DNA binding 2 promotes sensory axonal growth after SCI. Exp Neurol. 2011;231:38–44.CrossRefGoogle Scholar
  27. 27.
    Sivasankaran R, Pei J, Wang KC, Zhang YP, Shields CB, Xu XM, He Z. PKC mediates inhibitory effects of myelin and chondroitin sulfate proteoglycans on axonal regeneration. Nat Neurosci. 2004;7:261–8.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Yi Ping Zhang
    • 1
  • Lisa B. E. Shields
    • 1
    Email author
  • Christopher B. Shields
    • 1
    • 2
  1. 1.Norton Neuroscience Institute, Norton HealthcareLouisvilleUSA
  2. 2.Department of Anatomical Sciences and NeurobiologyUniversity of Louisville School of MedicineLouisvilleUSA

Personalised recommendations