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Summary

Abstract

Introduction

Protocol

Representative Results

Discussion

Acknowledgements

Materials

References

Medicine

A Contusion Model of Severe Spinal Cord Injury in Rats

Published: August 17th, 2013

DOI:

10.3791/50111

1Department of Neuroscience, Division of Neurosurgery, Medical University of South Carolina, 2Bioengineering, Clemson University, 3Clemson-MUSC Bioengineering Joint Program

A contusion model of severe spinal cord injury is described. Detailed pre-operative, operative and post-operative steps are described to obtain a consistent model.

The translational potential of novel treatments should be investigated in severe spinal cord injury (SCI) contusion models. A detailed methodology is described to obtain a consistent model of severe SCI. Use of a stereotactic frame and computer controlled impactor allows for creation of reproducible injury. Hypothermia and urinary tract infection pose significant challenges in the post-operative period. Careful monitoring of animals with daily weight recording and bladder expression allows for early detection of post-operative complications. The functional results of this contusion model are equivalent to transection models. The contusion model can be utilized to evaluate the efficacy of both neuroprotective and neuroregenerative approaches.

Choice of appropriate injury model is crucial for preclinical evaluation of novel treatments for spinal cord injury (SCI).1,2,13 In a recent survey of physicians and scientists in the field of neurotrauma contusion model, as opposed to hemisection or complete transection models, was universally accepted to be clinically relevant.8 This opinion is based on the observation that majority of spinal cord injury in humans is contusive in nature.10 The biology of contusion also appears to be different from hemisection or transection models.11 Iseda, et al. compared the effect of intraspinal chondroitinase ABC injection on ....

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1. Preparation Before Spinal Cord Injury

The surgical instruments required for this procedure are scalpel, pickups with and without teeth, hemostats, self retaining retractors, fine tip rongeurs, needle driver, absorbable sutures, and skin clip applicators. Other surgical supplies required are surgical drapes, sterile sheets for surgical field, gauze sponges, cotton-tip applicators, and metallic foil. Autoclave the surgical instruments and supplies prior to the surgery. Use the individual set of.......

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Lesion Volume

We have obtained large and consistent lesion volumes by following the technique described above. Using a Luxol fast blue staining a mean lesion volume of 2.04 mm3 (95% CI 1.9-2.18) (n = 5 animals) was obtained. Figure 2 shows mean lesion volume with a representative staining using Luxol fast blue through the lesion epicenter.

Functional Scores

The behavioral scores as measured by the Basso, Beattie, Bre.......

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Several novel treatments have recently shown early promise in the field of SCI research.3 Careful evaluation of these treatments is essential in clinically relevant model of SCI to select strategies with maximum translational potential. A scheme of grading was recently developed to evaluate the strength of preclinical studies.9 This scheme emphasized the importance of utilizing contusion model of severe SCI. Here we describe such a contusion model of severe SCI with consistent lesion volumes and fun.......

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The authors are grateful to Dr. N. Banik and Dr. D. Mitchell for their guidance in the development of this model.

....

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Name Company Catalog Number Comments
Instrument/Drugs Company Cat # Comments
Computer controlled impactor Leica or the Infinite Horizons (formerly OSU) impactor
Surgical instruments
Scissors Fine Science Tools Inc 14094-11 or 14060-09
Forceps Fine Science Tools Inc 11006-12 and 11027-12 or 11506-12
Hemostats Fine Science Tools Inc 13009-12
Retractors Fine Science Tools Inc 17011-10
Rongeurs Fine Science Tools Inc 16020-14
Needle driver Fine Science Tools Inc 12001-13
Stereotactic frame Leica or RWD Life Science Co. or TSE systems
Buprinorphine
Baytril Bayer
Ketamine

  1. Blesch, A., Tuszynski, M. H. Spinal cord injury: plasticity, regeneration and the challenge of translational drug development. Trends Neurosci. 32, 41-47 (2009).
  2. Dobkin, B. H. Curiosity and cure: translational research strategies for neural repair-mediated rehabilitation. Dev. Neurobiol. 67, 1133-1147 (2007).
  3. Fehlings, M. G., Cadotte, D. W., Fehlings, L. N. A series of systematic reviews on the treatment of acute spinal cord injury: a foundation for best medical practice. J. Neurotrauma. 28, 1329-1333 (2011).
  4. Iseda, T., Okuda, T., Kane-Goldsmith, N., et al. Single, high-dose intraspinal injection of chondroitinase reduces glycosaminoglycans in injured spinal cord and promotes corticospinal axonal regrowth after hemisection but not contusion. J. Neurotrauma. 25, 334-349 (2008).
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  8. Kwon, B. K., Hillyer, J., Tetzlaff, W. Translational research in spinal cord injury: a survey of opinion from the SCI community. J. Neurotrauma. 27, 21-33 (2010).
  9. Kwon, B. K., Okon, E. B., Tsai, E., et al. A grading system to evaluate objectively the strength of pre-clinical data of acute neuroprotective therapies for clinical translation in spinal cord injury. J. Neurotrauma. 28, 1525-1543 (2011).
  10. Norenberg, M. D., Smith, J., Marcillo, A. The pathology of human spinal cord injury: defining the problems. J. Neurotrauma. 21, 429-440 (2004).
  11. Siegenthaler, M. M., Tu, M. K., Keirstead, H. S. The extent of myelin pathology differs following contusion and transection spinal cord injury. J. Neurotrauma. 24, 1631-1646 (2007).
  12. Talac, R., Friedman, J. A., Moore, M. J., et al. Animal models of spinal cord injury for evaluation of tissue engineering treatment strategies. Biomaterials. 25, 1505-1510 (2004).
  13. Tator, C. H. Review of treatment trials in human spinal cord injury: issues, difficulties, and recommendations. Neurosurgery. 59, 957-982 (2006).

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