Advertisement

Cervical Hemicontusion Spinal Cord Injury Model

  • Philippa M. Warren
  • Basem I. Awad
  • Davina V. Gutierrez
  • Kevin C. Hoy
  • Michael P. Steinmetz
  • Warren J. AlilainEmail author
  • John C. GenselEmail author
Chapter
Part of the Springer Series in Translational Stroke Research book series (SSTSR)

Abstract

This chapter describes a unilateral cervical spinal cord contusion model that causes ipsilateral respiratory and/or forelimb motor deficits. Additional techniques are presented to assess forelimb function via grooming and paw placement tasks, as well as respiratory activity using additional lesion techniques that remove descending compensatory respiratory motor control. Cervical injury is the most common type of human spinal cord injury. Modeling functions of highest priority for this spinal cord injured population (i.e. respiratory and arm/hand control) provides a translational approach for the evaluation of potentially therapeutic interventions.

Keywords

Breathing Diaphragm Rat Phrenic Hemisection 

Notes

Acknowledgements

This study was supported by grants to WJA from the International Spinal Research Trust and the Craig H. Neilsen Foundation. JCG was supported, in part, by the Paralysis Project of America. Additional support comes from MetroHealth Medical Center in Cleveland, Ohio and the Spinal Cord and Brain Injury Research Center at the University of Kentucky. BIA was supported by the Egyptian Governmental Scholarship and PMW by the International Spinal Research Trust and Wings for Life.

Disclosures: The authors do not have any competing financial interests to disclose.

References

  1. 1.
    DeVivo MJ, Chen Y. Trends in new injuries, prevalent cases, and aging with spinal cord injury. Arch Phys Med Rehabil. 2011;92:332–8.  https://doi.org/10.1016/j.apmr.2010.08.031.CrossRefPubMedGoogle Scholar
  2. 2.
    Allen AR. Surgery of experimental lesion of spinal cord equivalent to crush injury of fracture dislocation of spinal column: a preliminary report. J Am Med Assoc. 1911;LVII(11):878–80.CrossRefGoogle Scholar
  3. 3.
    Trivedi A, Olivas AD, Noble-Haeusslein LJ. Inflammation and spinal cord injury: infiltrating leukocytes as determinants of injury and repair processes. Clin Neurosci Res. 2006;6:283–92.  https://doi.org/10.1016/j.cnr.2006.09.007.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    DeVivo MJ. Epidemiology of traumatic spinal cord injury: trends and future implications. Spinal Cord. 2012;50:365–72.  https://doi.org/10.1038/sc.2011.178.CrossRefPubMedGoogle Scholar
  5. 5.
    Gensel JC, Tovar CA, Hamers FPT, et al. Behavioral and histological characterization of unilateral cervical spinal cord contusion injury in rats. J Neurotrauma. 2006;23:36–54.  https://doi.org/10.1089/neu.2006.23.36.CrossRefPubMedGoogle Scholar
  6. 6.
    Awad BI, Warren PM, Steinmetz MP, Alilain WJ. The role of the crossed phrenic pathway after cervical contusion injury and a new model to evaluate therapeutic interventions. Exp Neurol. 2013;248:398–405.  https://doi.org/10.1016/j.expneurol.2013.07.009.CrossRefPubMedGoogle Scholar
  7. 7.
    Streijger F, Beernink TMJ, Lee JHT, et al. Characterization of a cervical spinal cord hemicontusion injury in mice using the infinite horizon impactor. J Neurotrauma. 2013;30:869–83.  https://doi.org/10.1089/neu.2012.2405.CrossRefPubMedGoogle Scholar
  8. 8.
    Scheff SW, Rabchevsky AG, Fugaccia I, et al. Experimental modeling of spinal cord injury: characterization of a force-defined injury device. J Neurotrauma. 2003;20:179–93.  https://doi.org/10.1089/08977150360547099.CrossRefPubMedGoogle Scholar
  9. 9.
    Ferguson AR, Irvine K-A, Gensel JC, et al. Derivation of multivariate syndromic outcome metrics for consistent testing across multiple models of cervical spinal cord injury in rats. PLoS One. 2013;8:e59712.  https://doi.org/10.1371/journal.pone.0059712.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Goshgarian HG, Ellenberger HH, Feldman JL. Decussation of bulbospinal respiratory axons at the level of the phrenic nuclei in adult rats: a possible substrate for the crossed phrenic phenomenon. Exp Neurol. 1991;111:135–9.CrossRefGoogle Scholar
  11. 11.
    Goshgarian HG, Rafols JA. The ultrastructure and synaptic architecture of phrenic motor neurons in the spinal cord of the adult rat. J Neurocytol. 1984;13:85–109.CrossRefGoogle Scholar
  12. 12.
    Inskip JA, Ramer LM, Ramer MS, Krassioukov AV. Autonomic assessment of animals with spinal cord injury: tools, techniques and translation. Spinal Cord. 2009;47:2–35.  https://doi.org/10.1038/sc.2008.61.CrossRefPubMedGoogle Scholar
  13. 13.
    Krassioukov A. Autonomic function following cervical spinal cord injury. Respir Physiol Neurobiol. 2009;169:157–64.  https://doi.org/10.1016/j.resp.2009.08.003.CrossRefPubMedGoogle Scholar
  14. 14.
    Baussart B, Stamegna JC, Polentes J, et al. A new model of upper cervical spinal contusion inducing a persistent unilateral diaphragmatic deficit in the adult rat. Neurobiol Dis. 2006;22:562–74.  https://doi.org/10.1016/j.nbd.2005.12.019.CrossRefPubMedGoogle Scholar
  15. 15.
    Choi H, Liao W-L, Newton KM, et al. Respiratory abnormalities resulting from midcervical spinal cord injury and their reversal by serotonin 1A agonists in conscious rats. J Neurosci. 2005;25:4550–9.  https://doi.org/10.1523/JNEUROSCI.5135-04.2005.CrossRefPubMedGoogle Scholar
  16. 16.
    el-Bohy AA, Schrimsher GW, Reier PJ, Goshgarian HG. Quantitative assessment of respiratory function following contusion injury of the cervical spinal cord. Exp Neurol. 1998;150:143–52.  https://doi.org/10.1006/exnr.1997.6757.CrossRefPubMedGoogle Scholar
  17. 17.
    Golder FJ, Fuller DD, Lovett-Barr MR, et al. Breathing patterns after mid-cervical spinal contusion in rats. Exp Neurol. 2011;231(1):97–103.  https://doi.org/10.1016/j.expneurol.2011.05.020.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Lane MA, Lee K-Z, Salazar K, et al. Respiratory function following bilateral mid-cervical contusion injury in the adult rat. Exp Neurol. 2012;235(1):197–210.  https://doi.org/10.1016/j.expneurol.2011.09.024.CrossRefPubMedGoogle Scholar
  19. 19.
    Nicaise C, Hala TJ, Frank DM, et al. Phrenic motor neuron degeneration compromises phrenic axonal circuitry and diaphragm activity in a unilateral cervical contusion model of spinal cord injury. Exp Neurol. 2012;235:539–52.  https://doi.org/10.1016/j.expneurol.2012.03.007.CrossRefPubMedGoogle Scholar
  20. 20.
    Stamegna JC, Felix MS, Roux-Peyronnet J, et al. Nasal OEC transplantation promotes respiratory recovery in a subchronic rat model of cervical spinal cord contusion. Exp Neurol. 2011;229:120–31.  https://doi.org/10.1016/j.expneurol.2010.07.002.CrossRefPubMedGoogle Scholar
  21. 21.
    Vinit S, Stamegna J-C, Boulenguez P, et al. Restorative respiratory pathways after partial cervical spinal cord injury: role of ipsilateral phrenic afferents. Eur J Neurosci. 2007;25:3551–60.  https://doi.org/10.1111/j.1460-9568.2007.05619.x.CrossRefPubMedGoogle Scholar
  22. 22.
    Teasell RW, Mehta S, Aubut J-AL, et al. A systematic review of pharmacologic treatments of pain after spinal cord injury. Arch Phys Med Rehabil. 2010;91:816–31.  https://doi.org/10.1016/j.apmr.2010.01.022.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    McKenna JE, Prusky GT, Whishaw IQ. Cervical motoneuron topography reflects the proximodistal organization of muscles and movements of the rat forelimb: a retrograde carbocyanine dye analysis. J Comp Neurol. 2000;419:286–96.CrossRefGoogle Scholar
  24. 24.
    Šedý J, Urdzíková L, Jendelová P, Syková E. Methods for behavioral testing of spinal cord injured rats. Neurosci Biobehav Rev. 2008;32:550–80.  https://doi.org/10.1016/j.neubiorev.2007.10.001.CrossRefPubMedGoogle Scholar
  25. 25.
    Nielson JL, Guandique CF, Liu AW, et al. Development of a database for translational spinal cord injury research. J Neurotrauma. 2014;31:1789–99.  https://doi.org/10.1089/neu.2014.3399.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Nielson JL, Paquette J, Liu AW, et al. Topological data analysis for discovery in preclinical spinal cord injury and traumatic brain injury. Nat Commun. 2015;6:8581.  https://doi.org/10.1038/ncomms9581.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Bertelli JA, Mira JC. Behavioral evaluating methods in the objective clinical assessment of motor function after experimental brachial plexus reconstruction in the rat. J Neurosci Methods. 1993;46:203–8.CrossRefGoogle Scholar
  28. 28.
    Berntson GG, Jang JF, Ronca AE. Brainstem systems and grooming behaviors. Ann N Y Acad Sci. 1988;525:350–62.CrossRefGoogle Scholar
  29. 29.
    Schallert T, Fleming SM, Leasure JL, et al. CNS plasticity and assessment of forelimb sensorimotor outcome in unilateral rat models of stroke, cortical ablation, parkinsonism and spinal cord injury. Neuropharmacology. 2000;39:777–87.CrossRefGoogle Scholar
  30. 30.
    Liu Y, Kim D, Himes BT, et al. Transplants of fibroblasts genetically modified to express BDNF promote regeneration of adult rat rubrospinal axons and recovery of forelimb function. J Neurosci. 1999;19:4370–87.CrossRefGoogle Scholar
  31. 31.
    Ichihara K, Taguchi T, Sakuramoto I, et al. Mechanism of the spinal cord injury and the cervical spondylotic myelopathy: new approach based on the mechanical features of the spinal cord white and gray matter. J Neurosurg. 2003;99:278–85.PubMedGoogle Scholar
  32. 32.
    Amendola L, Corghi A, Cappuccio M, De Iure F. Two cases of Brown-Séquard syndrome in penetrating spinal cord injuries. Eur Rev Med Pharmacol Sci. 2014;18:2–7.PubMedGoogle Scholar
  33. 33.
    Popovich PG, Lemeshow S, Gensel JC, Tovar CA. Independent evaluation of the effects of glibenclamide on reducing progressive hemorrhagic necrosis after cervical spinal cord injury. Exp Neurol. 2012;233:615–22.  https://doi.org/10.1016/j.expneurol.2010.11.016.CrossRefPubMedGoogle Scholar
  34. 34.
    Simard JM, Popovich PG, Tsymbalyuk O, Gerzanich V. Spinal cord injury with unilateral versus bilateral primary hemorrhage—effects of glibenclamide. Exp Neurol. 2012;233:829–35.  https://doi.org/10.1016/j.expneurol.2011.11.048.CrossRefPubMedGoogle Scholar
  35. 35.
    Kwon BK, Okon E, Hillyer J, et al. A systematic review of non-invasive pharmacologic neuroprotective treatments for acute spinal cord injury. J Neurotrauma. 2011;28:1545–88.  https://doi.org/10.1089/neu.2009.1149.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Goshgarian HG. The crossed phrenic phenomenon: a model for plasticity in the respiratory pathways following spinal cord injury. J Appl Physiol. 2003;94:795–810.  https://doi.org/10.1152/japplphysiol.00847.2002.CrossRefPubMedGoogle Scholar
  37. 37.
    Porter WT. The path of the respiratory impulse from the bulb to the phrenic nuclei. J Physiol Lond. 1895;17:455–85.  https://doi.org/10.1113/jphysiol.1895.sp000553.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Alilain WJ, Silver J. Shedding light on restoring respiratory function after spinal cord injury. Front Mol Neurosci. 2009;2:18.  https://doi.org/10.3389/neuro.02.018.2009.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Vinit S, Darlot F, Stamegna J-C, et al. Long-term reorganization of respiratory pathways after partial cervical spinal cord injury. Eur J Neurosci. 2008;27:897–908.  https://doi.org/10.1111/j.1460-9568.2008.06072.x.CrossRefPubMedGoogle Scholar
  40. 40.
    Vinit S, Kastner A. Descending bulbospinal pathways and recovery of respiratory motor function following spinal cord injury. Respir Physiol Neurobiol. 2009;169:115–22.  https://doi.org/10.1016/j.resp.2009.08.004.CrossRefPubMedGoogle Scholar
  41. 41.
    Nicaise C, Frank DM, Hala TJ, et al. Early phrenic motor neuron loss and transient respiratory abnormalities after unilateral cervical spinal cord contusion. J Neurotrauma. 2013;30:1092–9.  https://doi.org/10.1089/neu.2012.2728.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Philippa M. Warren
    • 1
    • 2
  • Basem I. Awad
    • 1
    • 3
  • Davina V. Gutierrez
    • 1
  • Kevin C. Hoy
    • 1
  • Michael P. Steinmetz
    • 1
  • Warren J. Alilain
    • 1
    • 4
    • 5
    Email author
  • John C. Gensel
    • 4
    • 6
    Email author
  1. 1.Department of Neurosciences, MetroHealth Medical CenterCase Western Reserve University School of MedicineClevelandUSA
  2. 2.Department of NeurosciencesCase Western Reserve University School of MedicineClevelandUSA
  3. 3.Department of Neurological SurgeryMansoura University School of MedicineMansouraEgypt
  4. 4.Spinal Cord and Brain Injury Research CenterUniversity of KentuckyLexingtonUSA
  5. 5.Department of Anatomy and NeurobiologyUniversity of KentuckyLexingtonUSA
  6. 6.Department of PhysiologyUniversity of KentuckyLexingtonUSA

Personalised recommendations