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Cervical Hemicontusion Spinal Cord Injury Model

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Animal Models of Acute Neurological Injury

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.

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References

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  28. Berntson GG, Jang JF, Ronca AE. Brainstem systems and grooming behaviors. Ann N Y Acad Sci. 1988;525:350–62.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

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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.

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Correspondence to Warren J. Alilain or John C. Gensel .

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Warren, P.M. et al. (2019). Cervical Hemicontusion Spinal Cord Injury Model. 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_31

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  • DOI: https://doi.org/10.1007/978-3-030-16082-1_31

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