Spinal Cord Injuries in Dogs Part II: Standards of Care, Prognosis and New Perspectives

Open access


Severe spinal cord injuries (SCI), causing physical handicaps and accompanied by many serious complications, remains one of the most challenging problems in both, human and veterinary health care practices. The central nervous system in mammals does not regenerate, so the neurological deficits in a dog following SCI persists for the rest of its life and the affected animals display an image of permanent suffering. Diagnostics are based on: neurological examination, plain x-rays of vertebral column, x-rays of the vertebral column following intrathecal administration of a water-soluble contrast medium (myelography), x-rays of the vertebral column following epidural administration of a contrast medium (epidurography), computed tomography (CT) and/or magnetic resonance imaging (MRI). Currently, only limited therapeutic measures are available for the dogs with SCIs. They include: the administration of methylprednisolone sodium succinate (MPSS) during the acute stage; early spinal cord decompression; stabilisation of vertebral fractures or luxations; prevention and treatment of complications, and expert rehabilitation. Together with the progress in the understanding of pathophysiologic events occurring after SCI, different therapeutic strategies have been instituted, including the local delivery of MPSS, the utilisation of novel pharmacological agents, hypothermia, and stem/precursor cell transplantation have all been tested in the experimental models and preclinical trials with promising results. The aim of this review is the presentation of the generally accepted methods of diagnostics and management of dogs with SCIs, as well as to discuss new therapeutic modalities. The research strategy involved a PubMed, Medline (Ovid), Embase (Ovid) and ISI Web of Science literature search from January 2001 to December 2017 using the term “spinal cord injury”, in the English language literature; also references from selected papers were scanned and relevant articles included.

1. Adams, M. M., Hicks, A. L., 2005: Spasticity after spinal cord injury. Spinal Cord, 43, 577—586.

2. Akhtar, A. Z., Pippin, J. J., Sandusky, C. B., 2008: Animal models in spinal cord injury: a review. Rev. Neurosci., 19, 47—60.

3. Badner, A., Vawda, R., Laliberte, A., Hong, J., Mikhail, M., Jose, A., et al., 2016: Early intravenous delivery of human brain stromal cells modulates systemic inflammation and leads to vasoprotection in traumatic spinal cord injury. Stem Cells Transl. Med., 5, 991—1003.

4. Bockurt, G., Mothe, A. J., Zahir, T., Kim, H., Shoichet, M. L., Tator, C. H., 2010: Chitosan channels containing spinal cord-derived stem/progenitor cells for repair of subacute spinal cord injury in the rat. Neurosurgery, 67, 1733—1744.

5. Borrie, S. C., Baeumer, B. E., Badtlow, C. E., 2012: The nogo-66 receptor family in the intact and diseased CNS. Cell Tissue Res., 349, 105—117.

6. Bracken, M. B., 2012: Steroids for acute spinal cord injury. Review. Cochrane Database Syst. Rev., 1, Art. No.: CD001046.

7. Brisson, B. A., 2010: Intervertebral disc disease in dogs. Vet. Clin. North Am. Small Anim. Pract., 40, 829—858.

8. Brock, J., Rosenzweig, W. E., Blesch, A., Moseanko, R., Havton, L., Edgerton, V., et al., 2012: Local and remote growth factor effects after primate spinal cord injury. J. Neurosci., 30, 9728—9737.

9. Bruce, C. W., Brisson, B. A., Gyselinck, K., 2008: Spinal fracture and luxation in dogs and cats: a retrospective evaluation of 95 cases. Vet. Comp. Orthop. Traumatol., 21, 280—284.

10. Cauzimille, L., Kornegay, J. N., 1996: Fibrocartilaginous embolism of the spinal cord in dogs: Review of 36 histologically confirmed cases and retrospective study of 26 suspected cases. J. Vet. Intern. Med., 10, 241—245.

11. Devaux, S., Cizkova, D., Quamico, J., Franck, J., Nataf, S., Pays, L., et al., 2016: Proteomic analysis of the spatio-temporal based molecular kinetics of acute spinal cord injury identifies a time- and segment-specific window for effective tissue repair. Moll. Cell. Proteomics, 15, 2641—2670.

12. Dewey, C. W., 2008: A Practical Guide to Canine and Feline Neurology. 2nd edn., Iowa State University Press, Ames, Iowa, USA, 706 pp.

13. Dumont, R. J., Okonkwo, D. O., Verma, S., Hurlbert, R. J., Boulos, P. T., Ellegala, D. B., et al., 2001: Acute spinal cord injury, Part I: Pathophysiologic mechanisms. Clin. Neuropharm., 24, 254—264.

14. Eminaga, S., Palus, V., Cherubini, G. B., 2011: Acute spinal cord injury in the cats: causes, treatment and prognosis. J. Feline Med. Surg., 13, 850—862.

15. Filbin, M. T., 2003: Myelin-associated inhibitors of axonal regeneration in the adult mammalian CNS. Nat. Rev. Neurosci., 4, 703—713.

16. Fletcher, T. F., 2013: Spinal cord and meninges. In Evans, H. P., de Lahunta, A., (Eds.): Miller’s Anatomy of the Dog. 4th edn., Elsevier, Saunders, St. Louis, USA, 589—610.

17. Fouad, K., Ghosh, M., Vavrek, R., Tse, A. D., Pearse, D. D., 2009: Dose and chemical modification considerations for continuous cyclic AMP analog delivery to the injured CNS. J. Neurotrauma, 26, 733—740.

18. Fraga, J. S., Silva, N. A., Lourenco, A. S., Gincalves, V., Neves, N. M., Reis, R. L., et al., 2013: Unveiling the effects of the secretome of mesenchymal progenitors from the umbilical cord in different neuronal cell populations. Biochimie, 95, 2297—2303.

19. Frood, R. T., 2011: The use of treadmill training to recover locomotor ability in patients with spinal cord injury. Biosci. Hor., 4, 108—117.

20. Galandiuk, S., Raque, C., Appel, S., Polk, jr., H. C., 1993: The two-edged sword of large-dose steroids for spinal cord trauma. Ann. Surg., 218, 419—427.

21. Gandini, G., Cizinauskas, S., Lang, J., Fatzer, R., Jaggy, A., 2003: Fibrocartilaginous embolism in 75 dogs: clinical findings and factors influencing the recovery rate. J. Small Anim. Pract., 44, 76—80.

22. Gedrova, S., Galik, J., Marsala, M., Zavodska, M., Pavel, J., Sulla, I., 2018: Neuroprotective effect of local hypothermia in a computer-controlled compression model in minipig: correlation of tissue sparing along the rostro-caudal axis with neurological outcome. Exp. Therap. Med., 15, 254—270.

23. Grulova, I., Slovinska, L., Nagyova, M., Cizek, M., Cizkova, D., 2013: The effect of hypothermia on sensory-motor function and tissue sparing after spinal cord injury. Spine J., 13, 1881—1891.

24. Haisma, J. A., van der Woude, L. H., Stam, H. J., Bergen, M. P., Sluis, T. A., Post, M. W., et al., 2007: Complications following spinal cord injury: occurrence and risk factors in a longitudinal study during and after in patient’s rehabilitation. J. Rehab. Med., 39, 393—398.

25. Hanseobout, R. R., Hansebout, C. R., 2014: Local cooling for traumatic spinal cord injury: outcomes in 20 patients and review of literature. J. Neurosurg. Spine, 20, 550—561.

26. Harkema, S. J., Schmidt-Read, M., Lorenz, D. J., Edgerton, V. R., Behrman, A. L., 2012: Balance and ambulation improvements in individuals with chronic incomplete spinal cord injury using locomotor training-based rehabilitation. Arch. Phys. Med. Rehabilit., 93, 1508—1511.

27. Henke, D., Vandevelde, M., Doher, M. G., Stockli, M., Forterre, F., 2013: Correlations between severity of clinical signs and histopathological changes in 60 dogs with spinal cord injury associated with acute thoracolumbar intervertebral disc disease. Vet. J., 198, 70—75.

28. Hess, C. W., 2005: Nicht-traumatische akute Querschnittsyndrome. Praxis (Basel), 94, 1151—1159.

29. Hulbert, R. J., Hadley, M. N., Walters, B. C., Aarabi, B., Dhall, S. S., Gelb, D. E., et al., 2013: Pharmacological therapy for acute spinal cord injury. Neurosurgery, 72, 93—105.

30. Ilkiv, J. E., Turner, D. M., Howlett, C. R., 1987: Infestations in the dog by the paralysis tick Ixodes holocyclus. 1. Clinical and histological findings. Aust. Vet. J., 64, 137—139.

31. Jeffery, N. D., Hamilton, L., Granger, N., 2011: Designing clinical trials in canine spinal cord injury as a model to translate successful laboratory interventions into clinical practice. Vet. Rec., 168, 102—107.

32. Jeong, S. Y., Seol, D. W., Li, F. C., Chen, Q. X., 2008: The role of mitochondria in apoptosis. BMB Reports, 41, 11—22.

33. Kabu, S., Gao, Y., Kwon, B. K., 2015: Drug delivery, cell based therapies, and tissue engineering approaches for spinal cord injury. J. Control. Rel., 219, 141—154.

34. Kakulas, B. A., 2004: Neuropathology: the foundation for new treatments in spinal cord injury. Spinal Cord, 42, 549—563.

35. Kim, Y. T., Caldwell, J. M., Bellamkonda, R. V., 2009: Nanoparticle-mediated local delivery of methylprednisolone after spinal cord injury. Biomaterials, 30, 2582—2590.

36. Kruger, E. A., Pires, M., Ngann, Y., Sterling, M., Rubay, S., 2013: Comprehensive management of pressure ulcers in spinal cord injury: current concepts and future trends. J. Spin. Cord Med., 36, 572—585.

37. Kwon, B. K., Okon, E., Hillyer, J., Mann, C., Baptiste, D., Weaver, L. C., et al., 2011: A systematic review of non-invasive pharmacologic neuroprotective treatments for acute spinal cord injury. J. Neurotrauma, 28, 1545—1588.

38. Lee, J. Y., Kim, H. S., Choi, S. Y., Oh, T. H., Ju, B. G., Yune, T. Y., 2012: Valproic acid attenuates blood-spinal cord barrier disruption by inhibiting matrix metalloproteinase-9 activity and improves functional recovery after spinal cord injury. J. Neurochem., 121, 818—829.

39. Lee, J. Y., Choi, S. Y., Oh, T. H., Yune, T. Y., 2012: 17β-estradiol inhibits apoptotic cell death of oligodendrocytes by inhibiting Rhoa-JNK3 activation after spinal cord injury. Endocrinology, 153, 3815—3827.

40. Levine, G. J., Levine, J. M., Budke, C. M., Kerwin, S. C., Au, J., Vinayak, A., et al., 2009: Description and repeatability of a newly developed spinal cord injury scale for dogs. Prev. Vet. Med., 89, 121—127.

41. Lin, M. S., Lee, Y. H., Chiu, W. T., Hung, K. S., 2011: Curcumin provides neuroprotection after spinal cord injury. J. Surg. Res., 166, 280—289.

42. Liu, W. M., Wu, J. Y., Li, F. C., Vhen, Q. X., 2011: Ion channel blockers and spinal cord injury. J. Neurosci. Res., 89, 791—801.

43. Lo, T. P., Cho, K. S., Garg, M. S., Lynch, M. P., Marcillo, A. E., Koivisto, D. L., et al., 2009: Systemic hypothermia improves histological and functional outcome after cervical spinal cord contusion in rats. J. Comp. Neurol., 514, 433—448.

44. Low, K., Culbertson, M., Bradke, F., Tessier-Lavigne, M., Tuszynski, M. H., 2008: Netrin-1 is a novel myelin-associated inhibitor to axon growth. J. Neurosci., 28, 1099—1108.

45. Mack, E. H., 2013: Neurogenic shock. Open Ped. Med. J., 7 (Suppl. 1: M4), 16—18.

46. McKee, W. M., Downes, C. J., Pink, J. J., Gemmill, T. J., 2010: Presumptive exercise-associated peracute thoracolumbar disc extrusion in 48 dogs. Vet. Rec., 166, 523—528.

47. McKinley, W., Santos, K., Meade, M., Brooke, K., 2007: Incidence and outcomes of spinal cord injury clinical syndromes. J. Spinal Cord Med., 30, 215—224.

48. McMurray, G., Casey, J. H., Naylor, A. M., 2006: Animal models in urologic disease and sexual dysfunction. Br. J. Pharm., 147, S52—S79.

49. Nakamoto, Y., Ozawa, T., Katanabe, K., Nishiya, K., Yasuda, N., Mashita, T., et al., 2009: Fibrocartilaginous embolism of the spinal cord diagnosed by characteristic clinical findings and magnetic resonance imaging in 26 dogs. J. Vet. Med. Sci., 71, 171—176.

50. Nakano, R., Edamura, K., Sugiya, H., Narita, T., Okabayashi, K., Moritomo, T., et al., 2013: Evaluation of mRNA expression levels and electrophysiological function of neuronlike cells derived from canine bone marrow stromal cells. Am. J. Vet. Res., 74, 1311—1320.

51. Nishida, H., Nakayama, M., Tanaka, H., Kitamura, M., Hatoya, S., Sugiura, K., et al., 2011: Evaluation of transplantation of autologous bone marrow stromal cells into the cerebrospinal fluid for treatment of chronic spinal cord injury in dogs. Am. J. Vet. Res., 72, 1118—1123.

52. Noble, L. J., Donovan, F., Igarashi, T., Goussev, S., Werb, Z., 2002: Matrix metalloproteinases limit functional recovery after spinal cord injury by modulation of early vascular events. J. Neurosci., 22, 7526—7535.

53. Olby, N., 2010: The pathogenesis and treatment of acute spinal cord injuries in dogs. Vet. Clin. N. Am. Small Anim. Pract., 40, 791—807.

54. Ormond, D. R., Peng, H., Zeman, R., Das, K., Murali, R., Jhanwar-Uniyal, M., 2012: Recovery from spinal cord injury using naturally occurring anti-inflammatory compound curcumin: laboratory investigation. J. Neurosurg. Spine, 16, 497—503.

55. Penning, V., Platt, S. R., Dennis, R., Capello, R., Adams, V., 2006: Association of spinal cord compression seen on magnetic resonance imaging with clinical outcome in 67 dogs with thoracolumbar intervertebral disc extrusion. J. Small Anim. Pract., 47, 644—655.

56. Quian, T., Guo, X., Levi, A. D., Vanni, S., Shebert, R. T., Sipski, M. L., 2005: High-dose methylprednisolone may cause myopathy in acute spinal cord injury patients. Spinal Cord, 43, 199—203.

57. Risio, L. D., Platt, S. R., 2010: Fibrocartilaginous embolic myelopathy in small animals. Vet. Clin. North Am. Small Anim. Pract., 40, 859—869.

58. Rowland, J. W., Hawryluk, G. W. J., Kwon, B., Fehlings, M. G., 2008: Current status of acute spinal cord injury pathophysiology and emerging therapies: promise on the horizon. Neurosurg. Focus, 25, E2.

59. Saganova, K., Orendacova, J., Cizkova, D., Vanicky, I., 2008: Limited minocycline neuroprotection after balloon-compression spinal cord injury in the rat. Neurosci. Letters, 433, 246—249.

60. Samantaray, S., Das, A., Thakore, N. P., Matzelle, D. D., Reiter, R. J., Ray, L. K., et al., 2009: Therapeutic potencial of melatonin in traumatic central nervous system injury. J. Pineal Res., 47, 134—142.

61. Sarmento, C. A. P., Rodrigues, M. N., Bocabello, R. Z., Mess, A. M., Miglino, M. A., 2014: Pilot study: bone marrow stem cells as a treatment for dogs with chronic spinal cord injury. Reg. Med. Res., 2, 9.

62. Silva, N. A., Sousa, N., Reis, R. L., Salgado, A. J., 2014: From basics to clinical: a comprehensive review on spinal cord injury. Progr. Neurobiol., 114, 25—57.

63. Srugo, I., Aroch, I., Christopher, M. M., Chai, O., Goralnik, I., Bdolah-Abram, I., et al., 2011: Signs and outcome in acute nonambulatory thoracolumbar disc disease in dogs. J. Vet. Intern., Med., 25, 846—855.

64. Steward, O., Popovich, P. G., Dietrich, W. D., Kleitman, N., 2012: Replication and reproducibility in spinal cord injury research. Exp. Neurol., 233, 597—605.

65. Šulla, I., Balik, V., Petrovičová, J., Almášiová, V., Holovská, K, Oroszová, Z., 2016: A rat spinal cord injury experimental model. Folia Veterinaria, 60, 41—46.

66. Tsao, T. Y., Chen, E. L., Tsai, W. C., 2009: Steroids for acute spinal cord injury: revealing silent pathology. Lancet, 374 (9688), 500.

67. Waters, R. L., Adkins, R. H., Yakura, J. S., 1991: Definition of complete spinal cord injury. Spinal Cord, 29, 573—581.

68. Webb, A. A., Ngan, S., Fowler, D. J., 2010: Spinal cord injury I: a synopsis of the basic science. Can. Vet. J., 51, 485—492.

69. Webb, A. A., Ngan, S., Fowler, D. J., 2010: Spinal cord injury II: prognostic indicators, standards of care, and clinical trials. Can. Vet. J., 51, 598—604.

70. Wewetzer, K., Radtke, C., Kocsis, J., Baumgärtner, W., 2011: Species-specific control of cellular proliferation and the impact of large animal models for the use of olfactory ensheathing cells and Schwann cells in spinal cord repair. Exp. Neurol., 229, 80—87.

71. Wilson, J. R., Foergione, N., Fehlings, M. G., 2013: Emerging therapies for acute traumatic spinal cord injury. Canad. Med. Assoc. J., 71, 281—299.

72. Wu, K. L. H., Hsu, C., Chan, J. Y. J., 2009: Nitric oxide and superoxide anion differentially activate poly(ADP-ribose) polymerase-1 and Bax to induce nuclear translocation of apoptosis inducing factor and mitochondrial release of cytochrome C after spinal cord injury. J. Neurotrauma, 26, 965—977.

73. Xu, J., Fan, G., Chen, S., Wu, Y., Xu, M., Hsu, C. Y., 1998: Methylprednisolone inhibition of TNF-alpha expression and NF-KB activation after spinal cord injury in rats. Brain Res. Mol. Brain Res., 59, 135—142.

74. Ying, Z., Roy, R. R., Edgerton, V. R., Gómez-Pinilla, F., 2005: Exercise restores levels of neurotrophins and synaptic plasticity following spinal cord injury. Exp. Neurol., 193, 411—419.

75. Zaki, F. A., Prata, R. G., 1976: Necrotizing myelopathy secondary to embolization of herniated intervertebral disk material in the dog. J. Am. Vet. Med. Assoc., 169, 222—228.

76. Zhou, X., He, X., Ren, Y., 2014: Function of microglia and macrophages in secondary damage after spinal cord injury. Neural Reg. Res., 9, 1787—1795.

77. Zhu, H., Feng, Y. P., Wise, Y., Yon, S. W., Shen, X. F., Liu, Y. S., et al., 2008: Early neurosurgical intervention of spinal cord contusion: an analysis of 30 cases. Chin. Med. J., 121, 2473—2478.

Journal Information


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 354 289 15
PDF Downloads 263 219 12