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Using Naturally Occurring Spinal Cord Injury in Domestic Dogs to Explore Novel Therapeutic Options

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Animal Models of Spinal Cord Repair

Part of the book series: Neuromethods ((NM,volume 76))

Abstract

Modeling human disease in animals has traditionally been used to elucidate pathogenesis and test promising new approaches to treatment. This approach has now identified a plethora of interventions that ameliorate functional deficits associated with spinal cord injury (SCI) in rodents. A major current challenge is to translate these interventions into humans. However, there are several important differences between experimental SCI in rodents and the equivalent clinical condition in humans, chiefly that of lesion heterogeneity, which can result in failure to translate a statistically detectable effect in a laboratory into a benefit of sufficient magnitude to be of value to clinical patients. Here we show how veterinary clinical SCI cases can help in testing the feasibility and value of translating specific putative therapies from laboratory to clinic. Dogs commonly present with SCI, undergo similar diagnostic and therapeutic procedures as their human counterparts and have a similar prognosis. We show how effects on spinal cord function can be objectively and precisely quantified in clinical canine patients and discuss how this type of data provides a unique viewpoint with which to evaluate promising experimental interventions prior to initiating human clinical trials.

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References

  1. Allen AR (1911) Surgery of experimental lesion of spinal cord equivalent to crush injury of fracture dislocation of spinal column: a preliminary report. J Am Med Assoc 57:878–880

    Article  Google Scholar 

  2. Paoloni M, Khanna C (2008) Translation of new cancer treatments from pet dogs to humans. Nat Rev Cancer 8:147–156

    Article  PubMed  CAS  Google Scholar 

  3. Jeffery ND, Smith PM, Lakatos A, Ibanez C, Ito D, Franklin RJ (2006) Clinical canine spinal cord injury provides an opportunity to examine the issues in translating laboratory techniques into practical therapy. Spinal Cord 44:584–593

    Article  PubMed  CAS  Google Scholar 

  4. Tarlov IM, Klinger H, Vitale S (1953) Spinal cord compression studies. I. Experimental techniques to produce acute and gradual compression. AMA Arch Neurol Psychiatry 70:813–819

    Article  PubMed  CAS  Google Scholar 

  5. Tarlov IM, Klinger H (1954) Spinal cord compression studies. II. Time limits for recovery after acute compression in dogs. AMA Arch Neurol Psychiatry 71:271–290

    Article  PubMed  CAS  Google Scholar 

  6. Tarlov IM (1954) Spinal cord compression studies. III. Time limits for recovery after gradual compression in dogs. AMA Arch Neurol Psychiatry 71:588–597

    Article  PubMed  CAS  Google Scholar 

  7. Bassso DM, Beattie MS, Bresnahan JC (1995) A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma 12:1–21

    Article  Google Scholar 

  8. Basso DM, Beattie MS, Bresnahan JC, Anderson DK, Faden AI, Gruner JA et al (1996) MASCIS evaluation of open field locomotor scores: effects of experience and teamwork on reliability. Multicenter Animal Spinal Cord Injury Study. J Neurotrauma 13:343–359

    Article  PubMed  CAS  Google Scholar 

  9. Al-Mefty O, Harkey HL, Marawi I, Haines DE, Peeler DF, Wilner HI et al (1993) Experimental chronic compressive cervical myelopathy. J Neurosurg 79:550–561

    Article  PubMed  CAS  Google Scholar 

  10. Harkey HL, Al-Mefty O, Marawi I, Peeler DF, Haines DE, Alexander LF (1995) Experimental chronic compressive cervical myelopathy: effects of decompression. J Neurosurg 83:336–341

    Article  PubMed  CAS  Google Scholar 

  11. Assina R, Sankar T, Theodore N, Javedan SP, Gibson AR, Horn KM et al (2008) Activated autologous macrophage implantation in a large-animal model of spinal cord injury. Neurosurg Focus 25:E3

    Article  PubMed  Google Scholar 

  12. Rabinowitz RS, Eck JC, Harper CM Jr, Larson DR, Jimenez MA, Parisi JE et al (2008) Urgent surgical decompression compared to methylprednisolone for the treatment of acute spinal cord injury: a randomized prospective study in beagle dogs. Spine (Phila Pa 1976) 33:2260–2268

    Article  Google Scholar 

  13. Kim BG, Kang YM, Phi JH, Kim YH, Hwang DH, Choi JY et al (2010) Implantation of polymer scaffolds seeded with neural stem cells in a canine spinal cord injury model. Cytotherapy 12:841–845

    Article  PubMed  CAS  Google Scholar 

  14. Lee JH, Chang HS, Kang EH, Chung DJ, Choi CB, Hwang SH et al (2009) Percutaneous transplantation of human umbilical cord blood-derived multipotent stem cells in a canine model of spinal cord injury. J Neurosurg Spine 11:749–757

    Article  PubMed  Google Scholar 

  15. Lee JH, Chung WH, Kang EH, Chung DJ, Choi CB, Chang HS et al (2011) Schwann cell-like remyelination following transplantation of human umbilical cord blood (hUCB)-derived mesenchymal stem cells in dogs with acute spinal cord injury. J Neurol Sci 300:86–96

    Article  PubMed  Google Scholar 

  16. Lim JH, Byeon YE, Ryu HH, Jeong YH, Lee YW, Kim WH et al (2007) Transplantation of canine umbilical cord blood-derived mesenchymal stem cells in experimentally induced spinal cord injured dogs. J Vet Sci 8:275–282

    Article  PubMed  Google Scholar 

  17. Ryu HH, Lim JH, Byeon YE, Park JR, Seo MS, Lee YW et al (2009) Functional recovery and neural differentiation after transplantation of allogenic adipose-derived stem cells in a canine model of acute spinal cord injury. J Vet Sci 10:273–284

    Article  PubMed  Google Scholar 

  18. Hansen HJ (1951) A pathologic-anatomical interpretation of disc degeneration in dogs. Acta Orthop Scand 20:280–293

    Article  PubMed  CAS  Google Scholar 

  19. Hansen HJ (1952) A pathologic-anatomical study on disc degeneration in dog, with special reference to the so-called enchondrosis intervertebralis. Acta Orthop Scand Suppl 11:1–117

    Google Scholar 

  20. Jeffery ND (2010) Vertebral fracture and luxation in small animals. Vet Clin North Am Small Anim Pract 40:809–828

    Article  PubMed  Google Scholar 

  21. Brisson BA (2010) Intervertebral disc disease in dogs. Vet Clin North Am Small Anim Pract 40:829–858

    Article  PubMed  Google Scholar 

  22. Ball MU, McGuire JA, Swaim SF, Hoerlein BF (1982) Patterns of occurrence of disk disease among registered dachshunds. J Am Vet Med Assoc 180:519–522

    PubMed  CAS  Google Scholar 

  23. Webb AA, Ngan S, Fowler D (2010) Spinal cord injury II: Prognostic indicators, standards of care, and clinical trials. Can Vet J 51:598–604

    PubMed  Google Scholar 

  24. Blight AR, Decrescito V (1986) Morphometric analysis of experimental spinal cord injury in the cat: the relation of injury intensity to survival of myelinated axons. Neuroscience 19:321–341

    Article  PubMed  CAS  Google Scholar 

  25. Bunge RP, Puckett WR, Becerra JL, Marcillo A, Quencer RM (1993) 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 59:75–89

    PubMed  CAS  Google Scholar 

  26. Fehlings MG, Tator CH (1995) The relationships among the severity of spinal cord injury, residual neurological function, axon counts, and counts of retrogradely labeled neurons after experimental spinal cord injury. Exp Neurol 132:220–228

    Article  PubMed  CAS  Google Scholar 

  27. Smith PM, Lakatos A, Barnett SC, Jeffery ND, Franklin RJ (2002) Cryopreserved cells isolated from the adult canine olfactory bulb are capable of extensive remyelination following transplantation into the adult rat CNS. Exp Neurol 176:402–406

    Article  PubMed  CAS  Google Scholar 

  28. Nashmi R, Fehlings MG (2001) Changes in axonal physiology and morphology after chronic compressive injury of the rat thoracic spinal cord. Neuroscience 104:235–251

    Article  PubMed  CAS  Google Scholar 

  29. Schucht P, Raineteau O, Schwab ME, Fouad K (2002) Anatomical correlates of locomotor recovery following dorsal and ventral lesions of the rat spinal cord. Exp Neurol 176:143–153

    Article  PubMed  CAS  Google Scholar 

  30. Fletcher TF (1993) Spinal cord and meninges (Chapter 14). In: Evans EH (ed) Miller’s anatomy of the dog, 3rd edn. WB Saunders Co, Philadelphia

    Google Scholar 

  31. Woolam DH, Millen JW (1955) The arterial supply of the spinal cord and its significance. J Neurol Neurosurg Psychiatry 18:97–102

    Article  Google Scholar 

  32. Hagg T, Oudega M (2006) Degenerative and spontaneous regenerative processes after spinal cord injury. J Neurotrauma 23:264–280

    PubMed  Google Scholar 

  33. Zhang Z, Fujiki M, Guth L, Steward O (1996) Genetic influences on cellular reactions to spinal cord injury: a wound-healing response present in normal mice is impaired in mice carrying a mutation (WldS) that causes delayed Wallerian degeneration. J Comp Neurol 371:485–495

    Article  PubMed  CAS  Google Scholar 

  34. Inman DM, Steward O (2003) Physical size does not determine the unique histopathological response seen in the injured mouse spinal cord. J Neurotrauma 20:33–42

    Article  PubMed  Google Scholar 

  35. Steward O, Zheng B, Tessier-Lavigne M (2003) False resurrections: distinguishing regenerated from spared axons in the injured central nervous system. J Comp Neurol 459:1–8

    Article  PubMed  Google Scholar 

  36. Behr VC, Weber T, Neuberger T, Vroemen M, Weidner N, Bogdahn U et al (2004) High-resolution MR imaging of the rat spinal cord in vivo in a wide-bore magnet at 17.6 Tesla. MAGMA 17:353–358

    Article  PubMed  CAS  Google Scholar 

  37. Ko HY, Park JH, Shin YB, Baek SY (2004) Gross quantitative measurements of spinal cord segments in human. Spinal Cord 42:35–40

    Article  PubMed  Google Scholar 

  38. Dietz V (2009) Body weight supported gait training: from laboratory to clinical setting. Brain Res Bull 78:I–VI

    Article  PubMed  CAS  Google Scholar 

  39. Garcia-Alias G, Barkhuysen S, Buckle M, Fawcett JW (2009) Chondroitinase ABC treatment opens a window of opportunity for task-specific rehabilitation. Nat Neurosci 12:1145–1151

    Article  PubMed  CAS  Google Scholar 

  40. Savic G, Bergström EM, Frankel HL, Jamous MA, Jones PW (2007) Inter-rater reliability of motor and sensory examinations performed according to American Spinal Injury Association standards. Spinal Cord 45:444–451

    Article  PubMed  CAS  Google Scholar 

  41. Jeffery ND, 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

    Article  PubMed  CAS  Google Scholar 

  42. Webb AA, Jeffery ND, Olby NJ, Muir GD (2004) Behavioural analysis of the efficacy of treatments for injuries to the spinal cord in animals. Vet Rec 155:225–230

    Article  PubMed  CAS  Google Scholar 

  43. Hoerlein BF (1953) Intervertebral disc protrusions in the dog. I. Incidence and pathological lesions. Am J Vet Res 14:260–269

    PubMed  CAS  Google Scholar 

  44. Olby NJ, De Risio L, Muñana KR, Wosar MA, Skeen TM, Sharp NJ et al (2001) Development of a functional scoring system in dogs with acute spinal cord injuries. Am J Vet Res 62:1624–1628

    Article  PubMed  CAS  Google Scholar 

  45. Levine JM, Fosgate GT, Chen AV, Rushing R, Nghiem PP, Platt SR et al (2009) Magnetic resonance imaging in dogs with neurologic impairment due to acute thoracic and lumbar intervertebral disk herniation. J Vet Intern Med 23:1220–1226

    Article  PubMed  CAS  Google Scholar 

  46. Granger N, Jeffery ND (2009) MRI findings in severe chronic spinal cord injury of dogs. In: British Small Animal Veterinary Association Congress Proceeding, Brimingham

    Google Scholar 

  47. Ito D, Matsunaga S, Jeffery ND, Sasaki N, Nishimura R, Mochizuki M et al (2005) Prognostic value of magnetic resonance imaging in dogs with paraplegia caused by thoracolumbar intervertebral disk extrusion: 77 cases (2000–2003). J Am Vet Med Assoc 227:1454–1460

    Article  PubMed  Google Scholar 

  48. Holliday TA (1992) Electrodiagnostic examination. Somatosensory evoked potentials and electromyography. Vet Clin North Am Small Anim Pract 22:833–857

    PubMed  CAS  Google Scholar 

  49. Poncelet L, Michaux C, Balligand M (1993) Somatosensory potentials in dogs with naturally acquired thoracolumbar spinal cord disease. Am J Vet Res 54:1935–1941

    PubMed  CAS  Google Scholar 

  50. Nollet H, Van Ham L, Deprez P, Vanderstraeten G (2003) Transcranial magnetic stimulation: review of the technique, basic principles and applications. Vet J 166:28–42

    Article  PubMed  CAS  Google Scholar 

  51. Hiersemenzel LP, Curt A, Dietz V (2000) From spinal shock to spasticity: neuronal adaptations to a spinal cord injury. Neurology 54:1574–1582

    Article  PubMed  CAS  Google Scholar 

  52. Shores A, Redding RW, Knecht CD (1987) Spinal-evoked potentials in dogs with acute compressive thoracolumbar spinal cord disease. Am J Vet Res 48:1525–1530

    PubMed  CAS  Google Scholar 

  53. Sylvestre AM, Cockshutt JR, Parent JM, Brooke JD, Holmberg DL, Partlow GD (1993) Magnetic motor evoked potentials for assessing spinal cord integrity in dogs with intervertebral disc disease. Vet Surg 22:5–10

    Article  PubMed  CAS  Google Scholar 

  54. Da Costa RC, Poma R, Parent JM, Partlow G, Monteith G (2006) Correlation of motor evoked potentials with magnetic resonance imaging and neurologic findings in Doberman Pinschers with and without signs of cervical spondylomyelopathy. Am J Vet Res 67:1613–1620

    Article  PubMed  Google Scholar 

  55. Fowler CJ, Griffiths D, De Groat WC (2008) The neural control of micturition. Nat Rev Neurosci 9:453–466

    Article  PubMed  CAS  Google Scholar 

  56. Goldstein RE, Westropp JL (2005) Urodynamic testing in the diagnosis of small animal micturition disorders. Clin Tech Small Anim Pract 20:65–72

    Article  PubMed  Google Scholar 

  57. Biering-Sorensen F, Craggs M, Kennelly M, Schick E, Wyndaele JJ (2008) International lower urinary tract function basic spinal cord injury data set. Spinal Cord 46:325–330

    Article  PubMed  CAS  Google Scholar 

  58. Ho CH, Linsenmeyer TA, Millis SR (2000) The reproducibility of urodynamic studies of neurogenic bladders in spinal cord injury. J Spinal Cord Med 23:276–283

    PubMed  CAS  Google Scholar 

  59. Handa Y, Naito A, Watababe S, Komatsu S, Shimizu Y (1986) Functional recovery of locomotive behavior in the adult spinal dog. Tohoku J Exp Med 148:373–384

    Article  PubMed  CAS  Google Scholar 

  60. Hamilton L, Franklin RJ, Jeffery ND (2007) Development of a universal measure of quadrupedal forelimb-hindlimb coordination using digital motion capture and computerised analysis. BMC Neurosci 8:77

    Article  PubMed  Google Scholar 

  61. Hamilton L, Franklin RJ, Jeffery ND (2008) Quantification of deficits in lateral paw positioning after spinal cord injury in dogs. BMC Vet Res 4:47

    Article  PubMed  Google Scholar 

  62. Blight AR (1983) Cellular morphology of chronic spinal cord injury in the cat: analysis of myelinated axons by line-sampling. Neuroscience 10:521–543

    Article  PubMed  CAS  Google Scholar 

  63. Cohen-Adac J, Benali H, Hoge RD, Rossignol S (2008) In vivo DTI of the healthy and injured cat spinal cord at high spatial and angular resolution. Neuroimage 40:685–697

    Article  Google Scholar 

  64. Yang HW, Lemon RN (2003) An electron microscopic examination of the corticospinal projection to the cervical spinal cord in the rat: lack of evidence for cortico-motoneuronal synapses. Exp Brain Res 149:458–469

    PubMed  Google Scholar 

  65. Borgens RB, Toombs JP, Breur G, Widmer WR, Waters D, Harbath AM et al (1999) An imposed oscillating electrical field improves the recovery of function in neurologically complete paraplegic dogs. J Neurotrauma 16:639–657

    Article  PubMed  CAS  Google Scholar 

  66. Blight AR, Toombs JP, Bauer MS, Widmer WR (1991) The effects of 4-aminopyridine on neurological deficits in chronic cases of traumatic spinal cord injury in dogs: a phase I clinical trial. J Neurotrauma 8:103–119

    Article  PubMed  CAS  Google Scholar 

  67. Baltzer WI, McMichael MA, Hosgood GL, Kerwin SC, Levine JM, Steiner JM et al (2008) Randomized, blinded, placebo-controlled clinical trial of N-acetylcysteine in dogs with spinal cord trauma from acute intervertebral disc disease. Spine (Phila Pa 1976) 33:1397–1402

    Article  Google Scholar 

  68. Olby N (2010) The pathogenesis and treatment of acute spinal cord injuries in dogs. Vet Clin North Am Small Anim Pract 40:791–807

    Article  PubMed  Google Scholar 

  69. Skinner AP, Pachnicke S, Lakatos A, Franklin RJ, Jeffery ND (2005) Nasal and frontal sinus mucosa of the adult dog contain numerous olfactory sensory neurons and ensheathing glia. Res Vet Sci 78:9–15

    Article  PubMed  CAS  Google Scholar 

  70. Bock P, Beineke A, Techangamsuwan S, Baumgartner W, Wetzer K (2007) Differential expression of HNK-1 and p75(NTR) in adult canine Schwann cells and olfactory ensheathing cells in situ but not in vitro. J Comp Neurol 505:572–585

    Article  PubMed  Google Scholar 

  71. Techangamsuwan S, Kreutzer R, Kreutzer M, Imbschweiler I, Rohn K, Wewetzer K et al (2009) Transfection of adult canine Schwann cells and olfactory ensheathing cells at early and late passage with human TERT differentially affects growth factor responsiveness and in vitro growth. J Neurosci Methods 176:112–120

    Article  PubMed  CAS  Google Scholar 

  72. Jeffery ND, Lakatos A, Franklin RJ (2005) Autologous olfactory glial cell transplantation is reliable and safe in naturally occurring canine spinal cord injury. J Neurotrauma 22:1282–1293

    Article  PubMed  Google Scholar 

  73. Woodhouse A, Vincent AJ, Kozel MA, Chung RS, Waite PM, Vickers JC et al (2005) Spinal cord tissue affects ensheathing cell proliferation and apoptosis. Neuroreport 16:737–740

    Article  PubMed  Google Scholar 

  74. Chua SJ, Bielecki R, Yamanaka N, Fehlings MG, Rogers IM, Casper RF (2010) The effect of umbilical cord blood cells on outcomes after experimental traumatic spinal cord injury. Spine (Phila Pa 1976) 35:1520–1526

    Article  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, USA

    Nick D. Jeffery

  2. School of Veterinary Sciences, University of Bristol, Langford, UK

    Nicolas Granger

  3. Department of Veterinary Medicine, University of Cambridge, Cambridge, UK

    Robin J. M. Franklin

Authors
  1. Nick D. Jeffery
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  2. Nicolas Granger
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  3. Robin J. M. Franklin
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Corresponding author

Correspondence to Nick D. Jeffery .

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Editors and Affiliations

  1. Biomedical Center, Department of Neuroscience, Uppsala University, Husargatan 3, Uppsala, 751 24, Sweden

    HÃ¥kan Aldskogius

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Jeffery, N.D., Granger, N., Franklin, R.J.M. (2013). Using Naturally Occurring Spinal Cord Injury in Domestic Dogs to Explore Novel Therapeutic Options. In: Aldskogius, H. (eds) Animal Models of Spinal Cord Repair. Neuromethods, vol 76. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-197-4_9

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  • DOI: https://doi.org/10.1007/978-1-62703-197-4_9

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-196-7

  • Online ISBN: 978-1-62703-197-4

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