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Translation: Relevance of Spinal Cord Injury Animal Models

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Book cover Neurological Aspects of Spinal Cord Injury

Abstract

There are currently no therapeutic interventions available for the treatment of spinal cord injury (SCI). The discovery and validation of the growing number of promising therapies will require continued reliance on preclinical animal models of SCI prior to human translation. Animal models of SCI are instrumental in better understanding the mechanisms involved in traumatic SCI and evaluating the efficacy of therapeutic interventions. Over the past 40 years, substantial gains have been made in developing consistent, reproducible and reliable animal SCI models.

These models vary in terms of the species utilized, injury location, and injury mechanism, each with its own advantages and disadvantages. While the controlled experimental environment of preclinical studies is considered advantageous, it is this that makes animal models distinct from clinical reality, where there is considerable heterogeneity in baseline health and injury mechanics. The challenge then, is to evaluate what level of preclinical evidence is sufficient to proceed with clinical trials.The range of experimental paradigms available to the scientific community give new opportunities to address translational questions prior to human testing. Continued open communication involving scientists, clinicians, regulatory agencies, funding agencies, and the individuals living with SCI is required to move forward efficiently towards the establishment of novel therapeutics for the treatment of SCI.

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References

  1. Aguilar RM, Steward O (2010) A bilateral cervical contusion injury model in mice: assessment of gripping strength as a measure of forelimb motor function. Exp Neurol 221(1):38–53. doi:10.1016/j.expneurol.2009.09.028

    Article  PubMed  Google Scholar 

  2. Akhtar AZ, Pippin JJ, Sandusky CB (2008) Animal models in spinal cord injury: a review. Rev Neurosci 19(1):47–60

    Article  PubMed  Google Scholar 

  3. Allen A (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 LVII 11:878–880. doi:10.1001/jama.1911.04260090100008

    Article  Google Scholar 

  4. Anderson KD (2004) Targeting recovery: priorities of the spinal cord-injured population. J Neurotrauma 21(10):1371–1383

    Article  PubMed  Google Scholar 

  5. Antonic A, Sena ES, Lees JS, Wills TE, Skeers P, Batchelor PE, Macleod MR, Howells DW (2013) Stem cell transplantation in traumatic spinal cord injury: a systematic review and meta-analysis of animal studies. PLoS Biol 11(12), e1001738. doi:10.1371/journal.pbio.1001738

    Article  PubMed  PubMed Central  Google Scholar 

  6. Barbeau H, Rossignol S (1987) Recovery of locomotion after chronic spinalization in the adult cat. Brain Res 412(1):84–95

    Article  CAS  PubMed  Google Scholar 

  7. Basoglu H, Kurtoglu T, Cetin NK, Bilgin MD, Kiylioglu N (2013) Assessment of in vivo spinal cord conduction velocity in rats in an experimental model of ischemic spinal cord injury. Spinal Cord 51(8):616–622. doi:10.1038/sc.2013.40

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  9. Basso DM, Beattie MS, Bresnahan JC, Anderson DK, Faden AI, Gruner JA, Holford TR, Hsu CY, Noble LJ, Nockels R, Perot PL, Salzman SK, Young W (1996) MASCIS evaluation of open field locomotor scores: effects of experience and teamwork on reliability. Multicenter Animal Spinal Cord Injury Study. J Neurotrauma 13(7):343–359

    Article  CAS  PubMed  Google Scholar 

  10. Begley CG, Ellis LM (2012) Drug development: raise standards for preclinical cancer research. Nature 483(7391):531–533. doi:10.1038/483531a

    Article  CAS  PubMed  Google Scholar 

  11. Behrmann DL, Bresnahan JC, Beattie MS (1993) A comparison of YM-14673, U-50488H, and nalmefene after spinal cord injury in the rat. Exp Neurol 119(2):258–267. doi:10.1006/exnr.1993.1028

    Article  CAS  PubMed  Google Scholar 

  12. Blight AR (2000) Animal models of spinal cord injury. Topics in spinal cord injury rehabilitation 6(2):1–13. doi:10.1310/2XNY-A824-UCTF-EN4D

  13. Blight AR, Tuszynski MH (2006) Clinical trials in spinal cord injury. J Neurotrauma 23(3–4):586–593. doi:10.1089/neu.2006.23.586

    Article  PubMed  Google Scholar 

  14. Bottai D, Cigognini D, Madaschi L, Adami R, Nicora E, Menarini M, Di Giulio AM, Gorio A (2010) Embryonic stem cells promote motor recovery and affect inflammatory cell infiltration in spinal cord injured mice. Exp Neurol 223(2):452–463. doi:10.1016/j.expneurol.2010.01.010

    Article  CAS  PubMed  Google Scholar 

  15. Bresnahan JC, Beattie MS, Stokes BT, Conway KM (1991) Three-dimensional computer-assisted analysis of graded contusion lesions in the spinal cord of the rat. J Neurotrauma 8(2):91–101

    Article  CAS  PubMed  Google Scholar 

  16. Bresnahan JC, Beattie MS, Todd FD 3rd, Noyes DH (1987) A behavioral and anatomical analysis of spinal cord injury produced by a feedback-controlled impaction device. Exp Neurol 95(3):548–570

    Article  CAS  PubMed  Google Scholar 

  17. Brock JH, Rosenzweig ES, Blesch A, Moseanko R, Havton LA, Edgerton VR, Tuszynski MH (2010) Local and remote growth factor effects after primate spinal cord injury. J Neurosci 30(29):9728–9737. doi:10.1523/JNEUROSCI.1924-10.2010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Brösamle C, Huber AB (2006) Cracking the black box – and putting it back together again: animal models of spinal cord injury. Drug discovery today: disease models 3(4):341–347. doi:http://dx.doi.org/10.1016/j.ddmod.2006.11.006

  19. Brown TG (1911) The intrinsic factors in the act of progression in the mammal. Proceedings of the Royal Society of London Series B, Containing Papers of a Biological Character 84(572):308–319. doi:10.2307/80647

    Article  Google Scholar 

  20. Burke DA, Whittemore SR, Magnuson DS (2013) Consequences of common data analysis inaccuracies in CNS trauma injury basic research. J Neurotrauma 30(10):797–805. doi:10.1089/neu.2012.2704

    Article  PubMed  PubMed Central  Google Scholar 

  21. Button KS, Ioannidis JP, Mokrysz C, Nosek BA, Flint J, Robinson ES, Munafo MR (2013) Power failure: why small sample size undermines the reliability of neuroscience. Nat Rev Neurosci 14(5):365–376. doi:10.1038/nrn3475

    Article  CAS  PubMed  Google Scholar 

  22. Cohen J (1962) The statistical power of abnormal-social psychological research: a review. J Abnorm Soc Psychol 65:145–153

    Article  CAS  PubMed  Google Scholar 

  23. Cohen J (1994) The earth is round (p < 0.05). Am Psychol 49:997–1003

    Article  Google Scholar 

  24. Dietrich WD (2003) Confirming an experimental therapy prior to transfer to humans: what is the ideal? J Rehabil Res Dev 40(4 Suppl 1):63–69

    Article  PubMed  Google Scholar 

  25. Fawcett JW, Curt A, Steeves JD, Coleman WP, Tuszynski MH, Lammertse D, Bartlett PF, Blight AR, Dietz V, Ditunno J, Dobkin BH, Havton LA, Ellaway PH, Fehlings MG, Privat A, Grossman R, Guest JD, Kleitman N, Nakamura M, Gaviria M, Short D (2007) Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: spontaneous recovery after spinal cord injury and statistical power needed for therapeutic clinical trials. Spinal Cord 45(3):190–205. doi:10.1038/sj.sc.3102007

    Article  CAS  PubMed  Google Scholar 

  26. Fehlings MG, Baptiste DC (2005) Current status of clinical trials for acute spinal cord injury. Injury 36(Suppl 2):B113–B122. doi:10.1016/j.injury.2005.06.022

    Article  PubMed  Google Scholar 

  27. Fehlings MG, Tator CH, Linden RD (1989) The relationships among the severity of spinal cord injury, motor and somatosensory evoked potentials and spinal cord blood flow. Electroencephalogr Clin Neurophysiol 74(4):241–259

    Article  CAS  PubMed  Google Scholar 

  28. Forgione N, Karadimas SK, Foltz WD, Satkunendrarajah K, Lip A, Fehlings MG (2014) Bilateral contusion-compression model of incomplete traumatic cervical spinal cord injury. J Neurotrauma 31(21):1776–1788. doi:10.1089/neu.2014.3388

    Article  PubMed  PubMed Central  Google Scholar 

  29. Frantz S (2012) Embryonic stem cell pioneer Geron exits field, cuts losses. Nat Biotechnol 30(1):12–13. doi:10.1038/nbt0112-12

    Article  CAS  PubMed  Google Scholar 

  30. Gaviria M, Haton H, Sandillon F, Privat A (2002) A mouse model of acute ischemic spinal cord injury. J Neurotrauma 19(2):205–221. doi:10.1089/08977150252806965

    Article  PubMed  Google Scholar 

  31. Geisler FH, Coleman WP, Grieco G, Poonian D, Sygen Study Group (2001) The Sygen multicenter acute spinal cord injury study. Spine 26(24 Suppl):S87–S98

    Article  CAS  PubMed  Google Scholar 

  32. Geisler FH, Dorsey FC, Coleman WP (1991) Recovery of motor function after spinal-cord injury--a randomized, placebo-controlled trial with GM-1 ganglioside. N Engl J Med 324(26):1829–1838. doi:10.1056/NEJM199106273242601

    Article  CAS  PubMed  Google Scholar 

  33. Gonzalez-Lara LE, Xu X, Hofstetrova K, Pniak A, Brown A, Foster PJ (2009) In vivo magnetic resonance imaging of spinal cord injury in the mouse. J Neurotrauma 26(5):753–762. doi:10.1089/neu.2008.0704

    Article  PubMed  Google Scholar 

  34. Granger N, Blamires H, Franklin RJ, Jeffery ND (2012) Autologous olfactory mucosal cell transplants in clinical spinal cord injury: a randomized double-blinded trial in a canine translational model. Brain 135(Pt 11):3227–3237. doi:10.1093/brain/aws268

    Article  PubMed  PubMed Central  Google Scholar 

  35. Gruner JA (1992) A monitored contusion model of spinal cord injury in the rat. J Neurotrauma 9(2):123–126; discussion 126–128

    Article  CAS  PubMed  Google Scholar 

  36. Guizar-Sahagun G, Grijalva I, Hernandez-Godinez B, Franco-Bourland RE, Cruz-Antonio L, Martinez-Cruz A, Ibanez-Contreras A, Madrazo I (2011) New approach for graded compression spinal cord injuries in rhesus macaque: method feasibility and preliminary observations. J Med Primatol 40(6):401–413. doi:10.1111/j.1600-0684.2011.00483.x

    Article  PubMed  Google Scholar 

  37. Hao JX, Xu XJ, Aldskogius H, Seiger A, Wiesenfeld-Hallin Z (1991) Allodynia-like effects in rat after ischaemic spinal cord injury photochemically induced by laser irradiation. Pain 45(2):175–185

    Article  CAS  PubMed  Google Scholar 

  38. Harkema SJ (2001) Neural plasticity after human spinal cord injury: application of locomotor training to the rehabilitation of walking. Neuroscientist 7(5):455–468

    Article  CAS  PubMed  Google Scholar 

  39. Inada T, Yamanouchi Y, Jomura S, Sakamoto S, Takahashi M, Kambara T, Shingu K (2004) Effect of propofol and isoflurane anaesthesia on the immune response to surgery. Anaesthesia 59(10):954–959. doi:10.1111/j.1365-2044.2004.03837.x

    Article  CAS  PubMed  Google Scholar 

  40. Inoue T, Lin A, Ma X, McKenna SL, Creasey GH, Manley GT, Ferguson AR, Bresnahan JC, Beattie MS (2013) Combined SCI and TBI: recovery of forelimb function after unilateral cervical spinal cord injury (SCI) is retarded by contralateral traumatic brain injury (TBI), and ipsilateral TBI balances the effects of SCI on paw placement. Exp Neurol 248:136–147. doi:10.1016/j.expneurol.2013.06.006

    Article  PubMed  PubMed Central  Google Scholar 

  41. Ishimaru M, Fukamauchi F, Olney JW (1995) Halothane prevents MK-801 neurotoxicity in the rat cingulate cortex. Neurosci Lett 193(1):1–4

    Article  CAS  PubMed  Google Scholar 

  42. Iwanami A, Kaneko S, Nakamura M, Kanemura Y, Mori H, Kobayashi S, Yamasaki M, Momoshima S, Ishii H, Ando K, Tanioka Y, Tamaoki N, Nomura T, Toyama Y, Okano H (2005) Transplantation of human neural stem cells for spinal cord injury in primates. J Neurosci Res 80(2):182–190. doi:10.1002/jnr.20436

    Article  CAS  PubMed  Google Scholar 

  43. Jakeman LB, Guan Z, Wei P, Ponnappan R, Dzwonczyk R, Popovich PG, Stokes BT (2000) Traumatic spinal cord injury produced by controlled contusion in mouse. J Neurotrauma 17(4):299–319

    Article  CAS  PubMed  Google Scholar 

  44. 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(10):584–593. doi:10.1038/sj.sc.3101912

    Article  CAS  PubMed  Google Scholar 

  45. Johnson VE (2013) Revised standards for statistical evidence. Proc Natl Acad Sci U S A 110(48):19313–19317. doi:10.1073/pnas.1313476110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Kawaguchi M, Furuya H, Patel PM (2005) Neuroprotective effects of anesthetic agents. J Anesth 19(2):150–156. doi:10.1007/s00540-005-0305-5

    Article  PubMed  Google Scholar 

  47. Keomani E, Deramaudt TB, Petitjean M, Bonay M, Lofaso F, Vinit S (2014) A murine model of cervical spinal cord injury to study post-lesional respiratory neuroplasticity. J Vis Exp (87). doi:10.3791/51235

  48. Kunkel-Bagden E, Dai HN, Bregman BS (1993) Methods to assess the development and recovery of locomotor function after spinal cord injury in rats. Exp Neurol 119(2):153–164. doi:10.1006/exnr.1993.1017

    Article  CAS  PubMed  Google Scholar 

  49. Kwon BK, Ghag A, Dvorak MF, Tetzlaff W, Illes J (2012) Expectations of benefit and tolerance to risk of individuals with spinal cord injury regarding potential participation in clinical trials. J Neurotrauma 29(18):2727–2737. doi:10.1089/neu.2012.2550

    Article  PubMed  Google Scholar 

  50. Kwon BK, Ghag A, Reichl L, Dvorak MF, Illes J, Tetzlaff W (2012) Opinions on the preclinical evaluation of novel therapies for spinal cord injury: a comparison between researchers and spinal cord-injured individuals. J Neurotrauma 29(14):2367–2374. doi:10.1089/neu.2012.2479

    Article  PubMed  Google Scholar 

  51. Kwon BK, Hillyer J, Tetzlaff W (2010) Translational research in spinal cord injury: a survey of opinion from the SCI community. J Neurotrauma 27(1):21–33. doi:10.1089/neu.2009.1048

    Article  PubMed  Google Scholar 

  52. Kwon BK, Okon E, Hillyer J, Mann C, Baptiste D, Weaver LC, Fehlings MG, Tetzlaff W (2011) A systematic review of non-invasive pharmacologic neuroprotective treatments for acute spinal cord injury. J Neurotrauma 28(8):1545–1588. doi:10.1089/neu.2009.1149

    Article  PubMed  PubMed Central  Google Scholar 

  53. Kwon BK, Okon EB, Tsai E, Beattie MS, Bresnahan JC, Magnuson DK, Reier PJ, McTigue DM, Popovich PG, Blight AR, Oudega M, Guest JD, Weaver LC, Fehlings MG, Tetzlaff W (2011) 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(8):1525–1543. doi:10.1089/neu.2010.1296

    Article  PubMed  PubMed Central  Google Scholar 

  54. Kwon BK, Soril LJ, Bacon M, Beattie MS, Blesch A, Bresnahan JC, Bunge MB, Dunlop SA, Fehlings MG, Ferguson AR, Hill CE, Karimi-Abdolrezaee S, Lu P, McDonald JW, Muller HW, Oudega M, Rosenzweig ES, Reier PJ, Silver J, Sykova E, Xu XM, Guest JD, Tetzlaff W (2013) Demonstrating efficacy in preclinical studies of cellular therapies for spinal cord injury - how much is enough? Exp Neurol 248:30–44. doi:10.1016/j.expneurol.2013.05.012

    Article  PubMed  Google Scholar 

  55. Kwon BK, Streijger F, Hill CE, Anderson AJ, Bacon M, Beattie MS, Blesch A, Bradbury EJ, Brown A, Bresnahan JC, Case CC, Colburn RW, David S, Fawcett JW, Ferguson AR, Fischer I, Floyd CL, Gensel JC, Houle JD, Jakeman LB, Jeffery ND, Jones LA, Kleitman N, Kocsis J, Lu P, Magnuson DS, Marsala M, Moore SW, Mothe AJ, Oudega M, Plant GW, Rabchevsky AS, Schwab JM, Silver J, Steward O, Xu XM, Guest JD, Tetzlaff W (2015) Large animal and primate models of spinal cord injury for the testing of novel therapies. Exp Neurol 269:154–168. doi:10.1016/j.expneurol.2015.04.008

    Article  PubMed  Google Scholar 

  56. Lammertse D, Tuszynski MH, Steeves JD, Curt A, Fawcett JW, Rask C, Ditunno JF, Fehlings MG, Guest JD, Ellaway PH, Kleitman N, Blight AR, Dobkin BH, Grossman R, Katoh H, Privat A, Kalichman M, International Campaign for Cures of Spinal Cord Injury Paralysis (2007) Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: clinical trial design. Spinal Cord 45(3):232–242. doi:10.1038/sj.sc.3102010

    Article  CAS  PubMed  Google Scholar 

  57. Lammertse DP (2004) Update on pharmaceutical trials in acute spinal cord injury. J Spinal Cord Med 27(4):319–325

    Article  PubMed  Google Scholar 

  58. Lazic SE, Essioux L (2013) Improving basic and translational science by accounting for litter-to-litter variation in animal models. BMC Neurosci 14:37. doi:10.1186/1471-2202-14-37

    Article  PubMed  PubMed Central  Google Scholar 

  59. Lee JH, Choi CB, Chung DJ, Kang EH, Chang HS, Hwang SH, Han H, Choe BY, Sur JH, Lee SY, Kim HY (2008) Development of an improved canine model of percutaneous spinal cord compression injury by balloon catheter. J Neurosci Methods 167(2):310–316. doi:10.1016/j.jneumeth.2007.07.020

    Article  PubMed  Google Scholar 

  60. Lee JH, Jones CF, Okon EB, Anderson L, Tigchelaar S, Kooner P, Godbey T, Chua B, Gray G, Hildebrandt R, Cripton P, Tetzlaff W, Kwon BK (2013) A novel porcine model of traumatic thoracic spinal cord injury. J Neurotrauma 30(3):142–159. doi:10.1089/neu.2012.2386

    Article  PubMed  Google Scholar 

  61. Lee JH, Roy J, Sohn HM, Cheong M, Liu J, Stammers AT, Tetzlaff W, Kwon BK (2010) Magnesium in a polyethylene glycol formulation provides neuroprotection after unilateral cervical spinal cord injury. Spine (Phila Pa 1976) 35(23):2041–2048. doi:10.1097/BRS.0b013e3181d2d6c5

    Article  Google Scholar 

  62. Lee JH, Streijger F, Tigchelaar S, Maloon M, Liu J, Tetzlaff W, Kwon BK (2012) A contusive model of unilateral cervical spinal cord injury using the infinite horizon impactor. J Vis Exp (65). doi:10.3791/3313

  63. Lee JH, Tigchelaar S, Liu J, Stammers AM, Streijger F, Tetzlaff W, Kwon BK (2010) Lack of neuroprotective effects of simvastatin and minocycline in a model of cervical spinal cord injury. Exp Neurol 225(1):219–230. doi:10.1016/j.expneurol.2010.06.018

    Article  CAS  PubMed  Google Scholar 

  64. Leem YJ, Joh JW, Joeng KW, Suh JH, Shin JW, Leem JG (2010) Central pain from excitotoxic spinal cord injury induced by intraspinal NMDA injection: a pilot study. Korean J Pain 23(2):109–115. doi:10.3344/kjp.2010.23.2.109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Lemmon VP, Ferguson AR, Popovich PG, Xu XM, Snow DM, Igarashi M, Beattie CE, Bixby JL, MIASCI Consortium (2014) Minimum information about a spinal cord injury experiment: a proposed reporting standard for spinal cord injury experiments. J Neurotrauma 31(15):1354–1361. doi:10.1089/neu.2014.3400

    Article  PubMed  PubMed Central  Google Scholar 

  66. Levine JM, Levine GJ, Porter BF, Topp K, Noble-Haeusslein LJ (2011) Naturally occurring disk herniation in dogs: an opportunity for pre-clinical spinal cord injury research. J Neurotrauma 28(4):675–688. doi:10.1089/neu.2010.1645

    Article  PubMed  PubMed Central  Google Scholar 

  67. Lim JH, Jung CS, Byeon YE, Kim WH, Yoon JH, Kang KS, Kweon OK (2007) Establishment of a canine spinal cord injury model induced by epidural balloon compression. J Vet Sci 8(1):89–94

    Article  PubMed  PubMed Central  Google Scholar 

  68. Lovely RG, Gregor RJ, Roy RR, Edgerton VR (1986) Effects of training on the recovery of full-weight-bearing stepping in the adult spinal cat. Exp Neurol 92(2):421–435

    Article  CAS  PubMed  Google Scholar 

  69. Mondello SE, Sunshine MD, Fischedick AE, Moritz CT, Horner PJ (2015) A cervical hemi-contusion spinal cord injury model for the investigation of novel therapeutics targeting proximal and distal forelimb functional recovery. J Neurotrauma. doi:10.1089/neu.2014.3792

    PubMed Central  Google Scholar 

  70. Moon ES, Karadimas SK, Yu WR, Austin JW, Fehlings MG (2014) Riluzole attenuates neuropathic pain and enhances functional recovery in a rodent model of cervical spondylotic myelopathy. Neurobiol Dis 62:394–406. doi:10.1016/j.nbd.2013.10.020

    Article  CAS  PubMed  Google Scholar 

  71. Nakae A, Nakai K, Yano K, Hosokawa K, Shibata M, Mashimo T (2011) The animal model of spinal cord injury as an experimental pain model. J Biomed Biotechnol 2011:939023. doi:10.1155/2011/939023

    Article  PubMed  PubMed Central  Google Scholar 

  72. Navarro R, Juhas S, Keshavarzi S, Juhasova J, Motlik J, Johe K, Marsala S, Scadeng M, Lazar P, Tomori Z, Schulteis G, Beattie M, Ciacci JD, Marsala M (2012) Chronic spinal compression model in minipigs: a systematic behavioral, qualitative, and quantitative neuropathological study. J Neurotrauma 29(3):499–513. doi:10.1089/neu.2011.2076

    Article  PubMed  PubMed Central  Google Scholar 

  73. Nieuwenhuis S, Forstmann BU, Wagenmakers EJ (2011) Erroneous analyses of interactions in neuroscience: a problem of significance. Nat Neurosci 14(9):1105–1107. doi:10.1038/nn.2886

    Article  CAS  PubMed  Google Scholar 

  74. Noble M, Mayer-Proschel M, Davies JE, Davies SJ, Proschel C (2011) Cell therapies for the central nervous system: how do we identify the best candidates? Curr Opin Neurol 24(6):570–576. doi:10.1097/WCO.0b013e32834cd4c9

    Article  PubMed  Google Scholar 

  75. Nobunaga AI, Go BK, Karunas RB (1999) Recent demographic and injury trends in people served by the Model Spinal Cord Injury Care Systems. Arch Phys Med Rehabil 80(11):1372–1382

    Article  CAS  PubMed  Google Scholar 

  76. Nout YS, Rosenzweig ES, Brock JH, Strand SC, Moseanko R, Hawbecker S, Zdunowski S, Nielson JL, Roy RR, Courtine G, Ferguson AR, Edgerton VR, Beattie MS, Bresnahan JC, Tuszynski MH (2012) Animal models of neurologic disorders: a nonhuman primate model of spinal cord injury. Neurotherapeutics 9(2):380–392. doi:10.1007/s13311-012-0114-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Panjabi MM, Kifune M, Wen L, Arand M, Oxland TR, Lin RM, Yoon WS, Vasavada A (1995) Dynamic canal encroachment during thoracolumbar burst fractures. J Spinal Disord 8(1):39–48

    Article  CAS  PubMed  Google Scholar 

  78. Poon PC, Gupta D, Shoichet MS, Tator CH (2007) Clip compression model is useful for thoracic spinal cord injuries: histologic and functional correlates. Spine (Phila Pa 1976) 32(25):2853–2859. doi:10.1097/BRS.0b013e31815b7e6b

    Article  Google Scholar 

  79. Prinz F, Schlange T, Asadullah K (2011) Believe it or not: how much can we rely on published data on potential drug targets? Nat Rev Drug Discov 10(9):712. doi:10.1038/nrd3439-c1

    Article  CAS  PubMed  Google Scholar 

  80. Rahimi-Movaghar V, Yazdi A, Karimi M, Mohammadi M, Firouzi M, Zanjani LO, Nabian MH (2008) Effect of decompression on complete spinal cord injury in rats. Int J Neurosci 118(10):1359–1373. doi:10.1080/00207450701392340

    Article  PubMed  Google Scholar 

  81. Ramer LM, Ramer MS, Bradbury EJ (2014) Restoring function after spinal cord injury: towards clinical translation of experimental strategies. Lancet Neurol 13(12):1241–1256. doi:10.1016/S1474-4422(14)70144-9

    Article  PubMed  Google Scholar 

  82. Ramer MS, Harper GP, Bradbury EJ (2000) Progress in spinal cord research – a refined strategy for the international spinal research trust. Spinal Cord 38(8):449–472

    Article  CAS  PubMed  Google Scholar 

  83. Rivlin AS, Tator CH (1978) Effect of duration of acute spinal cord compression in a new acute cord injury model in the rat. Surg Neurol 10(1):38–43

    CAS  PubMed  Google Scholar 

  84. Scheff SW, Rabchevsky AG, Fugaccia I, Main JA, Lumpp JE Jr (2003) Experimental modeling of spinal cord injury: characterization of a force-defined injury device. J Neurotrauma 20(2):179–193. doi:10.1089/08977150360547099

    Article  PubMed  Google Scholar 

  85. Simard JM, Tsymbalyuk O, Keledjian K, Ivanov A, Ivanova S, Gerzanich V (2012) Comparative effects of glibenclamide and riluzole in a rat model of severe cervical spinal cord injury. Exp Neurol 233(1):566–574. doi:10.1016/j.expneurol.2011.11.044

    Article  CAS  PubMed  Google Scholar 

  86. Simmons D (2008) The use of animal models in studying genetic disease: transgenesis and induced mutation. Nature education 1(1):70

    Google Scholar 

  87. Steeves JD, Lammertse D, Curt A, Fawcett JW, Tuszynski MH, Ditunno JF, Ellaway PH, Fehlings MG, Guest JD, Kleitman N, Bartlett PF, Blight AR, Dietz V, Dobkin BH, Grossman R, Short D, Nakamura M, Coleman WP, Gaviria M, Privat A, International Campaign for Cures of Spinal Cord Injury Paralysis (2007) Guidelines for the conduct of clinical trials for spinal cord injury (SCI) as developed by the ICCP panel: clinical trial outcome measures. Spinal Cord 45(3):206–221. doi:10.1038/sj.sc.3102008

    Article  CAS  PubMed  Google Scholar 

  88. Sterling TD (1959) Publication decisions and their possible effects on inferences drawn from tests of significance—or vice versa. J Am Stat Assoc 54(285):30–34

    Google Scholar 

  89. Steward O, Popovich PG, Dietrich WD, Kleitman N (2012) Replication and reproducibility in spinal cord injury research. Exp Neurol 233(2):597–605. doi:10.1016/j.expneurol.2011.06.017

    Article  PubMed  Google Scholar 

  90. 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):1–8. doi:10.1002/cne.10593

    Article  PubMed  Google Scholar 

  91. Stokes BT, Noyes DH, Behrmann DL (1992) An electromechanical spinal injury technique with dynamic sensitivity. J Neurotrauma 9(3):187–195

    Article  CAS  PubMed  Google Scholar 

  92. Streijger F, Beernink TM, Lee JH, Bhatnagar T, Park S, Kwon BK, Tetzlaff W (2013) Characterization of a cervical spinal cord hemicontusion injury in mice using the infinite horizon impactor. J Neurotrauma 30(10):869–883. doi:10.1089/neu.2012.2405

    Article  PubMed  Google Scholar 

  93. Streijger F, Plunet WT, Lee JH, Liu J, Lam CK, Park S, Hilton BJ, Fransen BL, Matheson KA, Assinck P, Kwon BK, Tetzlaff W (2013) Ketogenic diet improves forelimb motor function after spinal cord injury in rodents. PLoS One 8(11), e78765. doi:10.1371/journal.pone.0078765

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Talac R, Friedman JA, Moore MJ, Lu L, Jabbari E, Windebank AJ, Currier BL, Yaszemski MJ (2004) Animal models of spinal cord injury for evaluation of tissue engineering treatment strategies. Biomaterials 25(9):1505–1510

    Article  CAS  PubMed  Google Scholar 

  95. Taoka Y, Okajima K (1998) Spinal cord injury in the rat. Prog Neurobiol 56(3):341–358

    Article  CAS  PubMed  Google Scholar 

  96. 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(6):813–819

    Article  CAS  PubMed  Google Scholar 

  97. Tator CH (2006) Review of treatment trials in human spinal cord injury: issues, difficulties, and recommendations. Neurosurgery 59(5):957–982. doi:10.1227/01.NEU.0000245591.16087.89; discussion 982–957

    Article  PubMed  Google Scholar 

  98. Tuszynski MH, Steeves JD, Fawcett JW, Lammertse D, Kalichman M, Rask C, Curt A, Ditunno JF, Fehlings MG, Guest JD, Ellaway PH, Kleitman N, Bartlett PF, Blight AR, Dietz V, Dobkin BH, Grossman R, Privat A, International Campaign for Cures of Spinal Cord Injury Paralysis (2007) Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP Panel: clinical trial inclusion/exclusion criteria and ethics. Spinal Cord 45(3):222–231. doi:10.1038/sj.sc.3102009

    Article  CAS  PubMed  Google Scholar 

  99. van Gorp S, Leerink M, Kakinohana O, Platoshyn O, Santucci C, Galik J, Joosten EA, Hruska-Plochan M, Goldberg D, Marsala S, Johe K, Ciacci JD, Marsala M (2013) Amelioration of motor/sensory dysfunction and spasticity in a rat model of acute lumbar spinal cord injury by human neural stem cell transplantation. Stem Cell Res Ther 4(3):57. doi:10.1186/scrt209

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  100. Vijayaprakash KM, Sridharan N (2013) An experimental spinal cord injury rat model using customized impact device: a cost-effective approach. J Pharmacol Pharmacother 4(3):211–213. doi:10.4103/0976-500X.114607

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Watson BD, Prado R, Dietrich WD, Ginsberg MD, Green BA (1986) Photochemically induced spinal cord injury in the rat. Brain Res 367(1–2):296–300

    Article  CAS  PubMed  Google Scholar 

  102. Watzlawick R, Sena ES, Dirnagl U, Brommer B, Kopp MA, Macleod MR, Howells DW, Schwab JM (2014) Effect and reporting bias of RhoA/ROCK-blockade intervention on locomotor recovery after spinal cord injury: a systematic review and meta-analysis. JAMA Neurol 71(1):91–99. doi:10.1001/jamaneurol.2013.4684

    Article  PubMed  Google Scholar 

  103. Weishaupt N, Vavrek R, Fouad K (2013) Training following unilateral cervical spinal cord injury in rats affects the contralesional forelimb. Neurosci Lett 539:77–81. doi:10.1016/j.neulet.2013.01.043

    Article  CAS  PubMed  Google Scholar 

  104. Wilcox RK, Boerger TO, Hall RM, Barton DC, Limb D, Dickson RA (2002) Measurement of canal occlusion during the thoracolumbar burst fracture process. J Biomech 35(3):381–384

    Article  CAS  PubMed  Google Scholar 

  105. Wrathall JR, Pettegrew RK, Harvey F (1985) Spinal cord contusion in the rat: production of graded, reproducible, injury groups. Exp Neurol 88(1):108–122

    Article  CAS  PubMed  Google Scholar 

  106. Yezierski RP, Liu S, Ruenes GL, Kajander KJ, Brewer KL (1998) Excitotoxic spinal cord injury: behavioral and morphological characteristics of a central pain model. Pain 75(1):141–155

    Article  CAS  PubMed  Google Scholar 

  107. Zhang N, Fang M, Chen H, Gou F, Ding M (2014) Evaluation of spinal cord injury animal models. Neural Regen Res 9(22):2008–2012. doi:10.4103/1673-5374.143436

    PubMed  PubMed Central  Google Scholar 

  108. Zurita M, Aguayo C, Bonilla C, Otero L, Rico M, Rodriguez A, Vaquero J (2012) The pig model of chronic paraplegia: a challenge for experimental studies in spinal cord injury. Prog Neurobiol 97(3):288–303. doi:10.1016/j.pneurobio.2012.04.005

    Article  PubMed  Google Scholar 

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Correspondence to Brian K. Kwon MD, PhD, FRCSC .

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Tigchelaar, S., Kwon, B.K. (2017). Translation: Relevance of Spinal Cord Injury Animal Models. In: Weidner, N., Rupp, R., Tansey, K. (eds) Neurological Aspects of Spinal Cord Injury. Springer, Cham. https://doi.org/10.1007/978-3-319-46293-6_25

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