In vivo and in vitro models of traumatic injuries of the spinal cord

Home/2017, Vol. 5, No. 1/In vivo and in vitro models of traumatic injuries of the spinal cord

Cell and Organ Transplantology. 2017; 5(1):87-93.
DOI: 10.22494/COT.V5I1.71

In vivo and in vitro models of traumatic injuries of the spinal cord

Rybachuk O. A.1,2, Arkhypchuk I. V.1,3, Lazarenko Yu. A.1,4
1Bogomoletz Institute of Physiology NAS of Ukraine, Kyiv, Ukraine
2State Institute of Genetic and Regenerative Medicine NAMS, Kyiv, Ukraine
3Educational and Scientific Center Institute of Biology and Medicine Taras Shevchenko National University, Kyiv, Ukraine
4National University “Kyiv-Mohyla Academy”, Kyiv, Ukraine

In recent years, there is a growing interest in the mechanisms of regeneration of damaged nerve tissue, including the spinal cord, as its injuries are quite common due to traffic accidents, industrial injuries and military actions. Damage to the spinal cord results in the loss of functional activity of the body below the injury site, which affects person’s ability to self-service and significantly reduces its efficiency. The effects of spinal injuries annually cause significant social and economic losses worldwide, including Ukraine. The development of new treatments for pathologies of the central nervous system requires mandatory pre-testing of their effectiveness in experiments in vitro and in vivo. Therefore, searching and creation of optimal animal model of spinal cord injury is in order to it meets most complete picture of the damage characteristic of real conditions in humans. This is an important task of modern neurophysiology. Such models can be used, primarily, for a more detailed clarification of the pathogenesis of all levels of nerve tissue damage and research of its own recovery potential by endogenous reparation mechanisms. In addition, experimental models allow to estimate the safety and predict the effectiveness of various therapeutic approaches to spinal cord injury.

Key words: spinal cord injury; neural tissue injury modelling; glial scar; regeneration

Full Text PDF (eng) Full Text PDF (ua)

1. Holovatsky AS, Cherkasov V, Sapin MR, et al. Anatomіja ljudini u tr’oh tomah [Human Anatomy in three volumes]. Vinnitsa: Nova Kniga – Vinnitsa: New Book, 2007. 456 p. [In Ukrainian].
2. Marunenko IM, Nevedomska YO, Volkovska GI. Anatomіja, fіzіologіja, evoljucіja nervovoї sistemi [Anatomy, physiology, evolution of the nervous system]. Kiїv: «Centr uchbovoї lіteraturi» – Кyiv: “Center of educational literature”, 2013. 184 p. [in Ukrainian]
3. Dunham K, Siriphorn A, Chompoopong S, et al. Characterization of a graded cervical hemicontusion spinal cord injury model in adult male rats. J Neurotrauma. 2010; 27(11): 2091-106. PMid:21087156 PMCid:PMC2978055
4. Griffiths IR. Vasogenic edema following acute and chronic spinal cord compression in the dog. J Neurosurg. 1975; 42(2): 155-165. PMid:1113150
5. Koyanagi I, Tator CH, Theriault E. Silicone rubber microangiography of acute spinal cord injury in the rat. Neurosurgery. 1993; 32(2): 260-68. PMid:8437664
6. Tatagiba M, Brösamle C, Schwab ME. Regeneration of injured axons in the adult mammalian central nervous system. Neurosurgery. 1997; 40(3): 546-47.
8. Brodkey JS, Richards DE, Blasingame JP, et al. Reversible spinal cord trauma in cats. Additive effects of direct pressure and ischemia. J Neurosurg. 1972; 37(5): 591-93. PMid:5076377
9. Chen A, Xu XM, Kleitman N, et al. Methylprednisolone administration improves axonal regeneration into Schwann cell grafts in transected adult rat thoracic spinal cord. Exp Neurol. 1996; 138(2): 261-76. PMid:8620925
10. Fawcett JW. Spinal cord repair: from experimental models to human application. Spinal Cord. 1998; 36(12): 811-17. PMid:9881728
11. Tsymbaliuk VI, Medvediev VV. Spinnoy mozg. Elegiya nadezhdy: monografiya [Spinal cord. Elegy of hope: a monograph]. Vinnitsa: Nova Kniga – Vinnitsa: New Book, 2010. 944 p. [in Russian]
12. Hulsebosch CE. Recent advances in pathophysiology and treatment of spinal cord injury. Adv Physiol Educ. 2002; 26(1-4): 238-55. PMid:12443996
13. Carmel JB, Galante A, Soteropoulos P, et al. Gene expression profiling of acute spinal cord injury reveals spreading inflammatory signals and neuron loss. Physiol Genomics. 2001; 7(2): 201-13. PMid:11773606
14. Bloom O. Non-mammalian model systems for studying neuro-immune interactions after spinal cord injury. Exp Neurol. 2014; 0: 113-30.
15. Ankarcrona M, Dypbukt J, Bonfoco E, et al.Glutamate-induced neuronal death: a succession of necrosis or apoptosis depending on mitochondrial function. Neuron. 1995; 15: 961-73.
16. Sairanen T, Karjalainen-Lindsberg ML, Paetau A, et al. Apoptosis dominant in the periinfarct area of human ischemic stroke – a possible target of antiapoptotic treatments. Brain. 2006; 129(1): 189-99. PMid:16272167
17. Yuan J. Neuroprotective strategies targeting apoptotic and necrotic cell death for stroke. Apoptosis. 2009; 14(4): 469-77. PMid:19137430 PMCid:PMC2745337
18. Wang X, Li Y, Gao Y, et al. Combined use of spinal cord-mimicking partition type scaffold architecture and neurotrophin-3 for surgical repair of completely transected spinal cord in rats. J Biomater Sci Polym Ed. 2013; 24(8): 927-39. PMid:23647249
19. Zeng X, Ma Y, Chen Y, et al. Autocrine fibronectin from differentiating mesenchymal stem cells induces the neurite elongation in vitro and promotes nerve fiber regeneration in transected spinal cord injury. J Biomed Mater Res A. 2016; 104(8): 1902-911. PMid:26991461 PMCid:PMC5101622
20. Khankan R, Griffis K, Haggerty-Skeans J, et al. Olfactory Ensheathing Cell Transplantation after a Complete Spinal Cord Transection Mediates Neuroprotective and Immunomodulatory Mechanisms to Facilitate Regeneration. J Neurosci. 2016; 36(23): 6269-286. PMid:27277804 PMCid:PMC4899528
21. Takiguchi M, Atobe Y, Kadota T, et al. Compensatory projections of primary sensory fibers in lumbar spinal cord after neonatal thoracic spinal transection in rats. Neuroscience. 2015; 304: 349-54. PMid:26208841
22. DePaul M, Lin C, Silver J, et al. Peripheral Nerve Transplantation Combined with Acidic Fibroblast Growth Factor and Chondroitinase Induces Regeneration and Improves Urinary Function in Complete Spinal Cord Transected Adult Mice. PLoS One. 2015; 10(10): 1-16. PMid:26426529 PMCid:PMC4591338
23. Wada N, Shimizu T, Takai S, et al. Post-injury bladder management strategy in fl uences lower urinary tract dysfunction in the mouse model of spinal cord injury. Neurourol Urodynam. 2016. Available:
24. Oda Y, Tani K, Asari Y, et al. Canine Bone Marrow Stromal Cells Promote Functional Recovery in Mice with Spinal Cord Injury. J Vet Med Sci. 2014; 76(6): 905-908. PMid:24561315 PMCid:PMC4108777
25. Han S, Wang B, Li X, et al. Bone marrow-derived mesenchymal stem cells in three-dimensional culture promote neuronal regeneration by neurotrophic protection and immunomodulation. J Biomed Mater Res A. 2016; 104(7): 1759-769. PMid:26990583
26. Rao J, Yang Y, Lin S, et al. Repair of spinal cord injury by chitosan scaffold with glioma ECM and SB216763 implantation in adult rats. J Biomed Mater Res A. 2015; 103(10): 3259-272. PMid:25809817
27. Kanno H, Ozawa H, Tateda S, et al. Upregulation of the receptor-interacting protein 3 expression and involvement in neural tissue damage after spinal cord injury in mice. BMC Neurosci. 2015; 16(62): 1-10.
28. Do-Thi A, Perrin F, Desclaux M, et al. Combination of grafted Schwann cells and lentiviral-mediated prevention of glial scar formation improve recovery of spinal cord injured rats. J Chem Neuroanat. 2016; 76: 48-60. PMid:26744118
29. Xiao W, Yu A, Liu D, et al. Ligustilide treatment promotes functional recovery in a rat model of spinal cord injury via preventing ROS production. Int J Clin Exp Pathol. 2015; 8(10): 12005-12013. PMid:26722386 PMCid:PMC4680331
30. Tsymbaliuk V, Medvediev V, Rybachuk O, et al. The Effect of Implantation of Neurogeltm Used with Xenogenic Bone Marrow Stem Cells on Motor Function Recovery after Experimental Spinal Cord Injury. Int Neurol J. 2016; 84(6): 13-19.
31. Tsymbaliuk V, Medvediev V, Semenova V, et al. Clinical and pathomorphological features of penetrating spinal cord injury model with prolonged persistence of a foreign body in the vertebral canal. Ukr Neurosurg J. 2016; 4: 16-25.
32. Tsymbaliuk V, Medvediev V, Semenova V, et al. The model of lateral spinal cord hemisection. Part I. The technical, pathomorphological, clinical and experimental peculiarities. Ukr Neurosurg J. 2016; 7: 18-27.
33. Albadawi H, Chen J, Oklu R, et al. Spinal Cord Inflammation: Molecular Imaging after Thoracic Aortic Ischemia Reperfusion Injury. Radiology. 2017; 282(1): 202-211. PMid:27509542
34. Nguyen B, Albadawi H, Oklu R, et al. Ethyl pyruvate modulates delayed paralysis following thoracic aortic ischemia reperfusion in mice. J Vasc Surg. 2016; 64(5): 1433-443. PMid:27776698
35. Bell M, Puskas F, Bennett D, et al. Clinical indicators of paraplegia underplay universal spinal cord neuronal injury from transient aortic occlusion. Brain Res. 2015. Available:
36. Li H, Choudhury G, Zhang N, et al. Photothrombosis-induced focal ischemia as a model of spinal cord injury in mice. J Vis Exp. 2015. Available:
37. Batista C, Bianqui L, Zanon B, et al. Behavioral improvement and regulation of molecules related to neuroplasticity in ischemic rat spinal cord treated with PEDF. Neural Plast. 2014. Available:
38. Piao M, Lee J, Jang J, et al. Melatonin improves functional outcome via inhibition of matrix metalloproteinases-9 after photothrombotic spinal cord injury in rats. Acta Neurochir. (Wien). 2014; 156(11): 2173-182. PMid:24879621
39. Farahabadi A, Akbari M, Pishva A, et al. Effect of Progesterone Therapy on TNF-α and iNOS Gene Expression in Spinal Cord Injury Model. Acta Med Iran. 2016; 54(6): 345-51. PMid:27306339
40. Fan H, Chen K, Duan L, et al. Beneficial effects of early hemostasis on spinal cord injury in the rat. Spinal Cord. 2016; 54(11): 924-32.
41. Aydin H, Ozkara E, Ozbek Z, et al. Histopathological evaluation of the effects of CAPE in experimental spinal cord injury. Turk Neurosurg. 2016; 26(3): 437-44. PMid:27161473
42. Wu J, Maoqiang L, Fan H, et al. Rutin attenuates neuroinflammation in spinal cord injury rats. J Surg Res. 2016; 203(2): 331-37. PMid:27363641
43. Farsi L, Afshari K, Keshavarz M, et al. Postinjury treatment with magnesium sulfate attenuates neuropathic pains following spinal cord injury in male rats. Behav Pharmacol. 2015; 26(3): 315-20. PMid:25369748
44. Ruzicka J, Machova-Urdzikova L, Gillick J, et al. A comparative study of three different types of stem cells for treatment of rat spinal cord injury. Cell Transplant. 2016; 1(914): 1-51.
45. Vanický I, Urdzíková L, Saganová K, et al. A simple and reproducible model of spinal cord injury induced by epidural balloon inflation in the rat. J Neurotrauma. 2001; 18(12): 1399-407. PMid:11780869
46. Morris S, Howard J, Rasmusson D, et al. Validity of Transcranial Motor Evoked Potentials as Early Indicators of Neural Compromise in Rat Model of Spinal Cord Compression. Spine. 2015; 40(8): 492-497. PMid:25868103
47. Rosene F, Raul M, Bressan B, et al. Transplantation of Human Skin-Derived Mesenchymal Stromal Cells Improves Locomotor Recovery After Spinal Cord Injury in Rats. Cell Mol Neurobiol. 2016. Available:
48. Allen AR. Surgery of experimental lesion of spinal cord an equivalent to crush injury of fracture dislocation of spinal column Preliminary Report. JAMA. 1911; 57: 878-80.
49. Keller AV, Wainwright G, Shum-Siu A, et al. Disruption of locomotion in response to hindlimb muscle stretch at acute and chronic time points after a spinal cord injury in rats. J Neurotrauma. 2017; 34(3): 661-70. PMid:27196003
50. Caudle KL, Atkinson DA, Brown EH, et al. Hindlimb Stretching Alters Locomotor Function After Spinal Cord Injury in the Adult Rat. Neurorehabil Neural Repair. 2015; 29(3): 268-77. PMid:25106555 PMCid:PMC4312740
51. Zhang S, Huang F, Gates M, et al. Early application of tail nerve electrical stimulation-induced walking training promotes locomotor recovery in rats with spinal cord injury. Spinal Cord. 2016; 54(11): 942-46. PMid:27067652 PMCid:PMC5399155
52. Magnuson DS, Trinder TC, Zhang YP, et al. Comparing deficits following excitotoxic and contusion injuries in the thoracic and lumbar spinal cord of the adult rat. Exp Neurol. 1999; 156(1): 191-204. PMid:10192790
53. Carelli S, Giallongo T, Gerace C, et al. Neural Stem Cell Transplantation in Experimental Contusive Model of Spinal Cord Injury. J Vis Exp. 2014. Available:
54. Knerlich-Lukoschus F, Krossa S, Krause J, et al. Impact of chemokines on the properties of spinal cord-derived neural progenitor cells in a rat spinal cord lesion model. J Neurosci Res. 2015; 93(4): 562-71. PMid:25491360
55. Knerlich-Lukoschus F, Juraschek M, Blömer U, et al. Force-dependent development of neuropathic central pain and time-related CCL2/CCR2 expression after graded spinal cord contusion injuries of the rat. J Neurotrauma. 2008; 25(5): 427-48. PMid:18338959
56. Murakami T, Kanchiku T, Suzuki H, et al. Anti-interleukin-6 receptor antibody reduces neuropathic pain following spinal cord injury in mice. Exp Ther Med. 2013; 6(5): 1194-198.
57. Ohri SS, Maddie MA, Zhang Y, et al. Deletion of the pro-apoptotic endoplasmic reticulum stress response effector CHOP does not result in improved locomotor function after severe contusive spinal cord injury. J Neurotrauma. 2012; 29(3): 579-88. PMid:21933012 PMCid:PMC3282015
58. Zhang YP, Burke DA, Shields LB, et al. Spinal Cord Contusion Based on Precise Vertebral Stabilization and Tissue Displacement Measured by Combined Assessment to Discriminate Small Functional Differences. J Neurotrauma. 2008; 25(10): 1227-240. PMid:18986224 PMCid:PMC2756607
59. McEwen ML, Springer JE. Quantification of locomotor recovery following spinal cord contusion in adult rats. J Neurotrauma. 2006; 23(11): 1632-653. PMid:17115910
60. Brambilla R, Bracchi-Ricard V, Hu W., et al. Inhibition of astroglial nuclear factor kappaB reduces inflammation and improves functional recovery after spinal cord injury. J Exp Med. 2005; 202(1): 145-56. PMid:15998793 PMCid:PMC2212896
61. Chen J, Xu XM, Xu Z, et al. Animal models of acute neurological injuries. Humana Press, 2009: 425-439.
62. Sroga JM, Jones TB, Kigerl KA, et al. Rats and mice exhibit distinct inflammatory reactions after spinal cord injury. J Comp Neurol. 2003; 462(2): 223-40. PMid:12794745
63. Norenberg MD, Smith J, Marcillo A. The pathology of human spinal cord injury: defining the problems. J Neurotrauma. 2004; 21(4): 429-40. PMid:15115592
64. Stoppini L, Buchs PA, Muller D. A simple method for organotypic cultures of nervous tissue. Jornal of Neuroscience Methods. 1991; 37(2): 173-82.
65. Abu-Rub M, McMahon S, Zeugolis D, et al. Spinal cord injury in vitro: Modelling axon growth inhibition. Drug Discov Today. 2010; 15(11-12): 436-443. PMid:20346411
66. Lee M, Lee ES, Kim YS, et al. Ischemic Injury-Specific Gene Expression in the Rat Spinal Cord Injury Model Using Hypoxia-Inducible System. Spine. 2005; 30(24): 2729-734. PMid:16371895
67. Shi R, Whitebone J. Conduction Deficits and Membrane Disruption of Spinal Cord Axons as a Function of Magnitude and Rate of Strain. J Neurophysiol. 2006; 95(6): 3384-390. PMid:16510778
68. Shearer MC, Niclou SP, Brown D, et al. The astrocyte/meningeal cell interface is a barrier to neurite outgrowth which can be overcome by manipulation of inhibitory molecules or axonal signaling pathways. Mol Cell Neurosci. 2003; 24(4): 913-25. PMid:14697658
69. Bregman BS, Mcatee M, Dai HN, et al. Neurotrophic Factors Increase Axonal Growth after Spinal Cord Injury and Transplantation in the Adult Rat. Experimental Neurology. 1997; 148(2): 475-94. PMid:9417827
70. Taccola G, Mladinic M, Nistri A. Dynamics of early locomotor network dysfunction following a focal lesion in an in vitro model of spinal injury Eur J Neurosci. 2010; 31(1): 60-78. PMid:20092556
71. Mandadi S, Nakanishi S, Takashima Y, et al. Locomotor Networks are Targets of Modulation by Sensory Transient Receptor Potential Vanilloid 1 and Transient Receptor Potential Melastatin 8 Channels. Neuroscience. 2009; 162(4): 1377-397. PMid:19482068 PMCid:PMC2880570
72. Wanner IB, Deik A, Torres M, et al. A new in vitro model of the glial scar inhibits axon growth. Glia. 2008; 56(15): 1691-709. PMid:18618667 PMCid:PMC3161731
73. Yoo JY, Hwang C, Hong HN. A Model of Glial Scarring Analogous to the Environment of a Traumatically Injured Spinal Cord Using Kainate. Department of Rehabilitation Medicine. 2016; 40(5): 757-68. PMid:27847705 PMCid:PMC5108702
74. East E, Golding J, Phillips J. A versatile 3D culture model facilitates monitoring of astrocytes undergoing reactive gliosis. J Tissue Eng Regen Med. 2009; 3(8): 634-46. PMid:19813215 PMCid:PMC2842570
75. Vyas A, Li Z, Aspalter M, et al. An in vitro model of adult mammalian nerve repair. Exp Neurol. 2010; 223(1): 112-18. PMid:19464291 PMCid:PMC2849894
76. Buss A, Pech K, Kakulas BA, et al. TGF-β1 and TGF-β2 expression after traumatic human spinal cord injury. J Spinal Cord. 2007; 46(5): 364-71. PMid:18040277

Rybachuk OA, Arkhypchuk IV, Lazarenko YuA. In vivo and in vitro models of traumatic injuries of the spinal cord. Cell and Organ Transplantology. 2017; 5(1):87-93. doi:10.22494/cot.v5i1.71

Creative Commons License Is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.