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Chapter 20 - Acute Spinal Cord Injury and Spinal Trauma

from Section 2 - Clinical Neurosurgical Diseases

Published online by Cambridge University Press:  04 January 2024

By
Dominique M. O. Higgins ,
Pavan S. Upadhyayula ,
Michael Argenziano  and
Paul McCormick
Edited by
Farhana Akter ,
Nigel Emptage ,
Florian Engert  and
Mitchel S. Berger
Farhana Akter
Affiliation:
Harvard University, Massachusetts
Nigel Emptage
Affiliation:
University of Oxford
Florian Engert
Affiliation:
Harvard University, Massachusetts
Mitchel S. Berger
Affiliation:
University of California, San Francisco
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Summary

Spinal cord injury(SCI) is a debilitating problem with a global incidence of 8–246 cases per million and an associated significant increase in healthcare cost. Research generally focuses on two broad categories: minimizing initial insult via modulation of primary and secondary injury cascades, or on novel therapeutic strategies aimed at recovering function. To this end, numerous SCI preclinical models have been developed, and promising clinical trials have arisen as a result, highlighting the importance of choosing the optimal model in relation to one’s scientific question. We highlight relevant spinal cord anatomy, embryology, and the pathophysiology of SCI with a focus on how these factors relate to preclinical models of SCI and spinal cord trauma, and hope to highlight important factors necessary for future research.

Type
Chapter
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Neuroscience for Neurosurgeons , pp. 278 - 290
Publisher: Cambridge University Press
Print publication year: 2024

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References

Abdullahi, D, Annuar, AA, Mohamad, M, Aziz, I, Sanusi, J. Experimental spinal cord trauma: a review of mechanically induced spinal cord injury in rat models. Rev Neurosci 2017:28:15–20. https://doi.org/10.1515/revneuro-2016-0050.Google Scholar
Ahuja, CS, Wilson, JR, Novi, S, et al. Traumatic spinal cord injury. Nat Rev Dis Primers (2017;3:17018. https://doi.org/10.1038/nrdp.2017.18.Google Scholar
Ajiboye, AB, Willett, FR, Young, DR, et al. Restoration of reaching and grasping movements through brain-controlled muscle stimulation in a person with tetraplegia: a proof-of-concept demonstration. Lancet 2017;389:1821–30. https://doi.org/10.1016/S0140-6736(17)30601-3.Google Scholar
Alizadeh, A, Dyck, SM, Karimi-Abdolrezaee, S. Myelin damage and repair in pathologic CNS: challenges and prospects. Front Mol Neurosci 2015;8:35. https://doi.org/10.3389/fnmol.2015.00035.Google Scholar
Alizadeh, A, Dyck, SM, Karimi-Abdolrezaee, S. Traumatic spinal cord injury: an overview of pathophysiology, models and acute injury mechanisms. Front Neurol 2019:10:282. https://doi.org/10.3389/fneur.2019.00282Google Scholar
Amit, I, Garber, M, Chevrier, N, et al. Unbiased reconstruction of a mammalian transcriptional network mediating pathogen responses. Science 2009;326:257–63. https://doi.org/10.1126/science.1179050.Google Scholar
Anderson, DK, Means, ED. Iron-induced lipid peroxidation in spinal cord: protection with mannitol and methylprednisolone. J Free Radic Biol Med 1985;1:59–64. https://doi.org/10.1016/0748-5514(85)90030-3.CrossRefGoogle ScholarPubMed
Anderson, DK, Saunders, RD, Demediuk, P, et al. Lipid hydrolysis and peroxidation in injured spinal cord: partial protection with methylprednisolone or vitamin E and selenium. Cent Nerv Syst Trauma 1985;2:257–67. https://doi.org/10.1089/cns.1985.2.257.Google Scholar
Aslan, A, Cemek, M, Eser, O, et al. Does dexmedetomidine reduce secondary damage after spinal cord injury? An experimental study. Eur Spine J 2009;18:336–44. https://doi.org/10.1007/s00586-008-0872-x.Google ScholarPubMed
Badimon, A, Strasburger, HJ, Ayata, P, et al. Negative feedback control of neuronal activity by microglia. Nature 2020;586:417–23. https://doi.org/10.1038/s41586-020-2777-8.Google Scholar
Baker, SN, Perez, MA. Reticulospinal contributions to gross hand function after human spinal cord injury. J Neurosci 2017;37:9778–84. https://doi.org/10.1523/JNEUROSCI.3368-16.2017.CrossRefGoogle ScholarPubMed
Ballermann, M, Fouad, K. Spontaneous locomotor recovery in spinal cord injured rats is accompanied by anatomical plasticity of reticulospinal fibers. Eur J Neurosci 2006;23:1988–96. https://doi.org/10.1111/j.1460-9568.2006.04726.x.Google Scholar
Barrière, G, Leblond, H, Provencher, J, Rossignol, S. Prominent role of the spinal central pattern generator in the recovery of locomotion after partial spinal cord injuries. J Neurosci 2008;28:3976–87. https://doi.org/10.1523/JNEUROSCI.5692-07.2008.Google Scholar
Barut, S, Canbolat, A, Bilge, T, Aydin, Y, Cokneşeli, B, Kaya, U. Lipid peroxidation in experimental spinal cord injury: time-level relationship. Neurosurg Rev 1993;16:53–9. https://doi.org/10.1007/BF00308614.Google Scholar
Basso, DM, Beattie, MS, Bresnahan, JC, et al. MASCIS evaluation of open field locomotor scores: effects of experience and teamwork on reliability. Multicenter animal spinal cord injury study. J Neurotrauma 1996;13:343–59. https://doi.org/10.1089/neu.1996.13.343.CrossRefGoogle ScholarPubMed
Basso, DM, Fisher, LC, Anderson, AJ, Jakeman, LB, McTigue, DM, Popovich, PG. Basso Mouse Scale for locomotion detects differences in recovery after spinal cord injury in five common mouse strains. J. Neurotrauma 2006;23:635–59. https://doi.org/10.1089/neu.2006.23.635.Google Scholar
Beattie, MS, Farooqui, AA, Bresnahan, JC. Review of current evidence for apoptosis after spinal cord injury. J Neurotrauma 2000;17:915–25. https://doi.org/10.1089/neu.2000.17.915.CrossRefGoogle ScholarPubMed
Bennett, GJ, Abdelmoumene, M, Hayashi, H, Dubner, R. Physiology and morphology of substantia gelatinosa neurons intracellularly stained with horseradish peroxidase. J Comp Neurol 1980;194:809–27. https://doi.org/10.1002/cne.901940407.Google Scholar
Bennett, GJ, Abdelmoumene, M, Hayashi, H, Hoffert, MJ, Dubner, R. Spinal cord layer I neurons with axon collaterals that generate local arbors. Brain Res 1981;209:421–6. https://doi.org/10.1016/0006-8993(81)90164-5.CrossRefGoogle ScholarPubMed
Bracken, MB, Holford, TR. Neurological and functional status 1 year after acute spinal cord injury: estimates of functional recovery in National Acute Spinal Cord Injury Study II from results modeled in National Acute Spinal Cord Injury Study III. J Neurosurg 2002;96:259–66. https://doi.org/10.3171/spi.2002.96.3.0259.Google ScholarPubMed
Bracken, MB, Shepard, MJ, Holford, TR, et al. Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury. Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. National Acute Spinal Cord Injury Study. JAMA 1997;277:1597–604.Google Scholar
Breazile, JE, Kitchell, RL. A study of fiber systems within the spinal cord of the domestic pig that subserve pain. J Comp Neurol 1968;133:373–82. https://doi.org/10.1002/cne.901330307.Google Scholar
Bunge, RP, Puckett, WR, Becerra, JL, Marcillo, A, Quencer, RM. 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 1993;59:75–89.Google ScholarPubMed
Carrico, KM, Vaishnav, R, Hall, ED. Temporal and spatial dynamics of peroxynitrite-induced oxidative damage after spinal cord contusion injury. J Neurotrauma 2009;26:1369–78. https://doi.org/10.1089/neu.2008-0870.CrossRefGoogle ScholarPubMed
Casha, S, Yu, WR, Fehlings, MG. Oligodendroglial apoptosis occurs along degenerating axons and is associated with FAS and p75 expression following spinal cord injury in the rat. Neuroscience 2001;103:203–18. https://doi.org/10.1016/s0306-4522(00)00538-8.CrossRefGoogle ScholarPubMed
Casha, S, Yu, WR, Fehlings, MG. FAS deficiency reduces apoptosis, spares axons and improves function after spinal cord injury. Exp Neurol 2005;196:390–400. https://doi.org/10.1016/j.expneurol.2005.08.020.CrossRefGoogle ScholarPubMed
Chaudhary, U, Birbaumer, N, Ramos-Murguialday, A. Brain–computer interfaces for communication and rehabilitation. Nat Rev Neurol 2016;12:513–25. https://doi.org/10.1038/nrneurol.2016.113.Google Scholar
Cheriyan, T, Ryan, DJ, Weinreb, JH, et al. Spinal cord injury models: a review. Spinal Cord 2014;52:588–95. https://doi.org/10.1038/sc.2014.91.Google Scholar
Choo, AM, Liu, J, Dvorak, M, Tetzlaff, W, Oxland, TR. Secondary pathology following contusion, dislocation, and distraction spinal cord injuries. Exp Neurol 2008;212: 490–506. https://doi.org/10.1016/j.expneurol.2008.04.038.Google Scholar
Choo, AM-T, Liu, J, Liu, Z, Dvorak, M, Tetzlaff, W, Oxland, TR. Modeling spinal cord contusion, dislocation, and distraction: characterization of vertebral clamps, injury severities, and node of Ranvier deformations. J Neurosci Methods 2009;181:6–17. https://doi.org/10.1016/j.jneumeth.2009.04.007.Google Scholar
Courtine, G, Song, B, Hoy, RR, et al. Recovery of supraspinal control of stepping via indirect propriospinal relay connections after spinal cord injury. Nat Med 2008;14:69–74. https://doi.org/10.1038/nm1682.Google Scholar
Curtis, E, Martin, JR, Gabel, B, et al. A first-in-human, Phase I study of neural stem cell transplantation for chronic spinal cord injury. Cell Stem Cell 2018;22:941–50. https://doi.org/10.1016/j.stem.2018.05.014.Google Scholar
Dabney, KW, Ehrenshteyn, M, Agresta, CA, et al. A model of experimental spinal cord trauma based on computer-controlled intervertebral distraction: characterization of graded injury. Spine 2004;29:2357–64. https://doi.org/10.1097/01.brs.0000143108.65385.74.Google Scholar
Demopoulos, HB, Flamm, ES, Seligman, ML, Pietronigro, DD, Tomasula, J, DeCrescito, V. Further studies on free-radical pathology in the major central nervous system disorders: effect of very high doses of methylprednisolone on the functional outcome, morphology, and chemistry of experimental spinal cord impact injury. Can J Physiol Pharmacol 1982;60:1415–24. https://doi.org/10.1139/y82-210.Google Scholar
Domínguez-Rodríguez, LE, Stecina, K, García-Ramírez, DL, et al. Candidate interneurons mediating the resetting of the locomotor rhythm by extensor group I afferents in the cat. Neuroscience 2020;450:96–112. https://doi.org/10.1016/j.neuroscience.2020.09.017.Google Scholar
Eccles, JC, Eccles, RM, Lundberg, A. The convergence of monosynaptic excitatory afferents on to many different species of alpha motoneurones. J Physiol 1957;137:22–50. https://doi.org/10.1113/jphysiol.1957.sp005794.Google Scholar
Ferretti, P, Mackay, M, Walder, S. The developing human spinal cord contains distinct populations of neural precursors. Neurodegener Dis 2006;3:38–44. https://doi.org/10.1159/000092091.CrossRefGoogle ScholarPubMed
Filli, L, Engmann, AK, Zörner, B, et al. Bridging the gap: a reticulo-propriospinal detour bypassing an incomplete spinal cord injury. J Neurosci 2014;34:13399–410. https://doi.org/10.1523/JNEUROSCI.0701-14.2014.Google Scholar
Fougerousse, F, Bullen, P, Herasse, M, et al. Human–mouse differences in the embryonic expression patterns of developmental control genes and disease genes. Hum Mol Genet 2000;9:165–73. https://doi.org/10.1093/hmg/9.2.165.Google Scholar
Frigon, A. The cat model of spinal cord injury. In Aldskogius, H. (Ed.), Animal Models of Spinal Cord Repair. Humana Press, 2013; 159–83.Google Scholar
Fukuda, S, Nakamura, T, Kishigami, Y, et al. New canine spinal cord injury model free from laminectomy. Brain Res Brain Res Protoc 2005;14:171–80. https://doi.org/10.1016/j.brainresprot.2005.01.001.Google Scholar
Furlan, JC, Sakakibara, BM, Miller, WC, Krassioukov, AV. Global incidence and prevalence of traumatic spinal cord injury. Can J Neurol Sci 2013;40:456–64. https://doi.org/10.1017/s0317167100014530.CrossRefGoogle ScholarPubMed
Gerasimenko, YP, Avelev, VD, Nikitin, OA, Lavrov, IA. Initiation of locomotor activity in spinal cats by epidural stimulation of the spinal cord. Neurosci Behav Physiol 2003;33:247–54. https://doi.org/10.1023/a:1022199214515.CrossRefGoogle ScholarPubMed
Ghosh, A, Fleiss, F, Sydekum, E, et al. Rewiring of hindlimb corticospinal neurons after spinal cord injury. Nat Neurosci 2010;13:97–104. https://doi.org/10.1038/nn.2448.Google Scholar
Göritz, C, Dias, DO, Tomilin, N, Barbacid, M, Shupliakov, O, Frisén, J. A pericyte origin of spinal cord scar tissue. Science 2011; 333:238–42 https://doi.org/10.1126/science.1203165.CrossRefGoogle ScholarPubMed
Grillner, S, Zangger, P. On the central generation of locomotion in the low spinal cat. Exp Brain Res 1979;34:241–61. https://doi.org/10.1007/BF00235671.Google Scholar
Guger, C, Edlinger, G, Harkam, W, Niedermayer, I, Pfurtscheller, G. How many people are able to operate an EEG-based brain-computer interface (BCI)? IEEE Trans Neural Syst Rehabil Eng 2003;11:145–7. https://doi.org/10.1109/TNSRE.2003.814481.Google Scholar
Hackett, AR, Lee, D-H, Dawood, A, et al. STAT3 and SOCS3 regulate NG2 cell proliferation and differentiation after contusive spinal cord injury. Neurobiol Dis 2016;89:10–22. https://doi.org/10.1016/j.nbd.2016.01.017Google Scholar
Hall, ED, Braughler, JM. Effects of intravenous methylprednisolone on spinal cord lipid peroxidation and Na+ + K+)-ATPase activity. Dose–response analysis during 1st hour after contusion injury in the cat. J Neurosurg 1982;57:247–53. https://doi.org/10.3171/jns.1982.57.2.0247.Google Scholar
Hall, ED, Wolf, DL. A pharmacological analysis of the pathophysiological mechanisms of posttraumatic spinal cord ischemia. J Neurosurg 1986;64:951–61. https://doi.org/10.3171/jns.1986.64.6.0951.CrossRefGoogle ScholarPubMed
Hall, ED, Yonkers, PA, Andrus, PK, Cox, JW, Anderson, DK. Biochemistry and pharmacology of lipid antioxidants in acute brain and spinal cord injury. J Neurotrauma 1992;9(Suppl 2):S425–42.Google Scholar
Hawryluk, G, Whetstone, W, Saigal, R, et al. Mean arterial blood pressure correlates with neurological recovery after human spinal cord injury: analysis of high frequency physiologic data. J Neurotrauma 2015;32:1958–67. https://doi.org/10.1089/neu.2014.3778.CrossRefGoogle ScholarPubMed
Heller, RA, Seelig, J, Bock, T, et al. Relation of selenium status to neuro-regeneration after traumatic spinal cord injury. J Trace Elem Med Biol 2019;51:141–9. https://doi.org/10.1016/j.jtemb.2018.10.006.Google Scholar
Honda, CN, Lee, CL. Immunohistochemistry of synaptic input and functional characterizations of neurons near the spinal central canal. Brain Res 1985;343:120–8. https://doi.org/10.1016/0006-8993(85)91165-5.CrossRefGoogle ScholarPubMed
Hu, R., Zhou, J, Luo, C, et al. Glial scar and neuroregeneration: histological, functional, and magnetic resonance imaging analysis in chronic spinal cord injury. J Neurosurg Spine 2010;13:169–80. https://doi.org/10.3171/2010.3.SPINE09190.Google Scholar
Inman, DM, Steward, O. Ascending sensory, but not other long-tract axons, regenerate into the connective tissue matrix that forms at the site of a spinal cord injury in mice. J Comp Neurol 2003;462:431–49. https://doi.org/10.1002/cne.10768.CrossRefGoogle Scholar
Jankowska, E, Maxwell, DJ, Bannatyne, BA. On coupling and decoupling of spinal interneuronal networks. Arch Ital Biol 2007;145:235–50.Google Scholar
Jeffery, ND, Hamilton, L, Granger, N. Designing clinical trials in canine spinal cord injury as a model to translate successful laboratory interventions into clinical practice. Vet Rec 2011;168:102–07. https://doi.org/10.1136/vr.d475.Google Scholar
Jeffery, ND, Smith, PM, Lakatos, A, Ibanez, C, Ito, D, Franklin, RJM. Clinical canine spinal cord injury provides an opportunity to examine the issues in translating laboratory techniques into practical therapy. Spinal Cord 2006;44:584–93. https://doi.org/10.1038/sj.sc.3101912.Google Scholar
Jones, CF, Lee, JHT, Kwon, BK, Cripton, PA. Development of a large-animal model to measure dynamic cerebrospinal fluid pressure during spinal cord injury: laboratory investigation. J Neurosurg Spine 2012;16:624–35. https://doi.org/10.3171/2012.3.SPINE11970.Google Scholar
Jordan, LM, Liu, J, Hedlund, PB, Akay, T, Pearson, KG. Descending command systems for the initiation of locomotion in mammals. Brain Res Rev 2008;57:183–91. https://doi.org/10.1016/j.brainresrev.2007.07.019.Google Scholar
Josephson, A, Greitz, D, Klason, T, Olson, L, Spenger, C. A spinal thecal sac constriction model supports the theory that induced pressure gradients in the cord cause edema and cyst formation. Neurosurgery 2001;48:636–45; discussion 645–6. https://doi.org/10.1097/00006123-200103000-00039.Google Scholar
Kakulas, BA. Neuropathology: the foundation for new treatments in spinal cord injury. Spinal Cord 2004;42:549–63. https://doi.org/10.1038/sj.sc.3101670.Google Scholar
Kamencic, H, Griebel, RW, Lyon, AW, Paterson, PG, Juurlink, BH. Promoting glutathione synthesis after spinal cord trauma decreases secondary damage and promotes retention of function. FASEB J 2001;15:243–50. https://doi.org/10.1096/fj.00-0228com.Google Scholar
Kawase, T, Sakurada, T, Koike, Y, Kansaku, K. A hybrid BMI-based exoskeleton for paresis: EMG control for assisting arm movements. J Neural Eng 2017;14:016015. https://doi.org/10.1088/1741-2552/aa525f.Google Scholar
Kennedy, PR. Corticospinal, rubrospinal and rubro-olivary projections: a unifying hypothesis. Trends Neurosci 1990;13:474–9. https://doi.org/10.1016/0166-2236(90)90079-p.Google Scholar
Kubota, K, Saiwai, H, Kumamaru, H, et al. Myeloperoxidase exacerbates secondary injury by generating highly reactive oxygen species and mediating neutrophil recruitment in experimental spinal cord injury. Spine 2012;37:1363–9. https://doi.org/10.1097/BRS.0b013e31824b9e77.Google Scholar
Kucher, K, Johns, D, Maier, D, et al. First-in-man intrathecal application of neurite growth-promoting anti-Nogo-A antibodies in acute spinal cord injury. Neurorehabil Neural Repair 2018;32:578–89. https://doi.org/10.1177/1545968318776371.Google Scholar
Kumar, H, Choi, H, Jo, M-J, et al. Neutrophil elastase inhibition effectively rescued angiopoietin-1 decrease and inhibits glial scar after spinal cord injury. Acta Neuropathol Commun 2018;6:73. https://doi.org/10.1186/s40478-018-0576-3.Google Scholar
Lemke, M, Frei, B, Ames, BN, Faden, AI. Decreases in tissue levels of ubiquinol-9 and -10, ascorbate and alpha-tocopherol following spinal cord impact trauma in rats. Neurosci Lett 1990;108:201–06. https://doi.org/10.1016/0304-3940(90)90731-n.Google Scholar
Lemon, RN. Descending pathways in motor control. Annu Rev Neurosci 2008;31:195–218. https://doi.org/10.1146/annurev.neuro.31.060407.125547.Google Scholar
Levi, AD, Anderson, KD, Okonkwo, DO, et al. Clinical outcomes from a multi-center study of human neural stem cell transplantation in chronic cervical spinal cord injury. J Neurot-rauma 2019;36:891–902. https://doi.org/10.1089/neu.2018.5843.Google Scholar
Levi, L, Wolf, A, Belzberg, H. Hemodynamic parameters in patients with acute cervical cord trauma: description, intervention, and prediction of outcome. Neurosurgery 1993;33:1007–16; discussion 1016–7.Google Scholar
Levine, JM, Levine, GJ, Porter, BF, Topp, K, Noble-Haeusslein, LJ. Naturally occurring disk herniation in dogs: an opportunity for pre-clinical spinal cord injury research. J Neurotrauma 2011;28:675–88. https://doi.org/10.1089/neu.2010.1645.Google Scholar
Liu, D, Liu, J, Sun, D, Wen, J. The time course of hydroxyl radical formation following spinal cord injury: the possible role of the iron-catalyzed Haber–Weiss reaction. J Neurotrauma 2004;21:805–16. https://doi.org/10.1089/0897715041269650.Google Scholar
Liu, D, Sybert, TE, Qian, H, Liu, J. Superoxide production after spinal injury detected by microperfusion of cytochrome c. Free Radic Biol Med 1998;25:298–304. https://doi.org/10.1016/s0891-5849(98)00055-0.Google Scholar
Liu, J-B, Tang, T-S, Xiao, D-S. Changes of free iron contents and its correlation with lipid peroxidation after experimental spinal cord injury. Chin J Traumatol 2004:7:229–32.Google Scholar
Lucas, JH, Wheeler, DG, Guan, Z, Suntres, Z, Stokes, BT. Effect of glutathione augmentation on lipid peroxidation after spinal cord injury. J Neurotrauma 2002;19:763–75. https://doi.org/10.1089/08977150260139138.Google Scholar
Ma, M, Basso, DM, Walters, P, Stokes, BT, Jakeman, LB. Behavioral and histological outcomes following graded spinal cord contusion injury in the C57Bl/6 mouse. Exp Neurol 2001;169:239–54. https://doi.org/10.1006/exnr.2001.7679.Google Scholar
Mannen, H, Sugiura, Y. Reconstruction of neurons of dorsal horn proper using Golgi-stained serial sections. J Comp Neurol 1976;168:303–12. https://doi.org/10.1002/cne.901680205.Google Scholar
Martinez, M, Delivet-Mongrain, H, Leblond, H, Rossignol, S. Recovery of hindlimb locomotion after incomplete spinal cord injury in the cat involves spontaneous compensatory changes within the spinal locomotor circuitry. J Neurophysiol 2011;106:1969–84. https://doi.org/10.1152/jn.00368.2011.Google Scholar
Martirosyan, N L, Kalani, MYS, Bichard, WD, et al. Cerebrospinal fluid drainage and induced hypertension improve spinal cord perfusion after acute spinal cord injury in pigs. Neurosurgery 2015;76:461–8; discussion 468–9. https://doi.org/10.1227/NEU.0000000000000638.Google Scholar
Mazensky, D, Flesarova, S, Sulla, I. Arterial blood supply to the spinal cord in animal models of spinal cord injury. A review. Anat Rec 2017;300:2091–106. https://doi.org/10.1002/ar.23694.Google Scholar
Metz, GA, Curt, A, van de Meent, H, Klusman, I, Schwab, ME, Dietz, V. Validation of the weight-drop contusion model in rats: a comparative study of human spinal cord injury. J Neurotrauma 2000;17:1–17. https://doi.org/10.1089/neu.2000.17.1.Google Scholar
Monyer, H, Hartley, DM, Choi, D W. 21-Aminosteroids attenuate excitotoxic neuronal injury in cortical cell cultures. Neuron 1990;5:121–6. https://doi.org/10.1016/0896-6273(90)90302-v.Google Scholar
Moore, SA, Granger, N, Olby, NJ, et al. Targeting translational successes through CANSORT-SCI: using pet dogs to identify effective treatments for spinal cord injury. J Neurotrauma 2017;34:2007–18. https://doi.org/10.1089/neu.2016.4745.Google Scholar
Moore, SA, Zidan, N, Spitzbarth, I, et al. Development of an International Canine Spinal Cord Injury observational registry: a collaborative data-sharing network to optimize translational studies of SCI. Spinal Cord 2018;56:656–65. https://doi.org/10.1038/s41393-018-0145-4.Google Scholar
Müller, K, Gürster, D. Hydroxyl radical damage to DNA sugar and model membranes induced by anthralin (dithranol). Biochem Pharmacol 1993;46:1695–704. https://doi.org/10.1016/0006-2952(93)90573-f.Google Scholar
Nashmi, R, Fehlings, MG. Changes in axonal physiology and morphology after chronic compressive injury of the rat thoracic spinal cord. Neuroscience 2001;104:235–51. https://doi.org/10.1016/s0306-4522(01)00009-4.Google Scholar
Nathan, PW. Effects on movement of surgical incisions into the human spinal cord. Brain 1994;117(Pt 2):337–46. https://doi.org/10.1093/brain/117.2.337.Google Scholar
Navarro, R, Juhas, S, Keshavarzi, S, et al. Chronic spinal compression model in minipigs: a systematic behavioral, qualitative, and quantitative neuropathological study. J Neurotrauma 2012;29:499–513. https://doi.org/10.1089/neu.2011.2076.Google Scholar
Neirinckx, V, Coste, C, Franzen, F, Gothot, A, Rogister, B, Wislet, S. Neutrophil contribution to spinal cord injury and repair. J Neuroinflammation 2014;11:150. https://doi.org/10.1186/s12974-014-0150-2.Google Scholar
Nesathurai, S, Graham, WA, Mansfield, K, et al. Model of traumatic spinal cord injury in Macaca fascicularis: similarity of experimental lesions created by epidural catheter to human spinal cord injury. J Med Primatol 2006;35:401–04. https://doi.org/10.1111/j.1600-0684.2006.00162.x.Google Scholar
Nguyen, HX, O’Barr, TJ, Anderson, AJ. Polymorphonuclear leukocytes promote neurotoxicity through release of matrix metalloproteinases, reactive oxygen species, and TNF-alpha. J Neurochem 2007;102:900–12. https://doi.org/10.1111/j.1471-4159.2007.04643.x.CrossRefGoogle ScholarPubMed
Nielsen, JB. How we walk: central control of muscle activity during human walking. Neuroscientist 2003;9:195–204. https://doi.org/10.1177/1073858403009003012.CrossRefGoogle ScholarPubMed
Noble, LJ, Wrathall, JR. Spinal cord contusion in the rat: morphometric analyses of alterations in the spinal cord. Exp Neurol 1985;88:135–49. https://doi.org/10.1016/0014-4886(85)90119-0.Google Scholar
Norenberg, MD, Smith, J, Marcillo, A. The pathology of human spinal cord injury: defining the problems. J Neurotrauma 2004;21:429–40. https://doi.org/10.1089/089771504323004575.Google Scholar
O’Rahilly, RR, Müller, F. The Embryonic Human Brain: An Atlas Of Developmental Stages. John Wiley & Sons, 2006.Google Scholar
O’Shea, TM, Burda, JE, Sofroniew, MV. Cell biology of spinal cord injury and repair. J Clin Invest 2017;127:3259–70. https://doi.org/10.1172/JCI90608.Google Scholar
Ohtani, K, Abe, H, Kadoya, S. Beneficial effects of methylprednisolone sodium succinate in the treatment of acute spinal cord injury. Sekitsui Sekizui 1994;7:633–47.Google Scholar
Okon, EB, Streijger, F, Lee, JHT, Anderson, LM, Russell, AK, Kwon, BK. Intraparenchymal microdialysis after acute spinal cord injury reveals differential metabolic responses to contusive versus compressive mechanisms of injury. J Neurotrauma 2013;30:1564–76. https://doi.org/10.1089/neu.2013.2956.Google Scholar
Onifer, SM, Smith, GM, Fouad, K. Plasticity after spinal cord injury: relevance to recovery and approaches to facilitate it. Neurotherapeutics 2011;8:283–93. https://doi.org/10.1007/s13311-011-0034-4.Google Scholar
Orr, MB, Gensel, JC. Spinal cord injury scarring and inflammation: therapies targeting glial and inflammatory responses. Neurotherapeutics 2018;15:541–53. https://doi.org/10.1007/s13311-018-0631-6.CrossRefGoogle ScholarPubMed
Petersen, TH, Willerslev-Olsen, M, Conway, BA, Nielsen, JB. The motor cortex drives the muscles during walking in human subjects. J Physiol 2012;590:2443–52. https://doi.org/10.1113/jphysiol.2012.227397.Google Scholar
Pietronigro, DD, Hovsepian, M, Demopoulos, HB, Flamm, ES. Loss of ascorbic acid from injured feline spinal cord. J Neurochem 1983;41:1072–6. https://doi.org/10.1111/j.1471-4159.1983.tb09053.x.Google Scholar
Pointillart, V, Petitjean, ME, Wiart, L, et al. Pharmacological therapy of spinal cord injury during the acute phase. Spinal Cord 2000;38:71–6. https://doi.org/10.1038/sj.sc.3100962.Google Scholar
Ramesh, T, Nagula, SV, Tardieu, GG, et al. Update on the notochord including its embryology, molecular development, and pathology: a primer for the clinician. Cureus 2017;9:e1137. https://doi.org/10.7759/cureus.1137Google Scholar
Readdy, WJ, Dhall, SS. Vasopressor administration in spinal cord injury: should we apply a universal standard to all injury patterns? Neural Regeneration Res 2016);11:420–1. https://doi.org/10.4103/1673-5374.179051.Google Scholar
Rexed, B. The cytoarchitectonic organization of the spinal cord in the cat. J Comp Neurol 1952;96:414–95. https://doi.org/10.1002/cne.900960303.Google Scholar
Rexed, B. A cytoarchitectonic atlas of the spinal cord in the cat. J Comp Neurol 1954;100:297–379. https://doi.org/10.1002/cne.901000205.Google Scholar
Rohm, M, Schneider, M, Müller, C, et al. Hybrid brain–computer interfaces and hybrid neuroprostheses for restoration of upper limb functions in individuals with high-level spinal cord injury. Artif Intell Med 2013;59:133–42. https://doi.org/10.1016/j.artmed.2013.07.004.Google Scholar
Rossignol, S, Schwab, M, Schwartz, M, Fehlings, MG. Spinal cord injury: time to move? J Neurosci 2007;27:11782–92. https://doi.org/10.1523/JNEUROSCI.3444-07.2007.Google Scholar
Rothwell, J. Ascending and descending pathways of the spinal cord. In Rothwell, J (Ed.), Control of Human Voluntary Movement. Springer Netherlands, 1994; 217–51.Google Scholar
Rowland, JW, Hawryluk, GWJ, Kwon, B, Fehlings, MG. Current status of acute spinal cord injury pathophysiology and emerging therapies: promise on the horizon. Neurosurg. Focus 2008;25:E2. https://doi.org/10.3171/FOC.2008.25.11.E2.Google Scholar
Saiwai, H, Ohkawa, Y, Yamada, H, et al. The LTB4–BLT1 axis mediates neutrophil infiltration and secondary injury in experimental spinal cord injury. Am J Pathol 2010;176:2352–66. https://doi.org/10.2353/ajpath.2010.090839Google Scholar
Schoenen, J. Dendritic organization of the human spinal cord: the motoneurons. J Comp Neurol 1982a;211:226–47. https://doi.org/10.1002/cne.902110303.Google Scholar
Schoenen, J. The dendritic organization of the human spinal cord: the dorsal horn. Neuroscience 1982b;7:2057–87. https://doi.org/10.1016/0306-4522(82)90120-8.CrossRefGoogle ScholarPubMed
Schomberg, DT, Miranpuri, GS, Chopra, A, et al. Translational relevance of swine models of spinal cord injury. J Neurotrauma 2017;34:541–51. https://doi.org/10.1089/neu.2016.4567.Google Scholar
Schucht, P, Raineteau, O, Schwab, ME, Fouad, K. Anatomical correlates of locomotor recovery following dorsal and ventral lesions of the rat spinal cord. Exp Neurol 2002;176:143–53. https://doi.org/10.1006/exnr.2002.7909.Google Scholar
Semple, BD, Blomgren, K, Gimlin, K, Ferriero, DM, Noble-Haeusslein, LJ. Brain development in rodents and humans: Identifying benchmarks of maturation and vulnerability to injury across species. Prog Neurobiol 2013;106–107:1–16. https://doi.org/10.1016/j.pneurobio.2013.04.001.Google Scholar
Sharif-Alhoseini, M, Khormali, M, Rezaei, M, et al. Animal models of spinal cord injury: a systematic review. Spinal Cord 2017;55:714–21. https://doi.org/10.1038/sc.2016.187Google Scholar
Simon, F, Oberhuber, A. Ischemia and reperfusion injury of the spinal cord: experimental strategies to examine postischemic paraplegia. Neural Regeneration Res 2016;11:414–15. https://doi.org/10.4103/1673-5374.179050.Google Scholar
Stockwell, BR, Freidmann Angeli, JP, Bayir, H, et al. Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell 2017;171:273–85. https://doi.org/10.1016/j.cell.2017.09.021.Google Scholar
Strauch, JT, Lauten, A, Zhang, N, Wahlers, T, Griepp, RB. Anatomy of spinal cord blood supply in the pig. Ann Thorac Surg 2007);83:2130–4. https://doi.org/10.1016/j.athoracsur.2007.01.060.Google Scholar
Su, L-J, Zhang, J-H, Gomez, H, et al. Reactive oxygen species-induced lipid peroxidation in apoptosis, autophagy, and ferroptosis. Oxid Med Cell Longev 2019:2019:5080843. https://doi.org/10.1155/2019/5080843.Google Scholar
Tabakow, P, Jarmundowicz, W, Czapiga, B, et al. Transplantation of autologous olfactory ensheathing cells in complete human spinal cord injury. Cell Transplant 2013;22:1591–612. https://doi.org/10.3727/096368912X663532.Google Scholar
Tidoni, E, Gergondet, P, Fusco, G, Kheddar, A, Aglioti, SM. The role of audio-visual feedback in a thought-based control of a humanoid robot: a BCI study in healthy and spinal cord injured people. IEEE Trans Neural Syst Rehabil Eng 2017;25:772–81. https://doi.org/10.1109/TNSRE.2016.2597863.Google Scholar
Tohyama, T, Kinoshita, M, Kobayashi, K, et al. Contribution of propriospinal neurons to recovery of hand dexterity after corticospinal tract lesions in monkeys. Proc Natl Acad Sci U S A 2017;114:604–09. https://doi.org/10.1073/pnas.1610787114.Google Scholar
Totoiu, MO, Nistor, GI, Lane, TE, Keirstead, HS. Remyelination, axonal sparing, and locomotor recovery following transplantation of glial-committed progenitor cells into the MHV model of multiple sclerosis. Exp Neurol 2004;187:254–65. https://doi.org/10.1016/j.expneurol.2004.01.028.Google Scholar
Vale, FL, Burns, J, Jackson, AB, Hadley, MN. Combined medical and surgical treatment after acute spinal cord injury: results of a prospective pilot study to assess the merits of aggressive medical resuscitation and blood pressure management. J Neurosurg 1997;87:239–46. https://doi.org/10.3171/jns.1997.87.2.0239.Google Scholar
van der Scheer, JW, Martin Ginis, KA, Ditor, DS, et al. Effects of exercise on fitness and health of adults with spinal cord injury: a systematic review. Neurology 2017;89:736–45. https://doi.org/10.1212/WNL.0000000000004224.Google Scholar
Volpe, E, Sambucci, M, Battistini, L, Borsellino, G. Fas–Fas ligand: checkpoint of T cell functions in multiple sclerosis. Front Immunol 2016l7:382. https://doi.org/10.3389/fimmu.2016.00382.Google Scholar
Wang, X, Cao, K, Sun, X, et al. Macrophages in spinal cord injury: phenotypic and functional change from exposure to myelin debris. Glia 2015;63:635–51. https://doi.org/10.1002/glia.22774.Google Scholar
Werneburg, S, Feinberg, PA, Johnson, KM, Schafer, DP. A microglia–cytokine axis to modulate synaptic connectivity and function. Curr Opin Neurobiol 2017;47:138–45. https://doi.org/10.1016/j.conb.2017.10.002.Google Scholar
Whalen, MJ, Dalkara, T, You, Z, et al. Acute plasmalemma permeability and protracted clearance of injured cells after controlled cortical impact in mice. J Cereb Blood Flow Metab 2008;28:490–505. https://doi.org/10.1038/sj.jcbfm.9600544.Google Scholar
Whelan, PJ. Control of locomotion in the decerebrate cat. Prog Neurobiol 1996;49:481–515. https://doi.org/10.1016/0301-0082(96)00028-7.Google Scholar
Xiao, Z, Tang, F, Zhao, Y, et al. Significant improvement of acute complete spinal cord injury patients diagnosed by a combined criteria implanted with NeuroRegen scaffolds and mesenchymal stem cells. Cell Transplant 2018;27:907–15. https://doi.org/10.1177/0963689718766279.Google Scholar
Yune, TY, Lee, JY, Jiang, MH, Kim, DW, Choi, SY, Oh, TH. Systemic administration of PEP-1–SOD1 fusion protein improves functional recovery by inhibition of neuronal cell death after spinal cord injury. Free Radic Biol Med 2008;45:1190–200. https://doi.org/10.1016/j.freeradbiomed.2008.07.016.Google Scholar
Zakaryan, H, Cholakyans, V, Simonyan, L, et al. A study of lymphoid organs and serum proinflammatory cytokines in pigs infected with African swine fever virus genotype II. Arch Virol 2015;160:1407–14. https://doi.org/10.1007/s00705-015-2401-7.Google Scholar
Zhang, C, Chen, K, Han, X, et al. Diffusion tensor imaging in diagnosis of post-traumatic syringomyelia in spinal cord injury in rats. Med Sci Monit 2018;24:177–82. https://doi.org/10.12659/MSM.907955.Google Scholar
Zhang, N, Fang, M, Chen, H, Gou, F, Ding, M. Evaluation of spinal cord injury animal models. Neural Regeneration Res 2014;9:2008–12. https://doi.org/10.4103/1673-5374.143436.Google Scholar
Zivin, JA, DeGirolami, U. Spinal cord infarction: a highly reproducible stroke model. Stroke 1980;11:200–02. https://doi.org/10.1161/01.str.11.2.200.CrossRefGoogle ScholarPubMed
Zörner, B, Bachmann, LC, Filli, L, et al. Chasing central nervous system plasticity: the brainstem’s contribution to locomotor recovery in rats with spinal cord injury. Brain 2014;137:1716–32. https://doi.org/10.1093/brain/awu078.Google Scholar

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