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Spinal cord injury: overview of experimental approaches used to restore locomotor activity

  • Marc Fakhoury EMAIL logo
Published/Copyright: April 14, 2015
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Abstract

Spinal cord injury affects more than 2.5 million people worldwide and can lead to paraplegia and quadriplegia. Anatomical discontinuity in the spinal cord results in disruption of the impulse conduction that causes temporary or permanent changes in the cord’s normal functions. Although axonal regeneration is limited, damage to the spinal cord is often accompanied by spontaneous plasticity and axon regeneration that help improve sensory and motor skills. The recovery process depends mainly on synaptic plasticity in the preexisting circuits and on the formation of new pathways through collateral sprouting into neighboring denervated territories. However, spontaneous recovery after spinal cord injury can go on for several years, and the degree of recovery is very limited. Therefore, the development of new approaches that could accelerate the gain of motor function is of high priority to patients with damaged spinal cord. Although there are no fully restorative treatments for spinal injury, various rehabilitative approaches have been tested in animal models and have reached clinical trials. In this paper, a closer look will be given at the potential therapies that could facilitate axonal regeneration and improve locomotor recovery after injury to the spinal cord. This article highlights the application of several interventions including locomotor training, molecular and cellular treatments, and spinal cord stimulation in the field of rehabilitation research. Studies investigating therapeutic approaches in both animal models and individuals with injured spinal cords will be presented.


Corresponding author: Marc Fakhoury, Faculty of Medicine, Department of Neuroscience, University of Montreal, Montreal H3C 3J7, QC, Canada, Tel: +1 (514) 710-7060, e-mail:

Acknowledgment

The author is a recipient of an award from the Natural Sciences and Engineering Research Council of Canada.

Financial disclosure: The author declares no potential conflict of interest.

References

Alluin, O., Delivet-Mongrain, H., Gauthier, M.K., Fehlings, M.G., Rossignol, S., and Karimi-Abdolrezaee, S. (2014). Examination of the combined effects of chondroitinase ABC, growth factors and locomotor training following compressive spinal cord injury on neuroanatomical plasticity and kinematics. PLoS One 9, e111072.10.1371/journal.pone.0111072Search in Google Scholar PubMed PubMed Central

Anderson, K.D. (2004). Targeting recovery: priorities of the spinal cord-injured population. J. Neurotrauma 21, 1371–1383.10.1089/neu.2004.21.1371Search in Google Scholar PubMed

Antal, M. (1984). Termination areas of corticobulbar and corticospinal fibres in the rat. J. Hirnforsch. 25, 647–659.Search in Google Scholar

Anwer, S., Equebal, A., Palekar, T.J., Nezamuddin, M., Neyaz, O., and Alghadir, A. (2014). Effect of locomotor training on motor recovery and walking ability in patients with incomplete spinal cord injury: a case series. J. Phys. Ther. Sci. 26, 951–953.10.1589/jpts.26.951Search in Google Scholar PubMed PubMed Central

Bamford, J.A., Todd, K.G., and Mushahwar, V.K. (2010). The effects of intraspinal microstimulation on spinal cord tissue in the rat. Biomaterials 31, 5552–5563.10.1016/j.biomaterials.2010.03.051Search in Google Scholar PubMed PubMed Central

Barry, M.D., Bunday, K.L., Chen, R., and Perez, M.A. (2013). Selective effects of baclofen on use-dependent modulation of GABAB inhibition after tetraplegia. J. Neurosci. 33, 12898–12907.10.1523/JNEUROSCI.1552-13.2013Search in Google Scholar PubMed PubMed Central

Biran, R., Martin, D.C., and Tresco, P.A. (2005). Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays. Exp. Neurol. 195, 115–126.10.1016/j.expneurol.2005.04.020Search in Google Scholar PubMed

Bracken, M.B. (2001). Methylprednisolone and acute spinal cord injury: an update of the randomized evidence. Spine 26, S47–S54.10.1097/00007632-200112151-00010Search in Google Scholar PubMed

Bracken, M.B., Shepard, M.J., Hellenbrand, K.G., Collins, W.F., Leo, L.S., Freeman, D.F., Wagner, F.C., Flamm, E.S., Eisenberg, H.M., Goodman, J.H., et al. (1985). Methylprednisolone and neurological function 1 year after spinal cord injury. Results of the National Acute Spinal Cord Injury Study. J. Neurosurg. 63, 704–713.10.3171/jns.1985.63.5.0704Search in Google Scholar PubMed

Breslin, K. and Agrawal, D. (2012). The use of methylprednisolone in acute spinal cord injury: a review of the evidence, controversies, and recommendations. Pediatr. Emerg. Care 28, 1238–1245.10.1097/PEC.0b013e3182724434Search in Google Scholar PubMed

Brick, N. (2014). Locomotor training for walking after spinal cord injury. Orthop. Nurs. 33, 115–116.10.1097/NOR.0000000000000037Search in Google Scholar PubMed

Broderick, C.P., Radnitz, C.L., and Bauman, W.A. (1997). Diazepam usage in veterans with spinal cord injury. J. Spinal Cord Med. 20, 406–409.10.1080/10790268.1997.11719498Search in Google Scholar PubMed

Bruehlmeier, M., Dietz, V., Leenders, K.L., Roelcke, U., Missimer, J., and Curt, A. (1998). How does the human brain deal with a spinal cord injury? Eur. J. Neurosci. 10, 3918–3922.10.1046/j.1460-9568.1998.00454.xSearch in Google Scholar

Bunday, K.L., Tazoe, T., Rothwell, J.C., and Perez, M.A. (2014). Subcortical control of precision grip after human spinal cord injury. J. Neurosci. 34, 7341–7350.10.1523/JNEUROSCI.0390-14.2014Search in Google Scholar PubMed PubMed Central

Cardenas, D.D., Nieshoff, E.C., Suda, K., Goto, S., Sanin, L., Kaneko, T., Sporn, J., Parsons, B., Soulsby, M., Yang, R., et al. (2013). A randomized trial of pregabalin in patients with neuropathic pain due to spinal cord injury. Neurology 80, 533–539.10.1212/WNL.0b013e318281546bSearch in Google Scholar PubMed PubMed Central

Chen, G., Zhang, Z., Wang, S., and Lv, D. (2013). Combined treatment with FK506 and nerve growth factor for spinal cord injury in rats. Exp. Ther. Med. 6, 868–872.10.3892/etm.2013.1254Search in Google Scholar PubMed PubMed Central

Chiodo, A.E. and Saval, A. (2012). Intrathecal baclofen for the treatment of spinal myoclonus: a case series. J. Spinal Cord Med. 35, 64–67.10.1179/2045772311Y.0000000006Search in Google Scholar PubMed PubMed Central

Collinger, J.L., Foldes, S., Bruns, T.M., Wodlinger, B., Gaunt, R., and Weber, D.J. (2013). Neuroprosthetic technology for individuals with spinal cord injury. J. Spinal Cord Med. 36, 258–272.10.1179/2045772313Y.0000000128Search in Google Scholar PubMed PubMed Central

Crowe, M.J., Bresnahan, J.C., Shuman, S.L., Masters, J.N., Beattie, M.S. (1997). Apoptosis and delayed degeneration after spinal cord injury in rats and monkeys. Nat. Med. 3, 73–76.10.1038/nm0197-73Search in Google Scholar PubMed

Curtis, D.R., Gynther, B.D., Lacey, G., and Beattie, D.T. (1997). Baclofen: reduction of presynaptic calcium influx in the cat spinal cord in vivo. Exp. Brain Res. 113, 520–533.10.1007/PL00005604Search in Google Scholar PubMed

Dario, A. and Tomei, G. (2004). A benefit-risk assessment of baclofen in severe spinal spasticity. Drug Saf. 27, 799–818.10.2165/00002018-200427110-00004Search in Google Scholar PubMed

Edgerton, V.R. and Harkema, S. (2011). Epidural stimulation of the spinal cord in spinal cord injury: current status and future challenges. Exp. Rev. Neurother. 11, 1351–1353.10.1586/ern.11.129Search in Google Scholar PubMed PubMed Central

Engesser-Cesar, C., Anderson, A.J., Basso, D.M., Edgerton, V.R., and Cotman, C.W. (2005). Voluntary wheel running improves recovery from a moderate spinal cord injury. J. Neurotrauma 22, 157–171.10.1089/neu.2005.22.157Search in Google Scholar

Field-Fote, E.C., Lindley, S.D., and Sherman, A.L. (2005). Locomotor training approaches for individuals with spinal cord injury: a preliminary report of walking-related outcomes. J. Neurol. Phys. Ther. 29, 127–137.10.1097/01.NPT.0000282245.31158.09Search in Google Scholar

Gensert, J.M. and Goldman, J.E. (1997). Endogenous progenitors remyelinate demyelinated axons in the adult CNS. Neuron 19, 197–203.10.1016/S0896-6273(00)80359-1Search in Google Scholar

Goldshmit, Y., Lythgo, N., Galea, M.P., and Turnley, A.M. (2008). Treadmill training after spinal cord hemisection in mice promotes axonal sprouting and synapse formation and improves motor recovery. J. Neurotrauma 25, 449–465.10.1089/neu.2007.0392Search in Google Scholar

Guest, J.D., Hiester, E.D., and Bunge, R.P. (2005). Demyelination and Schwann cell responses adjacent to injury epicenter cavities following chronic human spinal cord injury. Exp. Neurol. 192, 384–393.10.1016/j.expneurol.2004.11.033Search in Google Scholar

Guggenmos, D.J., Azin, M., Barbay, S., Mahnken, J.D., Dunham, C., Mohseni, P., and Nudo, R.J. (2013). Restoration of function after brain damage using a neural prosthesis. Proc. Natl. Acad. Sci. USA 110, 21177–21182.10.1073/pnas.1316885110Search in Google Scholar

Hall, E.D. (2001). Pharmacological treatment of acute spinal cord injury: how do we build on past success? J. Spinal Cord Med. 24, 142–146.10.1080/10790268.2001.11753571Search in Google Scholar

Hamid, S. and Hayek, R. (2008). Role of electrical stimulation for rehabilitation and regeneration after spinal cord injury: an overview. Eur. Spine J. 17, 1256–1269.10.1007/s00586-008-0729-3Search in Google Scholar

Han, J.J., Massagli, T.L., and Jaffe, K.M. (2004). Fibrocartilaginous embolism – an uncommon cause of spinal cord infarction: a case report and review of the literature. Arch. Phys. Med. Rehabil. 85, 153–157.10.1016/S0003-9993(03)00289-2Search in Google Scholar

Harkema, S., Gerasimenko, Y., Hodes, J., Burdick, J., Angeli, C., Chen, Y., Ferreira, C., Willhite, A., Rejc, E., Grossman, R.G., et al. (2011). Effect of epidural stimulation of the lumbosacral spinal cord on voluntary movement, standing, and assisted stepping after motor complete paraplegia: a case study. Lancet 377, 1938–1947.10.1016/S0140-6736(11)60547-3Search in Google Scholar

Harkema, S.J., Hillyer, J., Schmidt-Read, M., Ardolino, E., Sisto, S.A., and Behrman, A.L. (2012). Locomotor training: as a treatment of spinal cord injury and in the progression of neurologic rehabilitation. Arch. Phys. Med. Rehabil. 93, 1588–1597.10.1016/j.apmr.2012.04.032Search in Google Scholar PubMed

Hicks, A.L. and Ginis, K.A. (2008). Treadmill training after spinal cord injury: it’s not just about the walking. J. Rehabil. Res. Dev. 45, 241–248.10.1682/JRRD.2007.02.0022Search in Google Scholar

Hugenholtz, H. (2003). Methylprednisolone for acute spinal cord injury: not a standard of care. CMAJ 168, 1145–1146.Search in Google Scholar

Hunter, J.P. and Ashby, P. (1994). Segmental effects of epidural spinal cord stimulation in humans. J. Physiol. 474, 407–419.10.1113/jphysiol.1994.sp020032Search in Google Scholar PubMed PubMed Central

Jackson, A. and Zimmermann, J.B. (2012). Neural interfaces for the brain and spinal cord—restoring motor function. Nat. Rev. Neurol. 8, 690–699.10.1038/nrneurol.2012.219Search in Google Scholar PubMed

Janatova, J. (2000). Activation and control of complement, inflammation, and infection associated with the use of biomedical polymers. ASAIO J. 46, S53–S62.10.1097/00002480-200011000-00038Search in Google Scholar PubMed

Ji, B., Li, M., Budel, S., Pepinsky, R.B., Walus, L., Engber, T.M., Strittmatter, S.M., and Relton, J.K. (2005). Effect of combined treatment with methylprednisolone and soluble Nogo-66 receptor after rat spinal cord injury. Eur. J. Neurosci. 22, 587–594.10.1111/j.1460-9568.2005.04241.xSearch in Google Scholar PubMed PubMed Central

Jimenez Hamann, M.C., Tator, C.H., and Shoichet, M.S. (2005). Injectable intrathecal delivery system for localized administration of EGF and FGF-2 to the injured rat spinal cord. Exp. Neurol. 194, 106–119.10.1016/j.expneurol.2005.01.030Search in Google Scholar PubMed

Kim, J.Y., Kim, S.J., and Bang, M. (2012). Spinal cord atrophy and early motor recovery following transverse myelitis in pediatric patients. Ann. Rehabil. Med. 36, 328–333.10.5535/arm.2012.36.3.328Search in Google Scholar PubMed PubMed Central

Kjell, J., Pernold, K., Olson, L., and Abrams, M.B. (2014). Oral erlotinib, but not rapamycin, causes modest acceleration of bladder and hindlimb recovery from spinal cord injury in rats. Spinal Cord 52, 186–190.10.1038/sc.2013.166Search in Google Scholar PubMed

Knikou, M. (2012). Plasticity of corticospinal neural control after locomotor training in human spinal cord injury. Neural Plast. 2012, 254948.10.1155/2012/254948Search in Google Scholar PubMed PubMed Central

Krassioukov, A. (2009). Autonomic function following cervical spinal cord injury. Respir. Physiol. Neurobiol. 169, 157–164.10.1016/j.resp.2009.08.003Search in Google Scholar PubMed

Kumru, H. and Kofler, M. (2012). Effect of spinal cord injury and of intrathecal baclofen on brainstem reflexes. Clin. Neurophysiol. 123, 45–53.10.1016/j.clinph.2011.06.036Search in Google Scholar PubMed

Lawrence, D.G. and Kuypers, H.G. (1968). The functional organization of the motor system in the monkey. I. The effects of bilateral pyramidal lesions. Brain 91, 1–14.10.1093/brain/91.1.1Search in Google Scholar PubMed

Lee, H.C., Cho, D.Y., Lee, W.Y., and Chuang, H.C. (2007). Pitfalls in treatment of acute cervical spinal cord injury using high-dose methylprednisolone: a retrospect audit of 111 patients. Surg. Neurol. 68, S37–S41.10.1016/j.surneu.2007.06.085Search in Google Scholar PubMed

Lo, A.C. and Triche, E.W. (2008). Improving gait in multiple sclerosis using robot-assisted, body weight supported treadmill training. Neurorehabil. Neural Repair 22, 661–671.10.1177/1545968308318473Search in Google Scholar PubMed

Lutton, C., Young, Y.W., Williams, R., Meedeniya, A.C., Mackay-Sim, A., and Goss, B. (2012). Combined VEGF and PDGF treatment reduces secondary degeneration after spinal cord injury. J. Neurotrauma 29, 957–970.10.1089/neu.2010.1423Search in Google Scholar PubMed

Marciniak, C., Rader, L., and Gagnon, C. (2008). The use of botulinum toxin for spasticity after spinal cord injury. Am. J. Phys. Med. Rehabil. 87, 312–317.10.1097/PHM.0b013e318168ceafSearch in Google Scholar PubMed

Martinez, M., Delivet-Mongrain, H., Leblond, H., and Rossignol, S. (2012). Effect of locomotor training in completely spinalized cats previously submitted to a spinal hemisection. J. Neurosci. 32, 10961–10970.10.1523/JNEUROSCI.1578-12.2012Search in Google Scholar PubMed PubMed Central

McDonald, J. (2008). Repairing the damaged spinal cord. Sci. Am. 65.Search in Google Scholar

McTigue, D.M., Horner, P.J., Stokes, B.T., and Gage, F.H. (1998). Neurotrophin-3 and brain-derived neurotrophic factor induce oligodendrocyte proliferation and myelination of regenerating axons in the contused adult rat spinal cord. J. Neurosci. 18, 5354–5365.10.1523/JNEUROSCI.18-14-05354.1998Search in Google Scholar

Mehrholz, J., Kugler, J., and Pohl, M. (2012). Locomotor training for walking after spinal cord injury. Cochrane Database Syst. Rev. 11, CD006676.10.1002/14651858.CD006676.pub3Search in Google Scholar PubMed

Middleton, J.W., Siddall, P.J., Walker, S., Molloy, A.R., and Rutkowski, S.B. (1996). Intrathecal clonidine and baclofen in the management of spasticity and neuropathic pain following spinal cord injury: a case study. Arch. Phys. Med. Rehabil. 77, 824–826.10.1016/S0003-9993(96)90264-6Search in Google Scholar

Mitsui, T., Shumsky, J.S., Lepore, A.C., Murray, M., and Fischer, I. (2005). Transplantation of neuronal and glial restricted precursors into contused spinal cord improves bladder and motor functions, decreases thermal hypersensitivity, and modifies intraspinal circuitry. J. Neurosci. 25, 9624–9636.10.1523/JNEUROSCI.2175-05.2005Search in Google Scholar PubMed PubMed Central

Mondello, S.E., Kasten, M.R., Horner, P.J., and Moritz, C.T. (2014). Therapeutic intraspinal stimulation to generate activity and promote long-term recovery. Front. Neurosci. 8, 21.10.3389/fnins.2014.00021Search in Google Scholar PubMed PubMed Central

Mountney, A., Zahner, M.R., Lorenzini, I., Oudega, M., Schramm, L.P., and Schnaar, R.L. (2010). Sialidase enhances recovery from spinal cord contusion injury. Proc. Natl. Acad. Sci. USA 107, 11561–11566.10.1073/pnas.1006683107Search in Google Scholar PubMed PubMed Central

Nance, P.W., Bugaresti, J., Shellenberger, K., Sheremata, W., and Martinez-Arizala, A. (1994). Efficacy and safety of tizanidine in the treatment of spasticity in patients with spinal cord injury. North American Tizanidine Study Group. Neurology 44, 44–51.Search in Google Scholar

Ogawa, Y., Sawamoto, K., Miyata, T., Miyao, S., Watanabe, M., Nakamura, M., Bregman, B.S., Koike, M., Uchiyama, Y., Toyama, Y., et al. (2002). Transplantation of in vitro-expanded fetal neural progenitor cells results in neurogenesis and functional recovery after spinal cord contusion injury in adult rats. J. Neurosci. Res. 69, 925–933.10.1002/jnr.10341Search in Google Scholar PubMed

Oudega, M. and Xu, X.M. (2006). Schwann cell transplantation for repair of the adult spinal cord. J. Neurotrauma 23, 453–467.10.1089/neu.2006.23.453Search in Google Scholar PubMed

Pearse, D.D., Marcillo, A.E., Oudega, M., Lynch, M.P., Wood, P.M., and Bunge, M.B. (2004). Transplantation of Schwann cells and olfactory ensheathing glia after spinal cord injury: does pretreatment with methylprednisolone and interleukin-10 enhance recovery? J. Neurotrauma 21, 1223–1239.10.1089/0897715041953876Search in Google Scholar

Popovic, M.R., Popovic, D.B., and Keller, T. (2002). Neuroprostheses for grasping. Neurol. Res. 24, 443–452.10.1179/016164102101200311Search in Google Scholar PubMed

Prochazka, A., Mushahwar, V.K., and McCreery, D.B. (2001). Neural prostheses. J. Physiol. 533, 99–109.10.1111/j.1469-7793.2001.0099b.xSearch in Google Scholar PubMed PubMed Central

Rabchevsky, A.G., and Kitzman, P.H. (2011). Latest approaches for the treatment of spasticity and autonomic dysreflexia in chronic spinal cord injury. Neurotherapeutics 8, 274–282.10.1007/s13311-011-0025-5Search in Google Scholar PubMed PubMed Central

Rabchevsky, A.G., Fugaccia, I., Turner, A.F., Blades, D.A., Mattson, M.P., and Scheff, S.W. (2000). Basic fibroblast growth factor (bFGF) enhances functional recovery following severe spinal cord injury to the rat. Exp. Neurol. 164, 280–291.10.1006/exnr.2000.7399Search in Google Scholar PubMed

Raineteau, O. and Schwab, M.E. (2001). Plasticity of motor systems after incomplete spinal cord injury. Nat. Rev. Neurosci. 2, 263–273.10.1038/35067570Search in Google Scholar PubMed

Rosenzweig, E.S., Courtine, G., Jindrich, D.L., Brock, J.H., Ferguson, A.R., Strand, S.C., Nout, Y.S., Roy, R.R., Miller, D.M., Beattie, M.S., et al. (2010). Extensive spontaneous plasticity of corticospinal projections after primate spinal cord injury. Nat. Neurosci. 13, 1505–1510.10.1038/nn.2691Search in Google Scholar PubMed PubMed Central

Saigal, R., Renzi, C., and Mushahwar, V.K. (2004). Intraspinal microstimulation generates functional movements after spinal-cord injury. IEEE Trans. Neural Syst. Rehabil. Eng. 12, 430–440.10.1109/TNSRE.2004.837754Search in Google Scholar PubMed

Sasaki, M., Hains, B.C., Lankford, K.L., Waxman, S.G., and Kocsis, J.D. (2006). Protection of corticospinal tract neurons after dorsal spinal cord transection and engraftment of olfactory ensheathing cells. Glia 53, 352–359.10.1002/glia.20285Search in Google Scholar PubMed PubMed Central

Sayenko, D.G., Angeli, C., Harkema, S.J., Edgerton, V.R., and Gerasimenko, Y.P. (2014). Neuromodulation of evoked muscle potentials induced by epidural spinal-cord stimulation in paralyzed individuals. J. Neurophysiol. 111, 1088–1099.10.1152/jn.00489.2013Search in Google Scholar PubMed PubMed Central

Sayer, F.T., Kronvall, E., and Nilsson, O.G. (2006). Methylprednisolone treatment in acute spinal cord injury: the myth challenged through a structured analysis of published literature. Spine J. 6, 335–343.10.1016/j.spinee.2005.11.001Search in Google Scholar PubMed

Seo, J.P. and Jang, S.H. (2015). Traumatic axonal injury of the corticospinal tract in the subcortical white matter in patients with mild traumatic brain injury. Brain Inj. 29, 110–114.10.3109/02699052.2014.973447Search in Google Scholar PubMed

Sharpe, A.N. and Jackson, A. (2014). Upper-limb muscle responses to epidural, subdural and intraspinal stimulation of the cervical spinal cord. J. Neural Eng. 11, 016005.10.1088/1741-2560/11/1/016005Search in Google Scholar PubMed PubMed Central

Song, X.Y., Li, F., Zhang, F.H., Zhong, J.H., and Zhou, X.F. (2008). Peripherally-derived BDNF promotes regeneration of ascending sensory neurons after spinal cord injury. PLoS One 3, e1707.10.1371/journal.pone.0001707Search in Google Scholar PubMed PubMed Central

Sun, T., Ye, C., Wu, J., Zhang, Z., Cai, Y., and Yue, F. (2013). Treadmill step training promotes spinal cord neural plasticity after incomplete spinal cord injury. Neural Regen. Res. 8, 2540–2547.Search in Google Scholar

Takami, T., Oudega, M., Bates, M.L., Wood, P.M., Kleitman, N., and Bunge, M.B. (2002). Schwann cell but not olfactory ensheathing glia transplants improve hindlimb locomotor performance in the moderately contused adult rat thoracic spinal cord. J. Neurosci. 22, 6670–6681.10.1523/JNEUROSCI.22-15-06670.2002Search in Google Scholar

Talbott, J.F., Cao, Q., Bertram, J., Nkansah, M., Benton, R.L., Lavik, E., and Whittemore, S.R. (2007). CNTF promotes the survival and differentiation of adult spinal cord-derived oligodendrocyte precursor cells in vitro but fails to promote remyelination in vivo. Exp. Neurol. 204, 485–489.10.1016/j.expneurol.2006.12.013Search in Google Scholar PubMed PubMed Central

Thuret, S., Moon, L.D., and Gage, F.H. (2006). Therapeutic interventions after spinal cord injury. Nat. Rev. Neurosci. 7, 628–643.10.1038/nrn1955Search in Google Scholar PubMed

Topka, H., Cohen, L.G., Cole, R.A., and Hallett, M. (1991). Reorganization of corticospinal pathways following spinal cord injury. Neurology 41, 1276–1283.10.1212/WNL.41.8.1276Search in Google Scholar

Tronnier, V. and Rasche, D. (2013). Epidural and subdural stimulation. Handb. Clin. Neurol. 116, 343–351.10.1016/B978-0-444-53497-2.00028-0Search in Google Scholar PubMed

van den Berg, M.E., Castellote, J.M., de Pedro-Cuesta, J., and Mahillo-Fernandez, I. (2010). Survival after spinal cord injury: a systematic review. J. Neurotrauma 27, 1517–1528.10.1089/neu.2009.1138Search in Google Scholar PubMed

Weaver, L.C., Gris, D., Saville, L.R., Oatway, M.A., Chen, Y., Marsh, D.R., Hamilton, E.F., and Dekaban, G.A. (2005). Methylprednisolone causes minimal improvement after spinal cord injury in rats, contrasting with benefits of an anti-integrin treatment. J. Neurotrauma 22, 1375–1387.10.1089/neu.2005.22.1375Search in Google Scholar PubMed

Weidner, N., Ner, A., Salimi, N., and Tuszynski, M.H. (2001). Spontaneous corticospinal axonal plasticity and functional recovery after adult central nervous system injury. Proc. Natl. Acad. Sci. USA 98, 3513–3518.10.1073/pnas.051626798Search in Google Scholar PubMed PubMed Central

West, C.R., Alyahya, A., Laher, I., and Krassioukov, A. (2013). Peripheral vascular function in spinal cord injury: a systematic review. Spinal Cord 51, 10–19.10.1038/sc.2012.136Search in Google Scholar PubMed

Wyndaele, M. and Wyndaele, J-J. (2006). Incidence, prevalence and epidemiology of spinal cord injury: what learns a worldwide literature survey? Spinal Cord 44, 523–529.10.1038/sj.sc.3101893Search in Google Scholar PubMed

Zhang, L., Ma, Z., Smith, G.M., Wen, X., Pressman, Y., Wood, P.M., and Xu, X.M. (2009). GDNF-enhanced axonal regeneration and myelination following spinal cord injury is mediated by primary effects on neurons. Glia 57, 1178–1191.10.1002/glia.20840Search in Google Scholar PubMed PubMed Central

Received: 2015-1-7
Accepted: 2015-1-26
Published Online: 2015-4-14
Published in Print: 2015-8-1

©2015 by De Gruyter

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