Neuroprotection in Spinal Cord Injury

  • Kewal K. Jain
Part of the Springer Protocols Handbooks book series (SPH)


Spinal cord injury (SCI) can lead to serious neurological disability and the most serious form of it is paraplegia or quadriplegia. The effects of SCI are extensive and adversely affect multiple organ systems including the sensorimotor, respiratory, gastrointestinal, urinary and reproductive systems. The psycho-social effects are devastating, and the financial burden associated with SCI is staggering. As a result of advances in critical care and rehabilitation, the life span of these patients has been extended to as much as 40 years post-injury. However, there is no therapeutic measure available currently that enhances functional recovery significantly.


  1. Abematsu M, Tsujimura K, Yamano M, et al. Neurons derived from transplanted neural stem cells restore disrupted neuronal circuitry in a mouse model of spinal cord injury. J Clin Invest 2010;120:3255–66.CrossRefGoogle Scholar
  2. Bilginer B, Onal MB, Narin F, et al. Antiapoptotic and neuroprotective effects of mycophenolate mofetil after acute spinal cord injury in young rats. Childs Nerv Syst 2009;25:1555–61.CrossRefGoogle Scholar
  3. Bradbury EJ, Carter LM. Manipulating the glial scar: Chondroitinase ABC as a therapy for spinal cord injury. Brain Res Bull 2011;84:306–16.CrossRefGoogle Scholar
  4. Buss A, Pech K, Kakulas BA, et al. Matrix metalloproteinases and their inhibitors in human traumatic spinal cord injury. BMC Neurology 2007;7:17.CrossRefGoogle Scholar
  5. Casha S, Zygun D, McGowan MD, et al. Results of a phase II placebo-controlled randomized trial of minocycline in acute spinal cord injury. Brain 2012;135(Pt 4):1224–36.CrossRefGoogle Scholar
  6. Chen G, Fang X, Yu M. Regulation of gene expression in rats with spinal cord injury based on microarray data. Mol Med Rep 2015;12:2465–72.CrossRefGoogle Scholar
  7. Deda H, Inci M, Kurekci A, et al. Treatment of chronic spinal cord injured patients with autologous bone marrow-derived hematopoietic stem cell transplantation: 1-year follow-up. Cytotherapy 2008;10:565–74.CrossRefGoogle Scholar
  8. Gensel JC, Wang Y, Guan Z, et al. Toll-like receptors and dectin-1, a C-type lectin receptor, trigger divergent functions in CNS macrophages. J Neurosci 2015;35:9966–76.CrossRefGoogle Scholar
  9. Hurlbert RJ, Hadley MN, Walters BC, et al. Pharmacological therapy for acute spinal cord injury. Neurosurgery 2015;76 Suppl 1:S71–83.CrossRefGoogle Scholar
  10. Jain KK. Hyperbaric oxygen therapy in neurosurgery. In, Jain KK. Textbook of Hyperbaric Medicine, 6th ed. Springer, New York 2017.CrossRefGoogle Scholar
  11. Kalayci M, Coskun O, Cagavi F, et al. Neuroprotective effects of ebselen on experimental spinal cord injury in rats. Neurochem Res 2005;30:403–10.CrossRefGoogle Scholar
  12. Li N, Leung GK. Oligodendrocyte Precursor Cells in Spinal Cord Injury: A Review and Update. Biomed Res Int 2015;2015:235195.PubMedPubMedCentralGoogle Scholar
  13. Ma YH, Zhang Y, Cao L, et al. Effect of neurotrophin-3 genetically modified olfactory ensheathing cells transplantation on spinal cord injury. Cell Transplant 2010;19:167–77.CrossRefGoogle Scholar
  14. Mackay-Sim A, Féron F, Cochrane J, et al. Autologous olfactory ensheathing cell transplantation in human paraplegia: a 3-year clinical trial. Brain 2008;131:2376–86.CrossRefGoogle Scholar
  15. McKerracher L, Anderson KD. Analysis of recruitment and outcomes in the phase I/IIa Cethrin clinical trial for acute spinal cord injury. J Neurotrauma 2013;30:1795–804.CrossRefGoogle Scholar
  16. Meletis K, Barnabé-Heider F, Carlén M, et al. Spinal cord injury reveals multilineage differentiation of ependymal cells. PLoS Biol 2008;6(7):e182.CrossRefGoogle Scholar
  17. Monaco EA 3rd, Weiner GM, Friedlander RM. Randomized-controlled trial of minocycline for spinal cord injury shows promise. Neurosurgery 2013;72:N17–9.CrossRefGoogle Scholar
  18. Morino T, Ogata T, Takeba J, Yamamoto H. Microglia inhibition is a target of mild hypothermic treatment after the spinal cord injury. Spinal Cord 2008;46:425–31.CrossRefGoogle Scholar
  19. Mountney A, Zahner MR, Lorenzini I, et al. Sialidase enhances recovery from spinal cord contusion injury. PNAS 2010;107:11561–6.CrossRefGoogle Scholar
  20. Naghdi M, Tiraihi T, Namin SA, et al. Transdifferentiation of bone marrow stromal cells into cholinergic neuronal phenotype: a potential source for cell therapy in spinal cord injury. Cytotherapy 2009;11:137–52.CrossRefGoogle Scholar
  21. Nishimura S, Sasaki T, Shimizu A, et al. Global gene expression analysis following spinal cord injury in non-human primates. Exp Neurol 2014;261:171–9.CrossRefGoogle Scholar
  22. Nori S, Ahuja CS, Fehlings MG. Translational Advances in the Management of Acute Spinal Cord Injury: What is New? What is Hot? Neurosurgery 2017;64(CN suppl 1):119–128.CrossRefGoogle Scholar
  23. Oh SK, Choi KH, Yoo JY, et al. A phase III clinical trial showing limited efficacy of autologous mesenchymal stem cell therapy for spinal cord injury. Neurosurgery 2016;78:436–47.CrossRefGoogle Scholar
  24. Park JH, Kim DY, Sung IY, et al. Long-term Results of Spinal Cord Injury Therapy Using Mesenchymal Stem Cells Derived From Bone Marrow in Humans. Neurosurgery 2012;70:1238–47.CrossRefGoogle Scholar
  25. Ronsyn MW, Daans J, Spaepen G, et al. Plasmid-based genetic modification of human bone marrow-derived stromal cells: analysis of cell survival and transgene expression after transplantation in rat spinal cord. BMC Biotechnology 2007;7:90.CrossRefGoogle Scholar
  26. Sakai K, Yamamoto A, Matsubara K, et al. Human dental pulp-derived stem cells promote locomotor recovery after complete transection of the rat spinal cord by multiple neuro-regenerative mechanisms. J Clin Invest 2012;122:80–90.PubMedGoogle Scholar
  27. Sharp J, Frame J, Siegenthaler M, et al. Human embryonic Stem Cell-Derived Oligodendrocyte Progenitor Cell Transplants Improve Recovery after Cervical Spinal Cord Injury. Stem Cells 2010;28:152–63.Google Scholar
  28. Snyder EY, Teng YD. Stem Cells and Spinal Cord Repair. N Engl J Med 2012;366:1940–42.CrossRefGoogle Scholar
  29. 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.CrossRefGoogle Scholar
  30. Tator CH, Hashimoto R, Raich A, et al. Translational potential of preclinical trials of neuroprotection through pharmacotherapy for spinal cord injury. J Neurosurg Spine 2012;17(1 Suppl):157–229.CrossRefGoogle Scholar
  31. Tong J, Ren Y, Wang X, et al. Assessment of Nogo-66 receptor 1 function in vivo after spinal cord injury. Neurosurgery 2014;75:51–60.CrossRefGoogle Scholar
  32. Tsuji O, Miura K, Okada Y, et al. Therapeutic potential of appropriately evaluated safe-induced pluripotent stem cells for spinal cord injury. Proc Natl Acad Sci U S A 2010;107:12704–9.CrossRefGoogle Scholar
  33. Wu JC, Huang WC, Tsai YA, et al. Nerve repair using acidic fibroblast growth factor in human cervical spinal cord injury: a preliminary Phase I clinical study. J Neurosurg Spine 2008;8:208–214.CrossRefGoogle Scholar
  34. Yan J, Xu L, Welsh AM, et al. Extensive Neuronal Differentiation of Human Neural Stem Cell Grafts in Adult Rat Spinal Cord. PLoS Med 2007;4:e39.CrossRefGoogle Scholar
  35. Yeo JE, Kim JH, Kang SK. Selenium attenuates ROS-mediated apoptotic cell death of injured spinal cord through prevention of mitochondria dysfunction; in vitro and in vivo study. Cell Physiol Biochem 2008;21(1–3):225–38.CrossRefGoogle Scholar
  36. Zhang J, Zhang A, Sun Y, et al. Treatment with immunosuppressants FTY720 and tacrolimus promotes functional recovery after spinal cord injury in rats. Tohoku J Exp Med 2009;219:295–302.CrossRefGoogle Scholar
  37. Zhou Z, Peng X, Insolera R, et al. IL-10 promotes neuronal survival following spinal cord injury. Exp Neurol 2009;220:183–90.CrossRefGoogle Scholar
  38. Zhou Y, Wang Z, Li J, et al. Fibroblast growth factors in the management of spinal cord injury. J Cell Mol Med 2018;22:25–37.CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Kewal K. Jain
    • 1
  1. 1.Jain PharmaBiotechBaselSwitzerland

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