Neurochemical Research

, Volume 38, Issue 5, pp 895–905 | Cite as

Spinal Cord Injury: A Review of Current Therapy, Future Treatments, and Basic Science Frontiers

  • Abhay K. Varma
  • Arabinda Das
  • Gerald WallaceIV
  • John Barry
  • Alexey A. Vertegel
  • Swapan K. Ray
  • Naren L. Banik
Overview

Abstract

The incidence of acute and chronic spinal cord injury (SCI) in the United States is more than 10,000 per year, resulting in 720 cases per million persons enduring permanent disability each year. The economic impact of SCI is estimated to be more than 4 billion dollars annually. Preclinical studies, case reports, and small clinical trials suggest that early treatment may improve neurological recovery. To date, no proven therapeutic modality exists that has demonstrated a positive effect on neurological outcome. Emerging data from recent preclinical and clinical studies offer hope for this devastating condition. This review gives an overview of current basic research and clinical studies for the treatment of SCI.

Keywords

Spinal cord injury Clinical Preclinical 

Notes

Acknowledgments

Completion of this project was made possible by funding from the National Institutes of Neurological Disorders and Stroke (NS-31622, NS-38146, and NS-41088), the South Carolina Spinal Cord Injury Research Fund (SCSCIRF), and Department of Neurosciences (Neurosurgery). Authors thank Casey Holmes for help with the preparation of this manuscript.

References

  1. 1.
    Bracken MB (2012) Steroids for acute spinal cord injury. Cochrane Database Syst Rev 1:CD001046Google Scholar
  2. 2.
    Budh CN, Osteraker AL (2007) Life satisfaction in individuals with a spinal cord injury and pain. Clin Rehabil 21(1):89–96PubMedCrossRefGoogle Scholar
  3. 3.
    Farooqui (2010) Neurochemical aspects of spinal cord injury. In: Farooqui AA (ed) Neurochemical aspects of neurotraumatic and neurodegenerative diseases. Springer, Berlin, pp 107–142Google Scholar
  4. 4.
    Kiser TS Predicting outcome (prognosis) in spinal cord injury. In: Comission ASC (ed). http://www.spinalcord.ar.gov/Resources/Prognosis%20Fact%20Sheet.pdf2010.
  5. 5.
    Dumont RJ, Okonkwo DO, Verma S et al (2001) Acute spinal cord injury, part I: pathophysiologic mechanisms. Clin Neuropharmacol 24(5):254–264PubMedCrossRefGoogle Scholar
  6. 6.
    Guly HR, Bouamra O, Lecky FE (2008) The incidence of neurogenic shock in patients with isolated spinal cord injury in the emergency department. Resuscitation 76(1):57–62PubMedCrossRefGoogle Scholar
  7. 7.
    Bracken MB, Collins WF, Freeman DF et al (1984) Efficacy of methylprednisolone in acute spinal cord injury. JAMA, J Am Med Assoc 251(1):45–52CrossRefGoogle Scholar
  8. 8.
    Bracken MB, Shepard MJ, Collins WF Jr et al (1992) Methylprednisolone or naloxone treatment after acute spinal cord injury: 1-year follow-up data. Results of the second national acute spinal cord injury study. J Neurosurg 76(1):23–31PubMedCrossRefGoogle Scholar
  9. 9.
    Bracken MB, Shepard MJ, Collins WF et al (1990) A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the second national acute spinal cord injury study. New Engl J Med 322(20):1405–1411PubMedCrossRefGoogle Scholar
  10. 10.
    Tator CH (2006) Review of treatment trials in human spinal cord injury: issues, difficulties, and recommendations. Neurosurgery 59(5):957–982; discussion 982–957Google Scholar
  11. 11.
    Chvatal SA, Kim YT, Bratt-Leal AM, Lee H, Bellamkonda RV (2008) Spatial distribution and acute anti-inflammatory effects of methylprednisolone after sustained local delivery to the contused spinal cord. Biomaterials 29(12):1967–1975PubMedCrossRefGoogle Scholar
  12. 12.
    Das A, Smith JA, Gibson C, Varma AK, Ray SK, Banik NL (2011) Estrogen receptor agonists and estrogen attenuate TNF-alpha-induced apoptosis in VSC4.1 motoneurons. J Endocrinol 208(2):171–182PubMedCrossRefGoogle Scholar
  13. 13.
    Sribnick EA, Wingrave JM, Matzelle DD, Wilford GG, Ray SK, Banik NL (2005) Estrogen attenuated markers of inflammation and decreased lesion volume in acute spinal cord injury in rats. J Neurosci Res 82(2):283–293PubMedCrossRefGoogle Scholar
  14. 14.
    Wingrave JM, Schaecher KE, Sribnick EA et al (2003) Early induction of secondary injury factors causing activation of calpain and mitochondria-mediated neuronal apoptosis following spinal cord injury in rats. J Neurosci Res 73(1):95–104PubMedCrossRefGoogle Scholar
  15. 15.
    Bains M, Hall ED (2012) Antioxidant therapies in traumatic brain and spinal cord injury. Biochim Biophys Acta 1822(5):675–684PubMedCrossRefGoogle Scholar
  16. 16.
    Robert AA, Zamzami M, Sam AE (2012) Al Jadid M, Al Mubarak S. The efficacy of antioxidants in functional recovery of spinal cord injured rats: an experimental study. Neurol Sci 33(4):785–791PubMedCrossRefGoogle Scholar
  17. 17.
    Samantaray S, Sribnick EA, Das A et al (2008) Melatonin attenuates calpain upregulation, axonal damage and neuronal death in spinal cord injury in rats. J Pineal Res 44(4):348–357PubMedCrossRefGoogle Scholar
  18. 18.
    Mazzone GL, Nistri A (2011) Delayed neuroprotection by riluzole against excitotoxic damage evoked by kainate on rat organotypic spinal cord cultures. Neuroscience 190:318–327PubMedCrossRefGoogle Scholar
  19. 19.
    Rong W, Wang J, Liu X et al (2012) 17beta-estradiol attenuates neural cell apoptosis through inhibition of JNK phosphorylation in SCI rats and excitotoxicity induced by glutamate in vitro. Int J Neurosci 122(7):381–387PubMedCrossRefGoogle Scholar
  20. 20.
    Lutton C, Young YW, Williams R, Meedeniya AC, Mackay-Sim A, Goss B (2012) Combined VEGF and PDGF treatment reduces secondary degeneration after spinal cord injury. J Neurotrauma 29(5):957–970PubMedCrossRefGoogle Scholar
  21. 21.
    Ritz MF, Graumann U, Gutierrez B, Hausmann O (2010) Traumatic spinal cord injury alters angiogenic factors and TGF-beta1 that may affect vascular recovery. Curr Neurovasc Res 7(4):301–310PubMedCrossRefGoogle Scholar
  22. 22.
    Ray SK, Matzelle DD, Sribnick EA, Guyton MK, Wingrave JM, Banik NL (2003) Calpain inhibitor prevented apoptosis and maintained transcription of proteolipid protein and myelin basic protein genes in rat spinal cord injury. J Chem Neuroanat 26(2):119–124PubMedCrossRefGoogle Scholar
  23. 23.
    Ray SK, Samantaray S, Smith JA, Matzelle DD, Das A, Banik NL (2011) Inhibition of cysteine proteases in acute and chronic spinal cord injury. Neurotherapeutics 8(2):180–186PubMedCrossRefGoogle Scholar
  24. 24.
    Sribnick EA, Matzelle DD, Banik NL, Ray SK (2007) Direct evidence for calpain involvement in apoptotic death of neurons in spinal cord injury in rats and neuroprotection with calpain inhibitor. Neurochem Res 32(12):2210–2216PubMedCrossRefGoogle Scholar
  25. 25.
    Guha A, Tator CH, Piper I (1987) Effect of a calcium channel blocker on posttraumatic spinal cord blood flow. J Neurosurg 66(3):423–430PubMedCrossRefGoogle Scholar
  26. 26.
    Das A, McDowell M, Pava MJ, Smith JA, Reiter RJ, Woodward JJ, Varma AK, Ray SK, Banik NL (2010) The inhibition of apoptosis by melatonin in VSC4.1 motoneurons exposed to oxidative stress, glutamate excitotoxicity, or TNF-alpha toxicity involves membrane melatonin receptors. J Pineal Res 48(2):157–169PubMedCrossRefGoogle Scholar
  27. 27.
    Ray SK, Hogan EL, Banik NL (2003) Calpain in the pathophysiology of spinal cord injury: neuroprotection with calpain inhibitors. Brain Res Rev 42(2):169–185PubMedCrossRefGoogle Scholar
  28. 28.
    Samantaray S, Sribnick EA, Das A et al (2010) Neuroprotective efficacy of estrogen in experimental spinal cord injury in rats. Ann N Y Acad Sci 1199:90–94PubMedCrossRefGoogle Scholar
  29. 29.
    Lee JY, Choi SY, Oh TH, Yune TY (2012) 17beta-estradiol inhibits apoptotic cell death of oligodendrocytes by inhibiting rhoA-JNK3 activation after spinal cord injury. Endocrinology 153(8):3815–3827PubMedCrossRefGoogle Scholar
  30. 30.
    Samantaray S, Smith JA, Das A et al (2011) Low dose estrogen prevents neuronal degeneration and microglial reactivity in an acute model of spinal cord injury: effect of dosing, route of administration, and therapy delay. Neurochem Res 36(10):1809–1816PubMedCrossRefGoogle Scholar
  31. 31.
    Wang YF, Fan ZK, Cao Y, Yu DS, Zhang YQ, Wang YS (2011) 2-Methoxyestradiol inhibits the up-regulation of AQP4 and AQP1 expression after spinal cord injury. Brain Res 1370:220–226PubMedCrossRefGoogle Scholar
  32. 32.
    Bonnefont-Rousselot D, Collin F, Jore D, Gardes-Albert M (2011) Reaction mechanism of melatonin oxidation by reactive oxygen species in vitro. J Pineal Res 50(3):328–335PubMedCrossRefGoogle Scholar
  33. 33.
    Wu UI, Mai FD, Sheu JN et al (2011) Melatonin inhibits microglial activation, reduces pro-inflammatory cytokine levels, and rescues hippocampal neurons of adult rats with acute Klebsiella pneumoniae meningitis. J Pineal Res 50(2):159–170PubMedGoogle Scholar
  34. 34.
    Das A, Wallace IV G, Reiter RJ, et al (2013) Overexpression of melatonin membrane receptors increases calcium-binding proteins and protects VSC4.1 motoneurons from glutamate toxicity through multiple mechanisms. J Pineal Res 54:58–68Google Scholar
  35. 35.
    Borisoff JF, Chan CC, Hiebert GW et al (2003) Suppression of Rho-kinase activity promotes axonal growth on inhibitory CNS substrates. Mol Cell Neurosci 22(3):405–416PubMedCrossRefGoogle Scholar
  36. 36.
    Ferrari G, Fabris M, Gorio A (1983) Gangliosides enhance neurite outgrowth in PC12 cells. Brain Res 284(2–3):215–221PubMedGoogle Scholar
  37. 37.
    Gonzenbach RR, Schwab ME (2008) Disinhibition of neurite growth to repair the injured adult CNS: focusing on Nogo. Cell Mol Life Sci 65(1):161–176PubMedCrossRefGoogle Scholar
  38. 38.
    Gorio A, Ferrari G, Fusco M, Janigro D, Zanoni R, Jonsson G (1984) Gangliosides and their effects on rearranging peripheral and central neural pathways. Cent Nerv Syst Trauma 1(1):29–37Google Scholar
  39. 39.
    Liu BP, Cafferty WB, Budel SO, Strittmatter SM (2006) Extracellular regulators of axonal growth in the adult central nervous system. Philos Trans R Soc Lond B Biol Sci 361(1473):1593–1610PubMedCrossRefGoogle Scholar
  40. 40.
    Schwab ME (2004) Nogo and axon regeneration. Curr Opin Neurobiol 14(1):118–124PubMedCrossRefGoogle Scholar
  41. 41.
    Yiu G, He Z (2006) Glial inhibition of CNS axon regeneration. Nat Rev Neurosci 7(8):617–627PubMedCrossRefGoogle Scholar
  42. 42.
    Karimi-Abdolrezaee S, Billakanti R (2012) Reactive astrogliosis after spinal cord injury-beneficial and detrimental effects. Mol Neurobiol 46(2):251–264PubMedCrossRefGoogle Scholar
  43. 43.
    Dergham P, Ellezam B, Essagian C, Avedissian H, Lubell WD, McKerracher L (2002) Rho signaling pathway targeted to promote spinal cord repair. J Neurosci 22(15):6570–6577PubMedGoogle Scholar
  44. 44.
    Dubreuil CI, Winton MJ, McKerracher L (2003) Rho activation patterns after spinal cord injury and the role of activated Rho in apoptosis in the central nervous system. J Cell Biol 162(2):233–243PubMedCrossRefGoogle Scholar
  45. 45.
    Jalink K, van Corven EJ, Hengeveld T, Morii N, Narumiya S, Moolenaar WH (1994) Inhibition of lysophosphatidate- and thrombin-induced neurite retraction and neuronal cell rounding by ADP ribosylation of the small GTP-binding protein Rho. J Cell Biol 126(3):801–810PubMedCrossRefGoogle Scholar
  46. 46.
    Lord-Fontaine S, Yang F, Diep Q et al (2008) Local inhibition of Rho signaling by cell-permeable recombinant protein BA-210 prevents secondary damage and promotes functional recovery following acute spinal cord injury. J Neurotrauma 25(11):1309–1322PubMedCrossRefGoogle Scholar
  47. 47.
    Sung JK, Miao L, Calvert JW, Huang L, Louis Harkey H, Zhang JH (2003) A possible role of RhoA/Rho-kinase in experimental spinal cord injury in rat. Brain Res 959(1):29–38PubMedCrossRefGoogle Scholar
  48. 48.
    Gu YL, Yin LW, Zhang Z et al (2012) Neurotrophin expressions in neural stem cells grafted acutely to transected spinal cord of adult rats linked to functional improvement. Cell Mol Neurobiol 32(7):1089–1097PubMedCrossRefGoogle Scholar
  49. 49.
    Quertainmont R, Cantinieaux D, Botman O, Sid S, Schoenen J, Franzen R (2012) Mesenchymal stem cell graft improves recovery after spinal cord injury in adult rats through neurotrophic and pro-angiogenic actions. PLoS One 7(6):e39500PubMedCrossRefGoogle Scholar
  50. 50.
    Uchida K, Nakajima H, Hirai T et al (2012) The retrograde delivery of adenovirus vector carrying the gene for brain-derived neurotrophic factor protects neurons and oligodendrocytes from apoptosis in the chronically compressed spinal cord of twy/twy mice. Spine 37(26):2125–2135PubMedCrossRefGoogle Scholar
  51. 51.
    Donnelly EM, Lamanna J, Boulis NM (2012) Stem cell therapy for the spinal cord. Stem Cell Res Ther 3(4):24PubMedCrossRefGoogle Scholar
  52. 52.
    Wang H, Fang H, Dai J, Liu G, Xu ZJ (2013) Induced pluripotent stem cells for spinal cord injury therapy: current status and perspective. Neurol Sci 34(1):11–17PubMedCrossRefGoogle Scholar
  53. 53.
    Reddy MK, Wu L, Kou W, Ghorpade A, Labhasetwar V (2008) Superoxide dismutase-loaded PLGA nanoparticles protect cultured human neurons under oxidative stress. Appl Biochem Biotechnol 151(2–3):565–577PubMedCrossRefGoogle Scholar
  54. 54.
    Vertegel AA, Reukov V, Maximov V (2011) Enzyme-nanoparticle conjugates for biomedical applications. Methods Mol Biol 679:165–182PubMedCrossRefGoogle Scholar
  55. 55.
    Sharma HS (2008) New perspectives for the treatment options in spinal cord injury. Expert Opin Pharmacother 9(16):2773–2800PubMedCrossRefGoogle Scholar
  56. 56.
    Begley DJ (2004) Delivery of therapeutic agents to the central nervous system: the problems and the possibilities. Pharmacol Ther 104(1):29–45PubMedCrossRefGoogle Scholar
  57. 57.
    Schroeder U, Sommerfeld P, Ulrich S, Sabel BA (1998) Nanoparticle technology for delivery of drugs across the blood-brain barrier. J Pharm Sci 87(11):1305–1307PubMedCrossRefGoogle Scholar
  58. 58.
    Torchilin VP (2000) Drug targeting. Eur J Pharm Sci 11(Suppl 2):S81–91PubMedCrossRefGoogle Scholar
  59. 59.
    Kreuter J (2001) Nanoparticulate systems for brain delivery of drugs. Adv Drug Deliv Rev 47(1):65–81PubMedCrossRefGoogle Scholar
  60. 60.
    Lin Y, Pan Y, Shi Y, Huang X, Jia N, Jiang JY (2012) Delivery of large molecules via poly(butyl cyanoacrylate) nanoparticles into the injured rat brain. Nanotechnology 23(16):165101Google Scholar
  61. 61.
    Kreuter J, Ramge P, Petrov V et al (2003) Direct evidence that polysorbate-80-coated poly(butylcyanoacrylate) nanoparticles deliver drugs to the CNS via specific mechanisms requiring prior binding of drug to the nanoparticles. Pharm Res 20(3):409–416PubMedCrossRefGoogle Scholar
  62. 62.
    Kurakhmaeva KB, Djindjikhashvili IA, Petrov VE et al (2009) Brain targeting of nerve growth factor using poly(butyl cyanoacrylate) nanoparticles. J Drug Target 17(8):564–574PubMedCrossRefGoogle Scholar
  63. 63.
    Sharma HS, Ali S, Tian ZR et al (2009) Nano-drug delivery and neuroprotection in spinal cord injury. J Nanosci Nanotechnol 9(8):5014–5037PubMedCrossRefGoogle Scholar
  64. 64.
    Gibaud S, Demoy M, Andreux JP, Weingarten C, Gouritin B, Couvreur P (1996) Cells involved in the capture of nanoparticles in hematopoietic organs. J Pharm Sci 85(9):944–950PubMedCrossRefGoogle Scholar
  65. 65.
    Moghimi SM, Hunter AC (2001) Capture of stealth nanoparticles by the body’s defences. Crit Rev Ther Drug Carrier Syst 18(6):527–550PubMedCrossRefGoogle Scholar
  66. 66.
    Kang CE, Baumann MD, Tator CH, Shoichet MS. Localized and sustained delivery of fibroblast growth factor-2 from a nanoparticle-hydrogel composite for treatment of spinal cord injury. Cells Tissues Organs. Jul 13 2012Google Scholar
  67. 67.
    Cho Y, Shi R, Ivanisevic A, Borgens RB (2010) Functional silica nanoparticle-mediated neuronal membrane sealing following traumatic spinal cord injury. J Neurosci Res 88(7):1433–1444PubMedCrossRefGoogle Scholar
  68. 68.
    Wang YT, Lu XM, Zhu F et al (2011) The use of a gold nanoparticle-based adjuvant to improve the therapeutic efficacy of hNgR-Fc protein immunization in spinal cord-injured rats. Biomaterials 32(31):7988–7998PubMedCrossRefGoogle Scholar
  69. 69.
    Xia T, Kovochich M, Brant J et al (2006) Comparison of the abilities of ambient and manufactured nanoparticles to induce cellular toxicity according to an oxidative stress paradigm. Nano Lett 6(8):1794–1807PubMedCrossRefGoogle Scholar
  70. 70.
    Hall ED, Braughler JM (1982) Glucocorticoid mechanisms in acute spinal cord injury: a review and therapeutic rationale. Surg Neurol 18(5):320–327PubMedCrossRefGoogle Scholar
  71. 71.
    Bracken MB, Shepard MJ, Holford TR et al (1998) Methylprednisolone or tirilazad mesylate administration after acute spinal cord injury: 1-year follow up. Results of the third national acute spinal cord injury randomized controlled trial. J Neurosurg 89(5):699–706PubMedCrossRefGoogle Scholar
  72. 72.
    Braughler JM, Hall ED (1983) Lactate and pyruvate metabolism in injured cat spinal cord before and after a single large intravenous dose of methylprednisolone. J Neurosurg 59(2):256–261PubMedCrossRefGoogle Scholar
  73. 73.
    Faden AI, Jacobs TP, Mougey E, Holaday JW (1981) Endorphins in experimental spinal injury: therapeutic effect of naloxone. Ann Neurol 10(4):326–332PubMedCrossRefGoogle Scholar
  74. 74.
    Coleman WP, Benzel D, Cahill DW et al (2000) A critical appraisal of the reporting of the national acute spinal cord injury studies (II and III) of methylprednisolone in acute spinal cord injury. J Spinal Disord 13(3):185–199PubMedCrossRefGoogle Scholar
  75. 75.
    Hurlbert RJ (2001) The role of steroids in acute spinal cord injury: an evidence-based analysis. Spine 26(24 Suppl):S39–46PubMedCrossRefGoogle Scholar
  76. 76.
    Qian T, Guo X, Levi AD, Vanni S, Shebert RT, Sipski ML (2005) High-dose methylprednisolone may cause myopathy in acute spinal cord injury patients. Spinal Cord 43(4):199–203PubMedCrossRefGoogle Scholar
  77. 77.
    Anderson DK, Braughler JM, Hall ED, Waters TR, McCall JM, Means ED (1988) Effects of treatment with U-74006F on neurological outcome following experimental spinal cord injury. J Neurosurg 69(4):562–567PubMedCrossRefGoogle Scholar
  78. 78.
    Fehlings MG, Tator CH, Linden RD (1989) The effect of nimodipine and dextran on axonal function and blood flow following experimental spinal cord injury. J Neurosurg 71(3):403–416PubMedCrossRefGoogle Scholar
  79. 79.
    Haghighi SS, Stiens T, Oro JJ, Madsen R (1993) Evaluation of the calcium channel antagonist nimodipine after experimental spinal cord injury. Surg Neurol 39(5):403–408PubMedCrossRefGoogle Scholar
  80. 80.
    Ross IB, Tator CH (1991) Further studies of nimodipine in experimental spinal cord injury in the rat. J Neurotrauma 8(4):229–238PubMedCrossRefGoogle Scholar
  81. 81.
    Pointillart V, Petitjean ME, Wiart L et al (2000) Pharmacological therapy of spinal cord injury during the acute phase. Spinal Cord 38(2):71–76PubMedCrossRefGoogle Scholar
  82. 82.
    Gaviria M, Privat A, d’Arbigny P, Kamenka J, Haton H, Ohanna F (2000) Neuroprotective effects of a novel NMDA antagonist, Gacyclidine, after experimental contusive spinal cord injury in adult rats. Brain Res 874(2):200–209PubMedCrossRefGoogle Scholar
  83. 83.
    Gaviria M, Privat A, d’Arbigny P, Kamenka JM, Haton H, Ohanna F (2000) Neuroprotective effects of gacyclidine after experimental photochemical spinal cord lesion in adult rats: dose-window and time-window effects. J Neurotrauma 17(1):19–30PubMedCrossRefGoogle Scholar
  84. 84.
    Fehlings MG, Baptiste DC (2005) Current status of clinical trials for acute spinal cord injury. Injury 36(Suppl 2):B113–122PubMedCrossRefGoogle Scholar
  85. 85.
    Monga V, Meena CL, Kaur N, Jain R (2008) Chemistry and biology of thyrotropin-releasing hormone (TRH) and its analogs. Curr Med Chem 15(26):2718–2733PubMedCrossRefGoogle Scholar
  86. 86.
    Naftchi NE (1982) Prevention of damage in acute spinal cord injury by peptides and pharmacologic agents. Peptides 3(3):235–247PubMedCrossRefGoogle Scholar
  87. 87.
    Faden AI, Jacobs TP, Smith MT (1984) Thyrotropin-releasing hormone in experimental spinal injury: dose response and late treatment. Neurology 34(10):1280–1284PubMedCrossRefGoogle Scholar
  88. 88.
    Pitts LH, Ross A, Chase GA, Faden AI (1995) Treatment with thyrotropin-releasing hormone (TRH) in patients with traumatic spinal cord injuries. J Neurotrauma 12(3):235–243PubMedCrossRefGoogle Scholar
  89. 89.
    Ledeen RW (1978) Ganglioside structures and distribution: are they localized at the nerve ending? J Supramol Struct 8(1):1–17PubMedCrossRefGoogle Scholar
  90. 90.
    Sabel BA, Slavin MD, Stein DG (1984) GM1 ganglioside treatment facilitates behavioral recovery from bilateral brain damage. Science 225(4659):340–342PubMedCrossRefGoogle Scholar
  91. 91.
    Sabel BA, DelMastro R, Dunbar GL, Stein DG (1987) Reduction of anterograde degeneration in brain damaged rats by GM1-gangliosides. Neurosci Lett 77(3):360–366PubMedCrossRefGoogle Scholar
  92. 92.
    Cuello AC, Stephens PH, Tagari PC, Sofroniew MV, Pearson RC (1986) Retrograde changes in the nucleus basalis of the rat, caused by cortical damage, are prevented by exogenous ganglioside GM1. Brain Res 376(2):373–377PubMedCrossRefGoogle Scholar
  93. 93.
    Geisler FH, Dorsey FC, Coleman WP (1991) Recovery of motor function after spinal-cord injury–a randomized, placebo-controlled trial with GM-1 ganglioside. New Engl J Med 324(26):1829–1838PubMedCrossRefGoogle Scholar
  94. 94.
    Geisler FH, Coleman WP, Grieco G, Poonian D (2001) The Sygen multicenter acute spinal cord injury study. Spine 26(24 Suppl):S87–98PubMedCrossRefGoogle Scholar
  95. 95.
    Geisler FH, Coleman WP, Grieco G, Poonian D (2001) Measurements and recovery patterns in a multicenter study of acute spinal cord injury. Spine 26(24 Suppl):S68–86PubMedCrossRefGoogle Scholar
  96. 96.
    Geisler FH, Coleman WP, Grieco G, Poonian D (2001) Recruitment and early treatment in a multicenter study of acute spinal cord injury. Spine 26(24 Suppl):S58–67PubMedCrossRefGoogle Scholar
  97. 97.
    Chinnock P, Roberts I (2005) Gangliosides for acute spinal cord injury. Cochrane Database Syst Rev 2:CD004444Google Scholar
  98. 98.
    Fehlings MG, Theodore N, Harrop J et al (2011) A phase I/IIa clinical trial of a recombinant Rho protein antagonist in acute spinal cord injury. J Neurotrauma 28(5):787–796PubMedCrossRefGoogle Scholar
  99. 99.
    Liebscher T, Schnell L, Schnell D et al (2005) Nogo-A antibody improves regeneration and locomotion of spinal cord-injured rats. Ann Neurol 58(5):706–719PubMedCrossRefGoogle Scholar
  100. 100.
    Freund P, Schmidlin E, Wannier T et al (2006) Nogo-A-specific antibody treatment enhances sprouting and functional recovery after cervical lesion in adult primates. Nat Med 12(7):790–792PubMedCrossRefGoogle Scholar
  101. 101.
    Zorner B, Schwab ME (2010) Anti-Nogo on the go: from animal models to a clinical trial. Ann N Y Acad Sci 1198(Suppl 1):E22–34PubMedCrossRefGoogle Scholar
  102. 102.
    Cheng H, Cao Y, Olson L (1996) Spinal cord repair in adult paraplegic rats: partial restoration of hind limb function. Science 273(5274):510–513PubMedCrossRefGoogle Scholar
  103. 103.
    Cheng H, Liao KK, Liao SF, Chuang TY, Shih YH (2004) Spinal cord repair with acidic fibroblast growth factor as a treatment for a patient with chronic paraplegia. Spine 29(14):E284–288PubMedCrossRefGoogle Scholar
  104. 104.
    Wu JC, Huang WC, Chen YC et al (2011) Acidic fibroblast growth factor for repair of human spinal cord injury: a clinical trial. J Neurosurg Spine 15(3):216–227PubMedCrossRefGoogle Scholar
  105. 105.
    Bomstein Y, Marder JB, Vitner K et al (2003) Features of skin-coincubated macrophages that promote recovery from spinal cord injury. J Neuroimmunol 142(1–2):10–16PubMedCrossRefGoogle Scholar
  106. 106.
    Knoller N, Auerbach G, Fulga V et al (2005) Clinical experience using incubated autologous macrophages as a treatment for complete spinal cord injury: phase I study results. J Neurosurg Spine 3(3):173–181PubMedCrossRefGoogle Scholar
  107. 107.
    Schwartz M, Yoles E (2005) Macrophages and dendritic cells treatment of spinal cord injury: from the bench to the clinic. Acta Neurochir 93:147–150CrossRefGoogle Scholar
  108. 108.
    Caplan AI (2007) Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J Cell Physiol 213(2):341–347PubMedCrossRefGoogle Scholar
  109. 109.
    Sykova E, Homola A, Mazanec R et al (2006) Autologous bone marrow transplantation in patients with subacute and chronic spinal cord injury. Cell Transplant 15(8–9):675–687PubMedCrossRefGoogle Scholar
  110. 110.
    Deda H, Inci MC, Kurekci AE et al (2008) Treatment of chronic spinal cord injured patients with autologous bone marrow-derived hematopoietic stem cell transplantation: 1-year follow-up. Cytotherapy 10(6):565–574PubMedCrossRefGoogle Scholar
  111. 111.
    Kumar AA, Kumar SR, Narayanan R, Arul K, Baskaran M (2009) Autologous bone marrow derived mononuclear cell therapy for spinal cord injury: a Phase I/II clinical safety and primary efficacy data. Exp Clin Transplant 7(4):241–248PubMedGoogle Scholar
  112. 112.
    Kishk NA, Gabr H, Hamdy S et al (2010) Case control series of intrathecal autologous bone marrow mesenchymal stem cell therapy for chronic spinal cord injury. Neurorehabil Neural Repair 24(8):702–708PubMedCrossRefGoogle Scholar
  113. 113.
    Huard JM, Youngentob SL, Goldstein BJ, Luskin MB, Schwob JE (1998) Adult olfactory epithelium contains multipotent progenitors that give rise to neurons and non-neural cells. J Comp Neurol 400(4):469–486PubMedCrossRefGoogle Scholar
  114. 114.
    Li Y, Field PM, Raisman G (1998) Regeneration of adult rat corticospinal axons induced by transplanted olfactory ensheathing cells. J Neurosci 18(24):10514–10524PubMedGoogle Scholar
  115. 115.
    Lima C, Escada P, Pratas-Vital J et al (2010) Olfactory mucosal autografts and rehabilitation for chronic traumatic spinal cord injury. Neurorehabil Neural repair 24(1):10–22PubMedCrossRefGoogle Scholar
  116. 116.
    Das A, Sribnick EA, Wingrave JM et al (2005) Calpain activation in apoptosis of ventral spinal cord 4.1 (VSC4.1) motoneurons exposed to glutamate: calpain inhibition provides functional neuroprotection. J Neurosci Res 81(4):551–562PubMedCrossRefGoogle Scholar
  117. 117.
    Ray SK, Wilford GG, Matzelle DC, Hogan EL, Banik NL (1999) Calpeptin and methylprednisolone inhibit apoptosis in rat spinal cord injury. Ann N Y Acad Sci 890:261–269PubMedCrossRefGoogle Scholar
  118. 118.
    Teng YD, Choi H, Onario RC et al (2004) Minocycline inhibits contusion-triggered mitochondrial cytochrome c release and mitigates functional deficits after spinal cord injury. Proc Natl Acad Sci USA 101(9):3071–3076PubMedCrossRefGoogle Scholar
  119. 119.
    Wu KL, Hsu C, Chan JY (2009) Nitric oxide and superoxide anion differentially activate poly(ADP-ribose) polymerase-1 and Bax to induce nuclear translocation of apoptosis-inducing factor and mitochondrial release of cytochrome c after spinal cord injury. J Neurotrauma 26(7):965–977PubMedCrossRefGoogle Scholar
  120. 120.
    Gensel JC, Tovar CA, Bresnahan JC, Beattie MS (2012) Topiramate treatment is neuroprotective and reduces oligodendrocyte loss after cervical spinal cord injury. PLoS ONE 7(3):e33519PubMedCrossRefGoogle Scholar
  121. 121.
    Kumru H, Kofler M (2012) Effect of spinal cord injury and of intrathecal baclofen on brainstem reflexes. Clin Neurophysiol 123(1):45–53PubMedCrossRefGoogle Scholar
  122. 122.
    Rong W, Wang J, Liu X et al (2012) 17beta-estradiol attenuates neural cell apoptosis through inhibition of JNK phosphorylation in SCI rats and excitotoxicity induced by glutamate in vitro. Int J Neurosci 122(7):381–387PubMedCrossRefGoogle Scholar
  123. 123.
    Garcia-Zozaya IA (2006) Adrenal insufficiency in acute spinal cord injury. J Spinal Cord Med 29(1):67–69PubMedGoogle Scholar
  124. 124.
    Samantaray S, Matzelle DD, Ray SK, Banik NL (2010) Physiological low dose of estrogen-protected neurons in experimental spinal cord injury. Ann N Y Acad Sci 1199:86–89PubMedCrossRefGoogle Scholar
  125. 125.
    Ji B, Li M, Wu WT, Yick LW et al (2006) LINGO-1 antagonist promotes functional recovery and axonal sprouting after spinal cord injury. Mol Cell Neurosci 33(3):311–320PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Abhay K. Varma
    • 1
  • Arabinda Das
    • 1
  • Gerald WallaceIV
    • 1
  • John Barry
    • 2
  • Alexey A. Vertegel
    • 2
  • Swapan K. Ray
    • 3
  • Naren L. Banik
    • 1
  1. 1.Department of NeurosciencesMedical University of South CarolinaCharlestonUSA
  2. 2.BioengineeringClemson UniversityClemsonUSA
  3. 3.Department of Pathology, Microbiology, and ImmunologyUniversity of South Carolina School of MedicineColumbiaUSA

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