Acute traumatic spinal cord injury

Pathophysiology and modern treatment concepts

  • Marko Jug Department of Traumatology, Division of Surgery, University Medical Centre Ljubljana, Ljubljana, Slovenia
Keywords: spinal cord, injury, pathophysiology, treatment, decompression


Traumatic spinal cord injury (tSCI) is a devastating event with huge impact on modern society. Despite recent advancements in different therapeutic strategies in preclinical models the transition of these approaches into the clinical setting remains elusive. However, recent studies showed that urgent spinal cord decompression and adequate spinal cord perfusion have a positive effect on neurologic recovery. Additional treatment strategies that try to address the complexity of tSCI are under clinical investigation and follow a superior understanding of pathophysiologic processes involved in tSCI. Therefore, in this review we present a comprehensive understanding of pathophysiologic processes involved in tSCI with emerging and evolving concepts of modern treatment.


Download data is not yet available.


Branco F, Cardenas DD, Svircev JN. Spinal cord injury: a comprehensive review. Phys Med Rehabil Clin N Am. 2007 Nov;18(4):651–79. PMID:17967359

Post MW, van Leeuwen CM. Psychosocial issues in spinal cord injury: a review. Spinal Cord. 2012 May;50(5):382–9. PMID:22270190

Singh A, Tetreault L, Kalsi-Ryan S, Nouri A, Fehlings MG. Global prevalence and incidence of traumatic spinal cord injury. Clin Epidemiol. 2014 Sep;6:309–31. PMID:25278785

Sekhon LH, Fehlings MG. Epidemiology, demographics, and pathophysiology of acute spinal cord injury. Spine. 2001 Dec;26(24 Suppl):S2–12. PMID:11805601

Pirouzmand F. Epidemiological trends of spine and spinal cord injuries in the largest Canadian adult trauma center from 1986 to 2006. J Neurosurg Spine. 2010 Feb;12(2):131–40. PMID:20121346

Chamberlain JD, Deriaz O, Hund-Georgiadis M, Meier S, Scheel-Sailer A, Schubert M, et al. Epidemiology and contemporary risk profile of traumatic spinal cord injury in Switzerland. Inj Epidemiol. 2015;2(1):28. PMID:26550554

Jabbour P, Fehlings M, Vaccaro AR, Harrop JS. Traumatic spine injuries in the geriatric population. Neurosurg Focus. 2008;25(5):E16. PMID:19067564

McCaughey EJ, Purcell M, McLean AN, Fraser MH, Bewick A, Borotkanics RJ, et al. Changing demographics of spinal cord injury over a 20-year period: a longitudinal population-based study in Scotland. Spinal Cord. 2016 Apr;54(4):270–6. PMID:26458974

Ahuja CS, Wilson JR, Nori S, Kotter MR, Druschel C, Curt A, et al. Traumatic spinal cord injury. Nat Rev Dis Primers. 2017 Apr;3(1):17018. PMID:28447605

Fehlings MG, Sekhon L. Cellular, ionic and biomolecular mechanisms of the injury process. In: Benzel E, Tator CH, editors. Contemporary Management of Spinal Cord Injury: From Impact to Rehabilitation. Chicago (IL): American Association of Neurological Surgeons; 2000. pp. 33–50.

Tator CH. Pathophysiology and pathology of spinal cord injury. In: Wilkins RH, Rengachary SS, editors. Neurosurgery. 2nd ed. New York (NY): McGraw- Hill; 1996. pp. 2847–59.

Oyinbo CA. Secondary injury mechanisms in traumatic spinal cord injury: a nugget of this multiply cascade. Acta Neurobiol Exp (Wars). 2011;71(2):281–99. PMID:21731081

Sullivan PG, Krishnamurthy S, Patel SP, Pandya JD, Rabchevsky AG. Temporal characterization of mitochondrial bioenergetics after spinal cord injury. J Neurotrauma. 2007 Jun;24(6):991–9. PMID:17600515

Xu GY, Hughes MG, Zhang L, Cain L, McAdoo DJ. Administration of glutamate into the spinal cord at extracellular concentrations reached post-injury causes functional impairments. Neurosci Lett. 2005b Aug;384(3):271–6. PMID:15925447

Fehlings MG, Nguyen DH. Immunoglobulin G: a potential treatment to attenuate neuroinflammation following spinal cord injury. J Clin Immunol. 2010 May;30(S1 Suppl 1):S109–12. PMID:20437085

Resnick DK. Updated guidelines for the management of acute cervical spine and spinal cord injury. Neurosurgery. 2013 Mar;72 Suppl 2:1. PMID:23417171

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 Aug;87(2):239–46. PMID:9254087

Ahuja CS, Wilson JR, Nori S, Kotter MR, Druschel C, Curt A, et al. Traumatic spinal cord injury. Nat Rev Dis Primers. 2017 Apr;3(1):17018. PMID:28447605

Kwon BK, Okon E, Hillyer J, Mann C, Baptiste D, Weaver LC, et al. A systematic review of non-invasive pharmacologic neuroprotective treatments for acute spinal cord injury. J Neurotrauma. 2011 Aug;28(8):1545–88. PMID:20146558

Popovich PG, Guan Z, Wei P, Huitinga I, van Rooijen N, Stokes BT. Depletion of hematogenous macrophages promotes partial hindlimb recovery and neuroanatomical repair after experimental spinal cord injury. Exp Neurol. 1999 Aug;158(2):351–65. PMID:10415142

Wells JE, Hurlbert RJ, Fehlings MG, Yong VW. Neuroprotection by minocycline facilitates significant recovery from spinal cord injury in mice. Brain. 2003 Jul;126(Pt 7):1628–37. PMID:12805103

Gris D, Marsh DR, Oatway MA, Chen Y, Hamilton EF, Dekaban GA, et al. Transient blockade of the CD11d/CD18 integrin reduces secondary damage after spinal cord injury, improving sensory, autonomic, and motor function. J Neurosci. 2004 Apr;24(16):4043–51. PMID:15102919

Schwartz M, Yoles E. Immune-based therapy for spinal cord repair: autologous macrophages and beyond. J Neurotrauma. 2006 Mar-Apr;23(3-4):360–70. PMID:16629622

Hirbec H, Gaviria M, Vignon J. Gacyclidine: a new neuroprotective agent acting at the N-methyl-D-aspartate receptor. CNS Drug Rev. 2001;7(2):172–98. PMID:11474423

Hall ED, Braughler JM. Glucocorticoid mechanisms in acute spinal cord injury: a review and therapeutic rationale. Surg Neurol. 1982 Nov;18(5):320–7. PMID:7179094

Golding JD, Rigley MacDonald ST, Juurlink BH, Rosser BW. The effect of glutamine on locomotor performance and skeletal muscle myosins following spinal cord injury in rats. J Appl Physiol (1985). 2006 Oct;101(4):1045–52. PMID:16778003

Faden AI, Jacobs TP, Mougey E, Holaday JW. Endorphins in experimental spinal injury: therapeutic effect of naloxone. Ann Neurol. 1981 Oct;10(4):326–32. PMID:6274252

Luo J, Borgens R, Shi R. Polyethylene glycol immediately repairs neuronal membranes and inhibits free radical production after acute spinal cord injury. J Neurochem. 2002 Oct;83(2):471–80. PMID:12423257

Baptiste DC, Fehlings MG. Pharmacological approaches to repair the injured spinal cord. J Neurotrauma. 2006 Mar-Apr;23(3-4):318–34. PMID:16629619

Bracken MB, Holford TR. Effects of timing of methylprednisolone or naloxone administration on recovery of segmental and long-tract neurological function in NASCIS 2. J Neurosurg. 1993 Oct;79(4):500–7. PMID:8410217

Bracken MB, Shepard MJ, Collins WF, Holford TR, Young W, Baskin DS, et al. 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. N Engl J Med. 1990 May;322(20):1405–11. PMID:2278545

Bracken MB, Holford TR. Effects of timing of methylprednisolone or naloxone administration on recovery of segmental and long-tract neurological function in NASCIS 2. J Neurosurg. 1993 Oct;79(4):500–7. PMID:8410217

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.How might we step forward? Pharmacol Ther. 2011;132:15–29.

Evaniew N, Noonan VK, Fallah N, Kwon BK, Rivers CS, Ahn H, et al.; RHSCIR Network. Methylprednisolone for the Treatment of Patients with Acute Spinal Cord Injuries: A Propensity Score-Matched Cohort Study from a Canadian Multi-Center Spinal Cord Injury Registry. J Neurotrauma. 2015 Nov;32(21):1674–83. PMID:26065706

Fehlings MG, Wilson JR, Cho N. Methylprednisolone for the treatment of acute spinal cord injury: counterpoint. Neurosurgery. 2014 Aug;61 Suppl 1:36–42. PMID:25032529

Druschel C, Schaser KD, Schwab JM. Current practice of methylprednisolone administration for acute spinal cord injury in Germany: a national survey. Spine. 2013 May;38(11):E669–77. PMID:23446768

Nagoshi N, Nakashima H, Fehlings MG. Riluzole as a neuroprotective drug for spinal cord injury: from bench to bedside. Molecules. 2015 Apr;20(5):7775–89. PMID:25939067

Popovich PG, Lemeshow S, Gensel JC, Tovar CA. Independent evaluation of the effects of glibenclamide on reducing progressive hemorrhagic necrosis after cervical spinal cord injury. Exp Neurol. 2012 Feb;233(2):615–22. PMID:21145891

Simard JM, Tsymbalyuk O, Keledjian K, Ivanov A, Ivanova S, Gerzanich V. Comparative effects of glibenclamide and riluzole in a rat model of severe cervical spinal cord injury. Exp Neurol. 2012 Jan;233(1):566–74. PMID:22177998

Hosier H, Peterson D, Tsymbalyuk O, Keledjian K, Smith BR, Ivanova S, et al. A Direct Comparison of Three Clinically Relevant Treatments in a Rat Model of Cervical Spinal Cord Injury. J Neurotrauma. 2015 Nov;32(21):1633–44. PMID:26192071

Kurland DB, Tosun C, Pampori A, Karimy JK, Caffes NM, Gerzanich V, et al. Glibenclamide for the treatment of acute CNS injury. Pharmaceuticals (Basel). 2013 Oct;6(10):1287–303. PMID:24275850

Garbossa D, Boido M, Fontanella M, Fronda C, Ducati A, Vercelli A. Recent therapeutic strategies for spinal cord injury treatment: possible role of stem cells. Neurosurg Rev. 2012 Jul;35(3):293–311. PMID:22539011

Sabapathy V, Tharion G, Kumar S. Cell Therapy Augments Functional Recovery Subsequent to Spinal Cord Injury under Experimental Conditions. Stem Cells Int. 2015;2015:132-72. PMID:26240569

Tso D, McKinnon RD. Cell replacement therapy for central nervous system diseases. Neural Regen R Pearse DD, Bunge B. Designing cell- and gene-based regeneration strategies to repair the injured spinal cord. J Neurotraum 2006; 23: 438– 2015; 10: 1356–8.

Pearse DD, Bunge MB. Designing cell- and gene-based regeneration strategies to repair the injured spinal cord. J Neurotrauma. 2006 Mar-Apr;23(3-4):438–52. PMID:16629628

Thuret S, Moon LD, Gage FH. Therapeutic interventions after spinal cord injury. Nat Rev Neurosci. 2006 Aug;7(8):628–43. PMID:16858391

Li Y, Decherchi P, Raisman G. Transplantation of olfactory ensheathing cells into spinal cord lesions restores breathing and climbing. J Neurosci. 2003 Feb;23(3):727–31. PMID:12574399

Papastefanaki F, Chen J, Lavdas AA, Thomaidou D, Schachner M, Matsas R. Grafts of Schwann cells engineered to express PSA-NCAM promote functional recovery after spinal cord injury. Brain. 2007 Aug;130(Pt 8):2159–74. PMID:17626035

Dalamagkas K, Tsintou M, Seifalian A, Seifalian AM. Translational Regenerative Therapies for Chronic Spinal Cord Injury. Int J Mol Sci. 2018 Jun;19(6):E1776. PMID:29914060

Ayala-Cuellar AP, Kang JH, Jeung EB, Choi KC. Roles of Mesenchymal Stem Cells in Tissue Regeneration and Immunomodulation. Biomol Ther (Seoul). 2019 Jan;27(1):25–33. PMID:29902862

Saito F, Nakatani T, Iwase M, Maeda Y, Murao Y, Suzuki Y, et al. Administration of cultured autologous bone marrow stromal cells into cerebrospinal fluid in spinal injury patients: a pilot study. Restor Neurol Neurosci. 2012;30(2):127–36. PMID:22232031

Mendonça MV, Larocca TF, de Freitas Souza BS, Villarreal CF, Silva LF, Matos AC, et al. Safety and neurological assessments after autologous transplantation of bone marrow mesenchymal stem cells in subjects with chronic spinal cord injury. Stem Cell Res Ther. 2014 Nov;5(6):126. PMID:25406723

Oraee-Yazdani S, Hafizi M, Atashi A, Ashrafi F, Seddighi AS, Hashemi SM, et al. Co-transplantation of autologous bone marrow mesenchymal stem cells and Schwann cells through cerebral spinal fluid for the treatment of patients with chronic spinal cord injury: safety and possible outcome. Spinal Cord. 2016 Feb;54(2):102–9. PMID:26526896

Karamouzian S, Nematollahi-Mahani SN, Nakhaee N, Eskandary H. Clinical safety and primary efficacy of bone marrow mesenchymal cell transplantation in subacute spinal cord injured patients. Clin Neurol Neurosurg. 2012 Sep;114(7):935–9. PMID:22464434

Gao F, Chiu SM, Motan DA, Zhang Z, Chen L, Ji HL, Tse HF, Fu QL, Lian Q. Mesenchymal stem cells and immunomodulation: current status and future prospects. Review. PubMed PMID: 26794657; PubMed Central PMCID: PMC4816164.

Ma S, Xie N, Li W, Yuan B, Shi Y, Wang Y. Immunobiology of mesenchymal stem cells. Epub 2013 Nov 1. Review. PubMed PMID: 24185619; PubMed Central PMCID: PMC3890955.

Vaquero J, Zurita M, Rico MA, Bonilla C, Aguayo C, Fernández C, et al.; Neurological Cell Therapy Group. Repeated subarachnoid administrations of autologous mesenchymal stromal cells supported in autologous plasma improve quality of life in patients suffering incomplete spinal cord injury. Cytotherapy. 2017 Mar;19(3):349–59. PMID:28089079

Spinal Cord Outcomes Partnership Endeavor. (SCOPE, Current SCI Clinical Trials of Rehabilitation and Technological Interventions to Improve Functional Outcomes. Revised September 6, 2018 Listing 82 Trials.

Vaquero J, Zurita M. Cell transplantation in paraplegic patients: the importance of properly assessing the spinal cord morphology. Clin Transplant. 2013 Nov-Dec;27(6):968–71. PMID:24147851

Polderman KH. Mechanisms of action, physiological effects, and complications of hypothermia. Crit Care Med. 2009 Jul;37(7 Suppl):S186–202. PMID:19535947

Dietrich WD, Levi AD, Wang M, Green BA. Hypothermic treatment for acute spinal cord injury. Neurotherapeutics. 2011 Apr;8(2):229–39. PMID:21416406

Lo TP Jr, Cho KS, Garg MS, Lynch MP, Marcillo AE, Koivisto DL, et al. Systemic hypothermia improves histological and functional outcome after cervical spinal cord contusion in rats. J Comp Neurol. 2009 Jun;514(5):433–48. PMID:19350644

Hosier H, Peterson D, Tsymbalyuk O, Keledjian K, Smith BR, Ivanova S, et al. A Direct Comparison of Three Clinically Relevant Treatments in a Rat Model of Cervical Spinal Cord Injury. J Neurotrauma. 2015 Nov;32(21):1633–44. PMID:26192071

Levi AD, Casella G, Green BA, Dietrich WD, Vanni S, Jagid J, et al. Clinical outcomes using modest intravascular hypothermia after acute cervical spinal cord injury. Neurosurgery. 2010 Apr;66(4):670–7. PMID:20190669

Dididze M, Green BA, Dietrich WD, Vanni S, Wang MY, Levi AD. Systemic hypothermia in acute cervical spinal cord injury: a case-controlled study. Spinal Cord. 2013 May;51(5):395–400. PMID:23247015

Batchelor PE, Kerr NF, Gatt AM, Aleksoska E, Cox SF, Ghasem-Zadeh A, Wills TE, Howells DW. Hypothermia prior to decompression: buying time for treatment of acute spinal cord injury. J Neurotrauma. 2010 Aug;27(8):1357-68. PMID:20504158

Antonic A, Dottori M, Leung J, Sidon K, Batchelor PE, Wilson W, et al. Hypothermia protects human neurons. Int J Stroke. 2014 Jul;9(5):544–52. PMID:24393199

American Spinal Injury Association. Chicago: American Spinal Injury Association; 2000.

Gerecht R. The lethal triad. Hypothermia, acidosis & coagulopathy create a deadly cycle for trauma patients. JEMS. 2014 Apr;39(4):56–60. PMID:24779101

Varon J, Acosta P. Therapeutic hypothermia: past, present, and future. Chest. 2008 May;133(5):1267–74. PMID:18460529

Hansebout RR, Hansebout CR. Local cooling for traumatic spinal cord injury: outcomes in 20 patients and review of the literature. J Neurosurg Spine. 2014 May;20(5):550–61. PMID:24628130

Alkabie S, Boileau AJ. The Role of Therapeutic Hypothermia After Traumatic Spinal Cord Injury—A Systematic Review. World Neurosurg. 2016 Feb;86:432–49. PMID:26433095

Huang WL, King VR, Curran OE, Dyall SC, Ward RE, Lal N, et al. A combination of intravenous and dietary docosahexaenoic acid significantly improves outcome after spinal cord injury. Brain. 2007 Nov;130(Pt 11):3004–19. PMID:17901087

Lim SN, Huang W, Hall JC, Michael-Titus AT, Priestley JV. Improved outcome after spinal cord compression injury in mice treated with docosahexaenoic acid. Exp Neurol. 2013 Jan;239:13–27. PMID:23026410

Streijger F, Plunet WT, Lee JH, Liu J, Lam CK, Park S, et al. Ketogenic diet improves forelimb motor function after spinal cord injury in rodents. PLoS One. 2013 Nov;8(11):e78765. PMID:24223849

Jeong MA, Plunet W, Streijger F, Lee JH, Plemel JR, Park S, et al. Intermittent fasting improves functional recovery after rat thoracic contusion spinal cord injury. J Neurotrauma. 2011 Mar;28(3):479–92. PMID:21219083

Rabchevsky AG, Patel SP, Springer JE. Pharmacological interventions for spinal cord injury: where do we stand? How might we step forward? Pharmacol Ther. 2011 Oct;132(1):15–29. PMID:21605594

Carlson GD, Minato Y, Okada A, Gorden CD, Warden KE, Barbeau JM, et al. Early time-dependent decompression for spinal cord injury: vascular mechanisms of recovery. J Neurotrauma. 1997a Dec;14(12):951–62. PMID:9475376

Carlson GD, Warden KE, Barbeau JM, Bahniuk E, Kutina-Nelson KL, Biro CL, et al. Viscoelastic relaxation and regional blood flow response to spinal cord compression and decompression. Spine. 1997b Jun;22(12):1285–91. PMID:9201829

Dimar JR 2nd, Glassman SD, Raque GH, Zhang YP, Shields CB. The influence of spinal canal narrowing and timing of decompression on neurologic recovery after spinal cord contusion in a rat model. Spine. 1999 Aug;24(16):1623–33. PMID:10472095

Furlan JC, Noonan V, Cadotte DW, Fehlings MG. Timing of decompressive surgery of spinal cord after traumatic spinal cord injury: an evidence-based examination of pre-clinical and clinical studies. J Neurotrauma. 2011 Aug;28(8):1371–99. PMID:20001726

Pointillart V, Petitjean ME, Wiart L, Vital JM, Lassié P, Thicoipé M, et al. Pharmacological therapy of spinal cord injury during the acute phase. Spinal Cord. 2000 Feb;38(2):71–6. PMID:10762178

van Middendorp JJ, Hosman AJ, Doi SA. The effects of the timing of spinal surgery after traumatic spinal cord injury: a systematic review and meta-analysis. J Neurotrauma. 2013 Nov;30(21):1781–94. PMID:23815524

Fehlings MG, Vaccaro A, Wilson JR, Singh A, W Cadotte D, Harrop JS, et al. Early versus delayed decompression for traumatic cervical spinal cord injury: results of the Surgical Timing in Acute Spinal Cord Injury Study (STASCIS). PLoS One. 2012;7(2):e32037. PMID:22384132

Wilson JR, Singh A, Craven C, Verrier MC, Drew B, Ahn H, et al. Early versus late surgery for traumatic spinal cord injury: the results of a prospective Canadian cohort study. Spinal Cord. 2012 Nov;50(11):840–3. PMID:22565550

Wilson JR, Lindsay BSc LT, Aarabi B, Anderson PA, Arnold PM, Brodke DS, et al. 181 guidelines for the management of patients with spinal cord injury: The optimal timing of decompression. Neurosurgery. 2016 Aug;63 Suppl 1:172.

Jug M, Kejžar N, Vesel M, Al Mawed S, Dobravec M, Herman S, et al. Neurological Recovery after Traumatic Cervical Spinal Cord Injury Is Superior if Surgical Decompression and Instrumented Fusion Are Performed within 8 Hours versus 8 to 24 Hours after Injury: A Single Center Experience. J Neurotrauma. 2015 Sep;32(18):1385–92. PMID:25658291

Grassner L, Wutte C, Klein B, Mach O, Riesner S, Panzer S, et al. Early Decompression (< 8 h) after Traumatic Cervical Spinal Cord Injury Improves Functional Outcome as Assessed by Spinal Cord Independence Measure after One Year. J Neurotrauma. 2016 Sep;33(18):1658–66. PMID:27050499

Saadoun S, Chen S, Papadopoulos MC. Intraspinal pressure and spinal cord perfusion pressure predict neurological outcome after traumatic spinal cord injury. J Neurol Neurosurg Psychiatry. 2017 May;88(5):452–3. PMID:27864426

Phang I, Zoumprouli A, Saadoun S, Papadopoulos MC. Safety profile and probe placement accuracy of intraspinal pressure monitoring for traumatic spinal cord injury: Injured Spinal Cord Pressure Evaluation study. J Neurosurg Spine. 2016 Sep;25(3):398–405. PMID:27129044

Phang I, Werndle MC, Saadoun S, Varsos G, Czosnyka M, Zoumprouli A, et al. Expansion duroplasty improves intraspinal pressure, spinal cord perfusion pressure, and vascular pressure reactivity index in patients with traumatic spinal cord injury: injured spinal cord pressure evaluation study. J Neurotrauma. 2015 Jun;32(12):865–74. PMID:25705999

How to Cite
Jug M. Acute traumatic spinal cord injury. TEST ZdravVestn [Internet]. 28Oct.2019 [cited 10Apr.2020];88(9-10):444-7. Available from: