Abstract
Spinal cord injury (SCI) is a life-shattering neurological condition that affects between 250,000 and 500,000 individuals each year with an estimated two to three million people worldwide living with an SCI-related disability. The incidence in the USA and Canada is more than that in other countries with motor vehicle accidents being the most common cause, while violence being most common in the developing nations. Its incidence is two- to fivefold higher in males, with a peak in younger adults. Apart from the economic burden associated with medical care costs, SCI predominantly affects a younger adult population. Therefore, the psychological impact of adaptation of an average healthy individual as a paraplegic or quadriplegic with bladder, bowel, or sexual dysfunction in their early life can be devastating. People with SCI are two to five times more likely to die prematurely, with worse survival rates in low- and middle-income countries. This devastating disorder has a complex and multifaceted mechanism. Recently, a lot of research has been published on the restoration of locomotor activity and the therapeutic strategies. Therefore, it is imperative for the treating physicians to understand the complex underlying pathophysiological mechanisms of SCI.
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References
WHO (2017) Spinal cord injury. Available from: http://www.who.int/mediacentre/factsheets/fs384/en/
Wyndaele M, Wyndaele JJ (2006) Incidence, prevalence and epidemiology of spinal cord injury: what learns a worldwide literature survey? Spinal Cord 44(9):523–529
Selassie A, Cao Y, Saunders LL (2015) Epidemiology of traumatic spinal cord injury among persons older than 21 years: a population-based study in South Carolina, 1998-2012. Top Spinal Cord Inj Rehabil 21(4):333–344
National Spinal Cord Injury Statistical Center (2015) Facts and figures at a glance. University of Alabama at Birmingham. Available at: http://www.msktc.org/lib/docs/Data_Sheets_/MSKTC_SCIMS_Fact_Fig_2015.pdf, Birmingham
Jazayeri SB, Beygi S, Shokraneh F, Hagen EM, Rahimi-Movaghar V (2015) Incidence of traumatic spinal cord injury worldwide: a systematic review. Eur Spine J 24(5):905–918
Singh A et al (2014) Global prevalence and incidence of traumatic spinal cord injury. Clin Epidemiol 6:309–331
Rahimi-Movaghar V, Sayyah MK, Akbari H, Khorramirouz R, Rasouli MR, Moradi-Lakeh M, Shokraneh F, Vaccaro AR (2013) Epidemiology of traumatic spinal cord injury in developing countries: a systematic review. Neuroepidemiology 41(2):65–85
Klebine P (2015) Understanding spinal cord injury: part 1—the body before and after injury in collaboration with the model systems knowledge translation center. The National Spinal Cord Injury Statistical Center
Mortazavi M, Gore PA, Chang S, Tubbs RS, Theodore N (2011) Pediatric cervical spine injuries: a comprehensive review. Childs Nerv Syst 27(5):705–717
Mortazavi MM, Dogan S, Civelek E, Tubbs RS, Theodore N, Rekate HL, Sonntag VKH (2011) Pediatric multilevel spine injuries: an institutional experience. Childs Nerv Syst 27(7):1095–1100
Krueger H et al (2013) The economic burden of traumatic spinal cord injury in Canada. Chronic Dis Inj Can 33(3):113–122
Collie A, Keating C, Pezzullo L, Gabbe B, Cooper J, Brown D, Olver J, McCartin F, Trethewey P (2010) Brain and spinal cord injury in Australia—economic cost and burden of disease. Inj Prev 16(Suppl 1):A25–A26
Sekhon LH, Fehlings MG (2001) Epidemiology, demographics, and pathophysiology of acute spinal cord injury. Spine (Phila Pa 1976) 26(24 Suppl):S2–S12
Hohmann GW (1975) Psychological aspects of treatment and rehabilitation of the spinal cord injured person. Clin Orthop Relat Res 112:81–88
Orbaan IJ (1986) Psychological adjustment problems in people with traumatic spinal cord lesions. Acta Neurochir 79(1):58–61
Nas K et al (2015) Rehabilitation of spinal cord injuries. World J Orthop 6(1):8–16
Mortazavi MM, Mariwalla NR, Horn EM, Tubbs RS, Theodore N (2011) Absence of MRI soft tissue abnormalities in severe spinal cord injury in children: case-based update. Childs Nerv Syst 27(9):1369–1373
Yang XX, Huang ZQ, Li ZH, Ren DF, Tang JG (2017) Risk factors and the surgery affection of respiratory complication and its mortality after acute traumatic cervical spinal cord injury. Medicine (Baltimore) 96(36):e7887
Majdan M, Plancikova D, Nemcovska E, Krajcovicova L, Brazinova A, Rusnak M (2017) Mortality due to traumatic spinal cord injuries in Europe: a cross-sectional and pooled analysis of population-wide data from 22 countries. Scand J Trauma Resusc Emerg Med 25(1):64
Biering-Sorensen F et al (2017) International Spinal Cord Injury Core Data Set (version 2.0)—including standardization of reporting. Spinal Cord 55(8):759–764
Sobani ZA, Quadri SA, Enam SA (2010) Stem cells for spinal cord regeneration: current status. Surg Neurol Int 1:93
Jackson A, Zimmermann JB (2012) Neural interfaces for the brain and spinal cord—restoring motor function. Nat Rev Neurol 8(12):690–699
Chari A, Hentall I, Papadopoulos M, Pereira E (2017) Surgical neurostimulation for spinal cord injury. Brain Sci 7(2)
Fehlings MG, Wilson JR, Frankowski RF, Toups EG, Aarabi B, Harrop JS, Shaffrey CI, Harkema SJ, Guest JD, Tator CH, Burau KD, Johnson MW, Grossman RG (2012) Riluzole for the treatment of acute traumatic spinal cord injury: rationale for and design of the NACTN phase I clinical trial. J Neurosurg Spine 17(1 Suppl):151–156
Casha S, Zygun D, McGowan MD, Bains I, Yong VW, John Hurlbert R (2012) Results of a phase II placebo-controlled randomized trial of minocycline in acute spinal cord injury. Brain 135(Pt 4):1224–1236
Hayta E, Elden H (2017) Acute spinal cord injury: a review of pathophysiology and potential of non-steroidal anti-inflammatory drugs for pharmacological intervention. J Chem Neuroanat 87:25–31
Phillips AA, Krassioukov AV (2015) Contemporary cardiovascular concerns after spinal cord injury: mechanisms, maladaptations, and management. J Neurotrauma 32(24):1927–1942
Meister R et al (2014) Neurogenic shock. Rev Med Suisse 10(438):1506–1510
Marx JA, Rosen P (2014) Rosen’s emergency medicine: concepts and clinical practice, 8th edn. Elsevier/Saunders, Philadelphia
American Spinal Injury Association (ASIA) (1998) Abstracts. J Spinal Cord Med 21(2):151–194
Roberts TT, Leonard GR, Cepela DJ (2017) Classifications in brief: American Spinal Injury Association (ASIA) Impairment Scale. Clin Orthop Relat Res 475(5):1499–1504
Anderson DK, Means ED, Waters TR, Green ES (1982) Microvascular perfusion and metabolism in injured spinal cord after methylprednisolone treatment. J Neurosurg 56(1):106–113
Tubbs RS, Blouir MC, Romeo AK, Mortazavi MM, Cohen-Gadol AA (2011) Spinal cord ischemia and atherosclerosis: a review of the literature. Br J Neurosurg 25(6):666–670
Kobayashi T (1968) Experimental study on pathological phases of whiplash injury. Nihon Seikeigeka Gakkai Zasshi 42(1):1–12
Allen A (1911) Surgery of experimental lesion of spinal cord equivalent to crush injury of fracture dislocation of spinal column: a preliminary report. J Am Med Assoc LVII(11):878–880
Mortazavi MM, Verma K, Deep A, Esfahani FB, Pritchard PR, Tubbs RS, Theodore N (2011) Chemical priming for spinal cord injury: a review of the literature. Part I—factors involved. Childs Nerv Syst 27(8):1297–1306
Ray SK, Dixon CE, Banik NL (2002) Molecular mechanisms in the pathogenesis of traumatic brain injury. Histol Histopathol 17(4):1137–1152
Rossignol S, Schwab M, Schwartz M, Fehlings MG (2007) Spinal cord injury: time to move? J Neurosci 27(44):11782–11792
Oyinbo CA (2011) Secondary injury mechanisms in traumatic spinal cord injury: a nugget of this multiply cascade. Acta Neurobiol Exp (Wars) 71(2):281–299
Borgens RB, Liu-Snyder P (2012) Understanding secondary injury. Q Rev Biol 87(2):89–127
Bastien D, Lacroix S (2014) Cytokine pathways regulating glial and leukocyte function after spinal cord and peripheral nerve injury. Exp Neurol 258:62–77
Beattie MS, Farooqui AA, Bresnahan JC (2000) Review of current evidence for apoptosis after spinal cord injury. J Neurotrauma 17(10):915–925
Tator CH et al (1984) Management of acute spinal cord injuries. Can J Surg 27(3):289–293 296
Dumont RJ, Verma S, Okonkwo DO, Hurlbert RJ, Boulos PT, Ellegala DB, Dumont AS (2001) Acute spinal cord injury, part II: contemporary pharmacotherapy. Clin Neuropharmacol 24(5):265–279
Benzel EC, Larson SJ (1986) Functional recovery after decompressive operation for thoracic and lumbar spine fractures. Neurosurgery 19(5):772–778
Suwanwela C, Alexander E Jr, Davis CH Jr (1962) Prognosis in spinal cord injury, with special reference to patients with motor paralysis and sensory preservation. J Neurosurg 19:220–227
Kojima Y et al (1979) Evoked spinal potentials as a monitor of spinal cord viability. Spine (Phila Pa 1976) 4(6):471–477
Saul TG, Carol M, Ducker TB (1982) Immediate mini-myelography in acute cervical cord injuries. Am Surg 48(9):463–468
Oiwa T (1983) Experimental study on the post-laminectomy deterioration in cervical spondylotic myelopathy—influences of the meningeal treatment and persistent spinal cord block. Nihon Seikeigeka Gakkai Zasshi 57(6):577–592
Elia C, Hariri OR, Duong J, Dong F, Sweiss R, Miulli D (2018) Use of a pediatric craniotome drill for cervical and thoracic spine decompression: safety and efficacy. World Neurosurg 113:e486–e489
Tator CH (1995) Update on the pathophysiology and pathology of acute spinal cord injury. Brain Pathol 5(4):407–413
Hariri OR (2018) Posterior-only stabilization for traumatic thoracolumbar burst fractures. Cureus 10(3):e2296
Young W (1993) Secondary injury mechanisms in acute spinal cord injury. J Emerg Med 11(Suppl 1):13–22
Pang D, Wilberger JE Jr (1982) Spinal cord injury without radiographic abnormalities in children. J Neurosurg 57(1):114–129
Tator CH, Fehlings MG (1991) Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms. J Neurosurg 75(1):15–26
Wolman L (1965) The disturbance of circulation in traumatic paraplegia in acute and late stages: a pathological study. Paraplegia 2:213–226
Mortazavi MM, Verma K, Tubbs RS, Theodore N (2011) Cellular and paracellular transplants for spinal cord injury: a review of the literature. Childs Nerv Syst 27(2):237–243
Mortazavi MM, Verma K, Deep A, Esfahani FB, Pritchard PR, Tubbs RS, Theodore N (2011) Chemical priming for spinal cord injury: a review of the literature part II—potential therapeutics. Childs Nerv Syst 27(8):1307–1316
Popa C et al (2010) Vascular dysfunctions following spinal cord injury. J Med Life 3(3):275–285
Losey P, Anthony DC (2014) Impact of vasculature damage on the outcome of spinal cord injury: a novel collagenase-induced model may give new insights into the mechanisms involved. Neural Regen Res 9(20):1783–1786
Blight AR, Young W (1989) Central axons in injured cat spinal cord recover electrophysiological function following remyelination by Schwann cells. J Neurol Sci 91(1–2):15–34
Mortazavi MM, Verma K, Harmon OA, Griessenauer CJ, Adeeb N, Theodore N, Tubbs RS (2015) The microanatomy of spinal cord injury: a review. Clin Anat 28(1):27–36
Guha A, Tator CH, Rochon J (1989) Spinal cord blood flow and systemic blood pressure after experimental spinal cord injury in rats. Stroke 20(3):372–377
Minassian K et al. (2002) Effective spinal cord stimulation (SCS) for evoking stepping movement of paralyzed human lower limbs: study of posterior root muscle reflex responses. na
Vogel C, Rukwied R, Stockinger L, Schley M, Schmelz M, Schleinzer W, Konrad C (2017) Functional characterization of at-level hypersensitivity in patients with spinal cord injury. J Pain 18(1):66–78
Taylor SW, Laughlin RS, Kumar N, Goodman B, Klein CJ, Dyck PJ, Dyck PJB (2017) Clinical, physiological and pathological characterisation of the sensory predominant peripheral neuropathy in copper deficiency. J Neurol Neurosurg Psychiatry 88(10):839–845
Berger MJ, Kimpinski K, Currie KD, Nouraei H, Sadeghi M, Krassioukov AV (2017) Multi-domain assessment of autonomic function in spinal cord injury using a modified autonomic reflex screen. J Neurotrauma 34(18):2624–2633
Lee JS, Fang SY, Roan JN, Jou IM, Lam CF (2016) Spinal cord injury enhances arterial expression and reactivity of alpha1-adrenergic receptors-mechanistic investigation into autonomic dysreflexia. Spine J 16(1):65–71
Anthes DL, Theriault E, Tator CH (1996) Ultrastructural evidence for arteriolar vasospasm after spinal cord trauma. Neurosurgery 39(4):804–814
Tator CH, Koyanagi I (1997) Vascular mechanisms in the pathophysiology of human spinal cord injury. J Neurosurg 86(3):483–492
Holtz A, Nystrom B, Gerdin B (1990) Relation between spinal cord blood flow and functional recovery after blocking weight-induced spinal cord injury in rats. Neurosurgery 26(6):952–957
Ouyang H, Sun W, Fu Y, Li J, Cheng JX, Nauman E, Shi R (2010) Compression induces acute demyelination and potassium channel exposure in spinal cord. J Neurotrauma 27(6):1109–1120
Hendricks BK, Shi R (2014) Mechanisms of neuronal membrane sealing following mechanical trauma. Neurosci Bull 30(4):627–644
Arancibia-Carcamo IL, Attwell D (2014) The node of Ranvier in CNS pathology. Acta Neuropathol 128(2):161–175
Vacher H, Mohapatra DP, Trimmer JS (2008) Localization and targeting of voltage-dependent ion channels in mammalian central neurons. Physiol Rev 88(4):1407–1447
Lorincz A, Nusser Z (2010) Molecular identity of dendritic voltage-gated sodium channels. Science 328(5980):906–909
Sun W, Fu Y, Shi Y, Cheng JX, Cao P, Shi R (2012) Paranodal myelin damage after acute stretch in guinea pig spinal cord. J Neurotrauma 29(3):611–619
Fu Y, Sun W, Shi Y, Shi R, Cheng JX (2009) Glutamate excitotoxicity inflicts paranodal myelin splitting and retraction. PLoS One 4(8):e6705
Khalaj AJ, Hasselmann J, Augello C, Moore S, Tiwari-Woodruff SK (2016) Nudging oligodendrocyte intrinsic signaling to remyelinate and repair: estrogen receptor ligand effects. J Steroid Biochem Mol Biol 160:43–52
Faden AI et al (1989) The role of excitatory amino acids and NMDA receptors in traumatic brain injury. Science 244(4906):798–800
Katayama Y, Becker DP, Tamura T, Hovda DA (1990) Massive increases in extracellular potassium and the indiscriminate release of glutamate following concussive brain injury. J Neurosurg 73(6):889–900
Palmer AM, Marion DW, Botscheller ML, Bowen DM, DeKosky ST (1994) Increased transmitter amino acid concentration in human ventricular CSF after brain trauma. Neuroreport 6(1):153–156
Hayes RL, Jenkins LW, Lyeth BG (1992) Neurotransmitter-mediated mechanisms of traumatic brain injury: acetylcholine and excitatory amino acids. J Neurotrauma 9(Suppl 1):S173–S187
Olney JW (1969) Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate. Science 164(3880):719–721
Weber JT (2004) Calcium homeostasis following traumatic neuronal injury. Curr Neurovasc Res 1(2):151–171
Young W (1992) Role of calcium in central nervous system injuries. J Neurotrauma 9(Suppl 1):S9–S25
Stirling DP, Cummins K, Wayne Chen SR, Stys P (2014) Axoplasmic reticulum Ca(2+) release causes secondary degeneration of spinal axons. Ann Neurol 75(2):220–229
Young W (1985) The role of calcium in spinal cord injury. Cent Nerv Syst Trauma 2(2):109–114
Pelisch N, Gomes C, Nally JM, Petruska JC, Stirling DP (2017) Differential expression of ryanodine receptor isoforms after spinal cord injury. Neurosci Lett 660:51–56
Villegas R, Martinez NW, Lillo J, Pihan P, Hernandez D, Twiss JL, Court FA (2014) Calcium release from intra-axonal endoplasmic reticulum leads to axon degeneration through mitochondrial dysfunction. J Neurosci 34(21):7179–7189
Mortazavi MM, Harmon OA, Adeeb N, Deep A, Tubbs RS (2015) Treatment of spinal cord injury: a review of engineering using neural and mesenchymal stem cells. Clin Anat 28(1):37–44
Fatima G, Sharma VP, Das SK, Mahdi AA (2015) Oxidative stress and antioxidative parameters in patients with spinal cord injury: implications in the pathogenesis of disease. Spinal Cord 53(1):3–6
Liu XZ, Xu XM, Hu R, du C, Zhang SX, McDonald JW, Dong HX, Wu YJ, Fan GS, Jacquin MF, Hsu CY, Choi DW (1997) Neuronal and glial apoptosis after traumatic spinal cord injury. J Neurosci 17(14):5395–5406
Ma M (2013) Role of calpains in the injury-induced dysfunction and degeneration of the mammalian axon. Neurobiol Dis 60:61–79
Mustafa AG, Wang JA, Carrico KM, Hall ED (2011) Pharmacological inhibition of lipid peroxidation attenuates calpain-mediated cytoskeletal degradation after traumatic brain injury. J Neurochem 117(3):579–588
Kaplan AE (1977) Spinal cord influences on immune responses demonstrated following interruption of the spinal cord as a result of injury. Zh Vopr Neirokhir Im N N Burdenko 6:40–43
Allan SM, Rothwell NJ (2003) Inflammation in central nervous system injury. Philos Trans R Soc Lond Ser B Biol Sci 358(1438):1669–1677
Schwab JM, Zhang Y, Kopp MA, Brommer B, Popovich PG (2014) The paradox of chronic neuroinflammation, systemic immune suppression, autoimmunity after traumatic chronic spinal cord injury. Exp Neurol 258:121–129
Plemel JR, Wee Yong V, Stirling DP (2014) Immune modulatory therapies for spinal cord injury—past, present and future. Exp Neurol 258:91–104
Anthony DC, Couch Y (2014) The systemic response to CNS injury. Exp Neurol 258:105–111
Zhou X, He X, Ren Y (2014) Function of microglia and macrophages in secondary damage after spinal cord injury. Neural Regen Res 9(20):1787–1795
Herrmann JE, Imura T, Song B, Qi J, Ao Y, Nguyen TK, Korsak RA, Takeda K, Akira S, Sofroniew MV (2008) STAT3 is a critical regulator of astrogliosis and scar formation after spinal cord injury. J Neurosci 28(28):7231–7243
Moriarty LJ, Borgens RB (1999) The effect of an applied electric field on macrophage accumulation within the subacute spinal injury. Restor Neurol Neurosci 14(1):53–64
Ma M, Wei T, Boring L, Charo IF, Ransohoff RM, Jakeman LB (2002) Monocyte recruitment and myelin removal are delayed following spinal cord injury in mice with CCR2 chemokine receptor deletion. J Neurosci Res 68(6):691–702
Zhang H, Trivedi A, Lee JU, Lohela M, Lee SM, Fandel TM, Werb Z, Noble-Haeusslein LJ (2011) Matrix metalloproteinase-9 and stromal cell-derived factor-1 act synergistically to support migration of blood borne monocytes into the injured spinal cord. J Neurosci 31(44):15894–15903
Zu J, Wang Y, Xu G, Zhuang J, Gong H, Yan J (2014) Curcumin improves the recovery of motor function and reduces spinal cord edema in a rat acute spinal cord injury model by inhibiting the JAK/STAT signaling pathway. Acta Histochem 116(8):1331–1336
Li X, Chen W, Sheng J, Cao D, Wang W (2014) Interleukin-6 inhibits voltage-gated sodium channel activity of cultured rat spinal cord neurons. Acta Neuropsychiatr 26(3):170–177
Oropallo MA, Goenka R, Cancro MP (2014) Spinal cord injury impacts B cell production, homeostasis, and activation. Semin Immunol 26(5):421–427
Sofroniew MV, Vinters HV (2010) Astrocytes: biology and pathology. Acta Neuropathol 119(1):7–35
Wanner IB, Anderson MA, Song B, Levine J, Fernandez A, Gray-Thompson Z, Ao Y, Sofroniew MV (2013) Glial scar borders are formed by newly proliferated, elongated astrocytes that interact to corral inflammatory and fibrotic cells via STAT3-dependent mechanisms after spinal cord injury. J Neurosci 33(31):12870–12886
Kawaja MD, Gage FH (1991) Reactive astrocytes are substrates for the growth of adult CNS axons in the presence of elevated levels of nerve growth factor. Neuron 7(6):1019–1030
Burda JE, Sofroniew MV (2014) Reactive gliosis and the multicellular response to CNS damage and disease. Neuron 81(2):229–248
Bush TG, Puvanachandra N, Horner CH, Polito A, Ostenfeld T, Svendsen CN, Mucke L, Johnson MH, Sofroniew MV (1999) Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice. Neuron 23(2):297–308
Drogemuller K, Helmuth U, Brunn A, Sakowicz-Burkiewicz M, Gutmann DH, Mueller W, Deckert M, Schluter D (2008) Astrocyte gp130 expression is critical for the control of toxoplasma encephalitis. J Immunol 181(4):2683–2693
Faulkner JR et al (2004) Reactive astrocytes protect tissue and preserve function after spinal cord injury. J Neurosci 24(9):2143–2155
Silver J, Edwards MA, Levitt P (1993) Immunocytochemical demonstration of early appearing astroglial structures that form boundaries and pathways along axon tracts in the fetal brain. J Comp Neurol 328(3):415–436
Williams RR, Henao M, Pearse DD, Bunge MB (2015) Permissive Schwann cell graft/spinal cord interfaces for axon regeneration. Cell Transplant 24(1):115–131
Zukor K, Belin S, Wang C, Keelan N, Wang X, He Z (2013) Short hairpin RNA against PTEN enhances regenerative growth of corticospinal tract axons after spinal cord injury. J Neurosci 33(39):15350–15361
Casha S, Yu WR, Fehlings MG (2001) Oligodendroglial apoptosis occurs along degenerating axons and is associated with FAS and p75 expression following spinal cord injury in the rat. Neuroscience 103(1):203–218
Spejo AB, Oliveira AL (2015) Synaptic rearrangement following axonal injury: old and new players. Neuropharmacology 96(Pt A):113–123
Ohtake Y, Li S (2015) Molecular mechanisms of scar-sourced axon growth inhibitors. Brain Res 1619:22–35
Dickendesher TL, Baldwin KT, Mironova YA, Koriyama Y, Raiker SJ, Askew KL, Wood A, Geoffroy CG, Zheng B, Liepmann CD, Katagiri Y, Benowitz LI, Geller HM, Giger RJ (2012) NgR1 and NgR3 are receptors for chondroitin sulfate proteoglycans. Nat Neurosci 15(5):703–712
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):6570–6577
Fournier AE, Strittmatter SM (2001) Repulsive factors and axon regeneration in the CNS. Curr Opin Neurobiol 11(1):89–94
Fournier AE, Takizawa BT, Strittmatter SM (2003) Rho kinase inhibition enhances axonal regeneration in the injured CNS. J Neurosci 23(4):1416–1423
Madura T, Yamashita T, Kubo T, Fujitani M, Hosokawa K, Tohyama M (2004) Activation of Rho in the injured axons following spinal cord injury. EMBO Rep 5(4):412–417
Laurén J, Hu F, Chin J, Liao J, Airaksinen MS, Strittmatter SM (2007) Characterization of myelin ligand complexes with the neuronal Nogo-66 receptor family. J Biol Chem 282(8):5715–5725
Bareyre FM, Haudenschild B, Schwab ME (2002) Long-lasting sprouting and gene expression changes induced by the monoclonal antibody IN-1 in the adult spinal cord. J Neurosci 22(16):7097–7110
Bregman BS, Kunkel-Bagden E, Schnell L, Dai HN, Gao D, Schwab ME (1995) Recovery from spinal cord injury mediated by antibodies to neurite growth inhibitors. Nature 378(6556):498–501
Fehlings MG, Theodore N, Harrop J, Maurais G, Kuntz C, Shaffrey CI, Kwon BK, Chapman J, Yee A, Tighe A, McKerracher L (2011) A phase I/IIa clinical trial of a recombinant Rho protein antagonist in acute spinal cord injury. J Neurotrauma 28(5):787–796
Squair JW, Bélanger LM, Tsang A, Ritchie L, Mac-Thiong JM, Parent S, Christie S, Bailey C, Dhall S, Street J, Ailon T, Paquette S, Dea N, Fisher CG, Dvorak MF, West CR, Kwon BK (2017) Spinal cord perfusion pressure predicts neurologic recovery in acute spinal cord injury. Neurology 89(16):1660–1667
Satyarthee GD (2018) Reader response: spinal cord perfusion pressure predicts neurologic recovery in acute spinal cord injury. Neurology 90(19):904
Tykocki T, Poniatowski Ł, Czyż M, Koziara M, Wynne-Jones G (2017) Intraspinal pressure monitoring and extensive duroplasty in the acute phase of traumatic spinal cord injury: a systematic review. World Neurosurg 105:145–152
Donati ARC, Shokur S, Morya E, Campos DSF, Moioli RC, Gitti CM, Augusto PB, Tripodi S, Pires CG, Pereira GA, Brasil FL, Gallo S, Lin AA, Takigami AK, Aratanha MA, Joshi S, Bleuler H, Cheng G, Rudolph A, Nicolelis MAL (2016) Long-term training with a brain-machine interface-based gait protocol induces partial neurological recovery in paraplegic patients. Sci Rep 6:30383
Guru K, Mailis A, Ashby P, Vanderlinden G (1987) Postsynaptic potentials in motoneurons caused by spinal cord stimulation in humans. Electroencephalogr Clin Neurophysiol 66(3):275–280
Dimitrijevic MR, Gerasimenko Y, Pinter MM (1998) Evidence for a spinal central pattern generator in humans. Ann N Y Acad Sci 860(1):360–376
Harkema S, Gerasimenko Y, Hodes J, Burdick J, Angeli C, Chen Y, Ferreira C, Willhite A, Rejc E, Grossman RG, Edgerton VR (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(9781):1938–1947
Gerasimenko YP, Makarovskii A, Nikitin O (2002) Control of locomotor activity in humans and animals in the absence of supraspinal influences. Neurosci Behav Physiol 32(4):417–423
Jilge B, Minassian K, Rattay F, Pinter MM, Gerstenbrand F, Binder H, Dimitrijevic MR (2004) Initiating extension of the lower limbs in subjects with complete spinal cord injury by epidural lumbar cord stimulation. Exp Brain Res 154(3):308–326
Garara B, Wood A, Marcus HJ, Tsang K, Wilson MH, Khan M (2016) Intramuscular diaphragmatic stimulation for patients with traumatic high cervical injuries and ventilator dependent respiratory failure: a systematic review of safety and effectiveness. Injury 47(3):539–544
Kaufman MR et al (2015) Diaphragmatic reinnervation in ventilator-dependent patients with cervical spinal cord injury and concomitant phrenic nerve lesions using simultaneous nerve transfers and implantable neurostimulators. J Reconstr Microsurg 31(5):391–395
Posluszny JA Jr et al (2014) Multicenter review of diaphragm pacing in spinal cord injury: successful not only in weaning from ventilators but also in bridging to independent respiration. J Trauma Acute Care Surg 76(2):303–309 discussion 309–10
Dalal K, DiMarco AF (2014) Diaphragmatic pacing in spinal cord injury. Phys Med Rehabil Clin N Am 25(3):619–629 viii
Nandra KS, Harari M, Price TP, Greaney PJ, Weinstein MS (2017) Successful reinnervation of the diaphragm after intercostal to phrenic nerve neurotization in patients with high spinal cord injury. Ann Plast Surg 79(2):180–182
Krieger LM, Krieger AJ (2000) The intercostal to phrenic nerve transfer: an effective means of reanimating the diaphragm in patients with high cervical spine injury. Plast Reconstr Surg 105(4):1255–1261
Martens FM, Heesakkers JP (2011) Clinical results of a brindley procedure: sacral anterior root stimulation in combination with a rhizotomy of the dorsal roots. Ther Adv Urol 2011:709708
Van Kerrebroeck PE et al (1996) Results of the treatment of neurogenic bladder dysfunction in spinal cord injury by sacral posterior root rhizotomy and anterior sacral root stimulation. J Urol 155(4):1378–1381
Brindley GS, Polkey CE, Rushton DN, Cardozo L (1986) Sacral anterior root stimulators for bladder control in paraplegia: the first 50 cases. J Neurol Neurosurg Psychiatry 49(10):1104–1114
Brindley GS, Polkey CE, Rushton DN (1982) Sacral anterior root stimulators for bladder control in paraplegia. Paraplegia 20(6):365–381
Brindley GS (1994) The first 500 patients with sacral anterior root stimulator implants: general description. Paraplegia 32(12):795–805
MacDonagh RP, Sun WM, Smallwood R, Forster D, Read NW (1990) Control of defecation in patients with spinal injuries by stimulation of sacral anterior nerve roots. BMJ 300(6738):1494–1497
Hansen J et al (2005) Treatment of neurogenic detrusor overactivity in spinal cord injured patients by conditional electrical stimulation. J Urol 173(6):2035–2039
Hamel O, Perrouin-Verbe B, Robert R (2004) Brindley technique with intradural deafferentation and extradural implantation by a single sacral laminectomy. Neurochirurgie 50(6):661–666
Sauerwein D, Ingunza W, Fischer J, Madersbacher H, Polkey CE, Brindley GS, Colombel P, Teddy P (1990) Extradural implantation of sacral anterior root stimulators. J Neurol Neurosurg Psychiatry 53(8):681–684
Possover M (2014) The LION procedure to the pelvic nerves for treatment of urinary and faecal disorders. Surg Technol Int 24:225–230
Possover M (2009) The sacral LION procedure for recovery of bladder/rectum/sexual functions in paraplegic patients after explantation of a previous Finetech-Brindley controller. J Minim Invasive Gynecol 16(1):98–101
Onders RP, Elmo MJ, Khansarinia S, Bowman B, Yee J, Road J, Bass B, Dunkin B, Ingvarsson PE, Oddsdóttir M (2009) Complete worldwide operative experience in laparoscopic diaphragm pacing: results and differences in spinal cord injured patients and amyotrophic lateral sclerosis patients. Surg Endosc 23(7):1433–1440
Tetzlaff W, Okon EB, Karimi-Abdolrezaee S, Hill CE, Sparling JS, Plemel JR, Plunet WT, Tsai EC, Baptiste D, Smithson LJ, Kawaja MD, Fehlings MG, Kwon BK (2011) A systematic review of cellular transplantation therapies for spinal cord injury. J Neurotrauma 28(8):1611–1682
Nagoshi N, Nakashima H, Fehlings MG (2015) Riluzole as a neuroprotective drug for spinal cord injury: from bench to bedside. Molecules 20(5):7775–7789
Adeeb N, Mortazavi MM (2014) The role of FGF2 in spinal cord trauma and regeneration research. Brain Behav 4(2):105–107
Satkunendrarajah K, Nassiri F, Karadimas SK, Lip A, Yao G, Fehlings MG (2016) Riluzole promotes motor and respiratory recovery associated with enhanced neuronal survival and function following high cervical spinal hemisection. Exp Neurol 276:59–71
Fehlings MG, Nakashima H, Nagoshi N, Chow DSL, Grossman RG, Kopjar B (2016) Rationale, design and critical end points for the Riluzole in Acute Spinal Cord Injury Study (RISCIS): a randomized, double-blinded, placebo-controlled parallel multi-center trial. Spinal Cord 54(1):8–15
Fan X et al (2017) Stem cell transplantation for spinal cord injury: a meta-analysis of treatment effectiveness and safety. Neural Regen Res 12(5):815–825
Kothari M, Goel A (2013) The stem cell promise: the future of stemocytology. J Craniovertebr Junction Spine 4(2):47–48
Svendsen C (2002) Stem cells: hype or hope? Drug Discov Today 7(8):455–456
Anna Z, Katarzyna JW (2017) Therapeutic potential of olfactory ensheathing cells and mesenchymal stem cells in spinal cord injuries. Stem Cells Int 2017:3978595
Park JH, Kim DY, Sung IY, Choi GH, Jeon MH, Kim KK, Jeon SR (2012) Long-term results of spinal cord injury therapy using mesenchymal stem cells derived from bone marrow in humans. Neurosurgery 70(5):1238–1247 discussion 1247
Goel A (2016) Stem cell therapy in spinal cord injury: hollow promise or promising science? J Craniovertebr Junction Spine 7(2):121–126
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Quadri, S.A., Farooqui, M., Ikram, A. et al. Recent update on basic mechanisms of spinal cord injury. Neurosurg Rev 43, 425–441 (2020). https://doi.org/10.1007/s10143-018-1008-3
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DOI: https://doi.org/10.1007/s10143-018-1008-3