The impact of walking on spinal cord tissue regeneration in patients with paraplegia following spinal cord injury

  • Adela Mileti Physiotherapist
Keywords: “SCI”, “neuroplasticity”, “regeneration”, “paraplegia”, “proprioception” and “gait training”


The impact of walking in Spinal Cord Injury can promote axonal growth through directed neuroplasticity. The impact of walking in corticospinal tracts, in combination with proprioception, could be the key to neuroregeneration. Furthermore, growth factors such as brain-derived neurotrophic factor (BDNF) and insulin growth factor -1 (IGF-1) play a crucial role not only in the procedure of axonal growth but also in the remyelination.

Many posttraumatic treatment strategies have been evaluated until now, including pharmacological agents aimingto block the development of secondary apoptotic mechanisms of CNS. The same strategies are simultaneously able to promote the regeneration of neuroaxons. Nevertheless, there is insufficient knowledge concerning the hypothesis that gait training could be applied as a potential therapy for neuroprotection following SCI.

The objective of this review is to assess the impact of assisted walking in paraplegia by consolidating evidence regarding: (a) neuroplasticity (b) tissue regeneration.


Download data is not yet available.


Rossignol S, Schwab M, Schwartz M, et al.Spinal Cord Injury: Time to move? Journal of Neuroscience 31 October 2007; 27(44):11782-92

McKinley W, Santos K, Meade M, et al. Incidence and outcomes of spinal cord injury clinical syndromes. The journal of spinal cord medicine 2007;30(3): 215-24.

Filli L, Schwab ME. Structural and functional reorganization of propriospinal connections promotes functional recovery after spinal cord injury. Neural RegenRes. 2015;10(4):509-13.

Yang B, Zhang F, Cheng F, et al. Strategies and prospects of effective neural circuit reconstruction after spinal cord injury. Cell Death Dis 2020;11:439

Ahuja CS, Fehlings M. Concise Review: Bridging the Gap: Novel Neuroregenerative and Neuroprotective Strategies in Spinal Cord Injury. Stem Cells Transl Med. 2016; doi: 10.5966/sctm.2015-0381 Epub 2016 Apr 29.

Webb AA, Ngan S, Fowler JD. Spinal cord injury I: A synopsis of the basic science. Can Vet J. 2010;51(5):485-92.

Onifer SM, Smith GM, FouadK. Plasticity after Spinal Cord Injury: Relevance to Recovery and Approaches to Facilitate It. Neurotherapeutics 2011;8:283–293.

Gassert R, Dietz V. Rehabilitation robots for the treatment of sensorimotor deficits: a neurophysiological perspective. J NeuroengRehabil. 2018;15(1):46

Grau JW, Huie JR, Lee KH, et al.Metaplasticity and behavior: how training and inflammation affect plastic potential within the spinal cord and recovery after injury. Front Neural Circuits. 2014;8:100.

De Leon RD, Roy RR, Edgerton VR. Is the recovery of stepping following spinal cord injury mediated by modifying existing neural pathways or by generating new pathways? A perspective. Physical Therapy 2001; 81(12):1904-1911.

Khan AS, Livingstone DC, Hurd CL, et al. Retraining walking over ground in a powered exoskeleton after spinal cord injury: a prospective cohort study to examine functional gains and neuroplasticity. J NeuroengRehabil. 2019;1:145.

O’Dell DR, Weber KA, Berliner JC, et al. Midsagittal tissue bridges are associated with walking ability in incomplete spinal cord injury: A magnetic resonance imaging case series. J Spinal Cord Med. 2020; doi: 10.1080

/10790268.2018.1527079 Epub 2018 Oct 22.

Zieriacks A, Aach M, Brinkemper A, et al. Rehabilitation of Acute Vs. Chronic Patients with Spinal Cord Injury with a Neurologically Controlled Hybrid Assistive Limb Exoskeleton: Is There a Difference in Outcome? Front Neurorobot. 202;15:728327.

Donovan J, Kirshblum S. Clinical Trials in Traumatic Spinal Cord Injury. Neurotherapeutics 2018;15:654–68.

Huntemer-Silveira A, Patil N, Brickner MA, et al.Strategies for Oligodendrocyte and Myelin Repair in Traumatic CNS Injury. Front. Cell. Neurosci. 2021;14:619707.

Nagappan PG, Chen H, WangDY. Neuroregeneration and plasticity: a review of the physiological mechanisms for achieving functional recovery postinjury. Military Med Res2020;7:30.

Ahuja CS, Nori S, Tetreault L, et al. Traumatic Spinal Cord Injury-Repair and Regeneration. Neurosurgery. 2017;80(3):9-22.

Dietz V, Fouad K. Restoration of sensorimotor functions after spinal cord injury. Brain 2014;137(3): 654-667.

Behrman AL, Bowden MG, Nair PM. Neuroplasticity after spinal cord injury and training: an emerging paradigm shift in rehabilitation and walking recovery. Physical therapy 2006;86(10):1406-1425.

Carro E, NuñezA, Busiguina S, et al. Circulating insulin-like growth factor I mediate effects of exercise on the brain. Journal of Neuroscience 2000;20(8): 2926-2933.

DingQ, Vaynman S, Akhavan M, et al. Insulin-like growth factor I interface with brain-derived neurotrophic factor-mediated synaptic plasticity to modulate aspects of exercise-induced cognitive function. Neuroscience 2006; 140(3):823-33.

Zhang L, Lin F, Sun L, et al. Comparison of Efficacy of Lokomat and Wearable Exoskeleton-Assisted Gait Training in People with Spinal Cord Injury: A Systematic Review and Network Meta-Analysis. Front Neurol. 2022;13:772660.

Zheng Y, Mao YR, Yuan TF, et al. Multimodal treatment for spinal cord injury: a sword of neuroregeneration upon neuromodulation. Neural Regen Res. 2020;15(8):1437-50.

Shah M, Peterson C, Yilmaz E, et al. Current advancements in the management of spinal cord injury: A comprehensive review of literature. Surg Neurol Int. 2020;11:2.

Stevenson AJ, Mrachacz-Kersting N, van Asseldonk E, et al. Spinal plasticity in robot-mediated therapy for the lower limbs. J NeuroengRehabil. 2015;12:81.

Hopf A, Schaefer DJ, Kalbermatten DF, et al. Schwann Cell-Like Cells: Origin and Usability for Repair and Regeneration of the Peripheral and Central Nervous System. Cells. 2020; 9(9):1990.

Wirz M, Zemon DH, Rupp R, et al. Effectiveness of automated locomotor training in patients with chronic incomplete spinal cord injury: a multicenter trial. Archives of physical medicine and rehabilitation 2005; 86(4):672-680.

Leech KA, Hornby TG. High-Intensity Locomotor Exercise Increases Brain-Derived Neurotrophic Factor in Individuals with Incomplete Spinal Cord Injury. J Neurotrauma. 2017;doi: 10.1089/neu.2016.4532 Epub 2017 Jan 18.

KwonBK, Fisher CG, Dvorak MF, et al. Strategies to Promote Neural Repair and Regeneration After Spinal Cord Injury. Spine2005;30(17): 3-13

Pearse DD, Pereira FC, Marcillo AE, et al. cAMP and Schwann cells promote axonal growth and functional recovery after spinal cord injury. Nat Med. 2004;doi: 10.1038/nm1056 Epub 2004 May 23.

Watson RA, Yeung TM. What is the potential of oligodendrocyte progenitor cells to successfully treat human spinal cord injury?BMC Neurol 2011;11:113.

Li N, Leung GK. Oligodendrocyte Precursor Cells in Spinal Cord Injury: A Review and Update. Biomed Res Int. 2015; doi: 10.1155/2015/235195 Epub 2015 Sep 27.

Jiang YQ, Armada K, Martin JH. Neuronal activity and microglial activation support corticospinal tract and proprioceptive afferent sprouting in spinal circuits after a corticospinal system lesion. Exp Neurol. 2019; doi: 10.1016/j. expneurol.2019.113015 Epub 2019 Jul 18.

DietzV, Müller R, Colombo G. Locomotor activity in spinal man: significance of afferent input from joint and load receptors. Brain 2002; 125(12):2626-34.

Shin JC, Jeon HR, Kim D, et al. Effects on the Motor Function, Proprioception, Balance, and Gait Ability of the End-Effector Robot-Assisted Gait Training for Spinal Cord Injury Patients. Brain Sciences. 2021;11(10):1281.

Zehr EP. Neural control of rhythmic human movement: the common core hypothesis. Exerc Sport Sci Rev. 2005;33(1):54-60.

Dietz V. Proprioception and locomotor disorders. Nature Reviews Neuroscience 2002; 3(10):781-790.

Qaiser T, Eginyan G, Chan F, et al. The sensorimotor effects of a lower limb proprioception training intervention in individuals with a spinal cord injury. J Neurophysiol. 2019; doi:10.1152/jn.00842.2018 Epub 2019 Oct 30.

Dietz V, Harkema SJ. Locomotor activity in spinal cord-injured persons. Journal of Applied Physiology 2004;96(5):1954-60.

Dietz V, Colombo G, Jensen L, et al.Locomotor capacity of spinal cord in paraplegic patients. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society 1995;37(5):574-82.

Smith AC, Mummidisetty CK, Rymer WZ, et al. Locomotor training alters the behavior of flexor reflexes during walking in human spinal cord injury. J Neurophysiol. 2014; doi:10.1152/jn.00308.2014 Epub 2014 Aug 13.

Clark DJ. Automaticity of walking: functional significance, mechanisms, measurement and rehabilitation strategies. Front Hum Neurosci. 2015;9:246.

Hubli M, Dietz V. The physiological basis of neurorehabilitation--locomotor training after spinal cord injury. J NeuroengRehabil. 2013;10:5.

Ivanenko YP, Poppele RE, Lacquaniti F. Five basic muscle activation patterns account for muscle activity during human locomotion. J Physiol. 2004; doi: 10.1113/jphysiol.2003.057174 Epub 2004 Jan 14.

Hayes SC, White M, Wilcox CRJ, et al. Biomechanical differences between able-bodied and spinal cord injured individuals walking in an overground robotic exoskeleton. PLoS One. 2022 Jan 27;17(1):e0262915.

Dietz V, Müller R. Degradation of neuronal function following a spinal cord injury: mechanisms and countermeasures. Brain 2004; 127(10):2221-31.

Grau JW, Baine RE, Bean PA, et al. Learning to promote recovery after spinal cord injury. Exp Neurol. 2020;doi: 10.1016/j.expneurol.2020.113334 Epub 2020 Apr 28.

Smith GM, Falone AE, Frank E. Sensory axon regeneration: rebuilding functional connections in the spinal cord. Trends Neurosci. 2012; doi:10.1016/j.tins.2011.10.006 Epub 2011 Nov 30.

Khan AS, Patrick SK, Roy FD, et al. Training-Specific Neural Plasticity in Spinal Reflexes after Incomplete Spinal Cord Injury. Neural Plast. 2016; doi: 10.1155/2016/6718763 Epub 2016 Sep 20.

Smith AC, Knikou M. A Review on Locomotor Training after Spinal Cord Injury: Reorganization of Spinal Neuronal Circuits and Recovery of Motor Function. Neural Plast. 2016; doi: 10.1155/2016/1216258 Epub 2016 May 11.

Knikou M, Mummidisetty CK. Locomotor training improves premotoneuronal control after chronic spinal cord injury. J Neurophysiol. 2014;111(11):2264-75. doi: 10.1152/jn.00871.2013 Epub 2014 Mar 5.

Smith AC, Rymer WZ, Knikou M. Locomotor training modifies soleus monosynaptic motoneuron responses in human spinal cord injury. Exp Brain Res. 2015; doi: 10.1007/s00221-014-4094-7 Epub 2014 Sep 10.

Zholudeva LV, Abraira VE, Satkunendrarajah K, et al. Spinal Interneurons as Gatekeepers to Neuroplasticity after Injury or Disease. J Neurosci. 2021; doi: 10.1523/Jneuroscience.1654-20.2020 Epub 2021 Jan 20.

Knikou M, Smith AC, Mummidisetty CK. Locomotor training improves reciprocal and nonreciprocal inhibitory control of soleus motoneurons in human spinal cord injury. Journal of Neurophysiology 2015; 113(7):2447-60.

Mirbagheri MM, Tsao C, Pelosin E, et al. Therapeutic effects of robotic-assisted locomotor training on neuromuscular properties. In 9th International Conference on Rehabilitation Robotics, 2005. ICORR 2005. (pp. 561-564). IEEE.

Alamro RA, Chisholm AE, Williams AMM, et al. Overground walking with a robotic exoskeleton elicits trunk muscle activity in people with high-thoracic motor-complete spinal cord injury. J NeuroengRehabil. 2018;15(1):109.

Sczesny-Kaiser M, Höffken O, Aach M, et al. HAL® exoskeleton training improves walking parameters and normalizes cortical excitability in primary somatosensory cortex in spinal cord injury patients. J NeuroengRehabil. 2015;12:68.

Calabrò RS, Naro A, Leo A, et al. Usefulness of robotic gait training plus neuromodulation in chronic spinal cord injury: a case report. J Spinal Cord Med. 2017; doi: 10.1080/10790268.2016.1153275 Epub 2016 Mar 4.

Shin JC, Kim JY, Park HK, et al. Effect of robotic-assisted gait training in patients with incomplete spinal cord injury. Ann Rehabil Med. 2014; doi: 10.5535/arm.2014.38.6.719 Epub 2014 Dec 24.

Nam KY, Kim HJ, Kwon BS, et al. Robot-assisted gait training (Lokomat) improves walking function and activity in people with spinal cord injury: a systematic review. J NeuroengRehabil. 2017; doi: 10.1186/s12984-017-0232-3.

Dobkin BH, Apple D, Barbeau H, et al. Methods for a Randomized Trial of Weight-Supported Treadmill Training Versus Conventional Training for Walking During Inpatient Rehabilitation after Incomplete Traumatic Spinal Cord Injury. Neurorehabilitation and Neural Repair. 2003; 17(3):153-67.

Field-Fote EC, Yang JF, Basso DM, et al. Supraspinal Control Predicts Locomotor Function and Forecasts Responsiveness to Training after Spinal Cord Injury. J Neurotrauma. 2017; doi: 10.1089/neu.2016.4565 Epub 2016 Dec 20.

Barthélemy D, Knudsen H, Willerslev-Olsen M, et al. Functional implications of corticospinal tract impairment on gait after spinal cord injury. Spinal Cord 2013; 51: 852–56.

Knikou M. Plasticity of corticospinal neural control after locomotor training in human spinal cord injury. Neural Plast. 2012; doi: 10.1155/2012/254948 Epub 2012 Jun 4.

Oudega M, Perez MA. Corticospinal reorganization after spinal cord injury. J Physiol. 2012; doi: 10.1113/jphysiol.2012.233189 Epub 2012 May 14.

Querry RG, Pacheco F, Annaswamy T, et al. Synchronous stimulation and monitoring of soleus H reflex during robotic body weight-supported ambulation in subjects with spinal cord injury. Journal of Rehabilitation Research & Development 2008;45(1).

Blicher JU, Nielsen JF. Cortical and spinal excitability changes after robotic gait training in healthy participants. Neurorehabilitation and neural repair 2009; 23(2):143-49.

Thomas SL, Gorassini MA. Increases in corticospinal tract function by treadmill training after incomplete spinal cord injury. Journal of neurophysiology 2005; 94(4):2844-55.

Winchester P, McColl R, Querry R, et al. Changes in supraspinal activation patterns following robotic locomotor therapy in motor-incomplete spinal cord injury. Neurorehabilitation and neural repair 2005; 19(4):313-24.

Blecher R, Heinemann-Yerushalmi L, Assaraf E, et al. New functions for the proprioceptive system in skeletal biology. Philos Trans R Soc Lond B Biol Sci. 2018; 373(1759):20170327.

MacKinnon CD. Sensorimotor anatomy of gait, balance, and falls. Handb Clin Neurol. 2018; 159:3-26.

Takakusaki K. Functional Neuroanatomy for Posture and Gait Control. J Mov Disord. 2017;10(1):1-17.

Hillier S, Immink M, Thewlis D. Assessing Proprioception: A Systematic Review of Possibilities. Neurorehabilitation and Neural Repair. 2015; 29(10):933-49.

Domingo A, Lam T. Reliability and validity of using the Lokomat to assess lower limb joint position sense in people with incomplete spinal cord injury. J NeuroengRehabil. 2014;11:167.

Angeli CA, Edgerton VR, Gerasimenko YP, et al. Altering spinal cord excitability enables voluntary movements after chronic complete paralysis in humans. Brain. 2014 doi: 10.1093/brain/awu038 Epub 2014 Apr 8.

Dietz V, Curt A. Neurological aspects of spinal cord repair: promises and challenges. Lancet Neurol. 2006;5(8):688-94.

Fink KL, Cafferty WB. Reorganization of Intact Descending Motor Circuits to Replace Lost Connections after Injury. Neurotherapeutics. 2016; 13(2):370-81.