Rehabilitative training and plasticity following spinal cord injury

Rehabilitative training is currently one of the most successful treatments to promote functional recovery following spinal cord injury. Nevertheless, there are many unanswered questions including the most effective and beneficial design, and the mechanisms underlying the training effects on motor recovery. Furthermore, rehabilitative training will certainly be combined with pharmacological treatments developed to promote the "repair" of the injured spinal cord. Thus, insight into training-induced mechanisms will be of great importance to fine tune such combined treatments. In this review we address current challenges of rehabilitative training and mechanisms involved in promoting motor recovery with the focus on animal models. These challenges suggest that although rehabilitative training appears to be a relatively straight forward treatment approach, more research is needed to optimize its effect on functional outcome in order to enhance our chances of success when combining pharmacological treatments promoting axonal growth and rehabilitative training in the clinic.

[1]  P. London.  Injury , 1969, Definitions.

[2]  Jeff Biernaskie,et al.  Enriched Rehabilitative Training Promotes Improved Forelimb Motor Function and Enhanced Dendritic Growth after Focal Ischemic Injury , 2001, The Journal of Neuroscience.

[3]  Wolfram Tetzlaff,et al.  Proximal and distal impairments in rat forelimb use in reaching follow unilateral pyramidal tract lesions , 1993, Behavioural Brain Research.

[4]  Adam R Ferguson,et al.  Two chronic motor training paradigms differentially influence acute instrumental learning in spinally transected rats , 2007, Behavioural Brain Research.

[5]  K. Fouad,et al.  Cervical sprouting of corticospinal fibers after thoracic spinal cord injury accompanies shifts in evoked motor responses , 2001, Current Biology.

[6]  T. A. Thrasher,et al.  Functional electrical stimulation of walking: function, exercise and rehabilitation. , 2008, Annales de readaptation et de medecine physique : revue scientifique de la Societe francaise de reeducation fonctionnelle de readaptation et de medecine physique.

[7]  C. Heckman,et al.  Effects of exercise training on -motoneurons , 2006 .

[8]  A Curt,et al.  How does the human brain deal with a spinal cord injury? , 1998, The European journal of neuroscience.

[9]  H. Thoenen.  Neurotrophins and Neuronal Plasticity , 1995, Science.

[10]  D. Burke,et al.  Swim Training Initiated Acutely after Spinal Cord Injury Is Ineffective and Induces Extravasation In and Around the Epicenter , 2009 .

[11]  P. Carrive,et al.  Effect of Treadmill Training on Autonomic Dysreflexia in Spinal Cord—Injured Rats , 2009, Neurorehabilitation and neural repair.

[12]  F. Lacquaniti,et al.  Recovery of forward stepping in spinal cord injured patients does not transfer to untrained backward stepping , 2004, Experimental Brain Research.

[13]  H. Barbeau,et al.  Influence of body weight support on normal human gait: development of a gait retraining strategy. , 1991, Physical therapy.

[14]  E. Taub,et al.  Constraint-Induced Movement Therapy: a new family of techniques with broad application to physical rehabilitation--a clinical review. , 1999, Journal of rehabilitation research and development.

[15]  Wen-Jie Song,et al.  Plasticity of neuronal connections in developing brains of mammals , 1992, Neuroscience Research.

[16]  J. Rodger,et al.  cAMP regulates axon outgrowth and guidance during optic nerve regeneration in goldfish , 2005, Molecular and Cellular Neuroscience.

[17]  K. Fouad,et al.  Electrical stimulation of intact peripheral sensory axons in rats promotes outgrowth of their central projections , 2008, Experimental Neurology.

[18]  Stierlin.  Organization of Behavior. A Neuropsychological Theory , 1953 .

[19]  D. Burke,et al.  Task-specificity vs. ceiling effect: Step-training in shallow water after spinal cord injury , 2010, Experimental Neurology.

[20]  M. Lemay,et al.  Neurotrophic factors promote and enhance locomotor recovery in untrained spinalized cats. , 2007, Journal of neurophysiology.

[21]  C H Shea,et al.  Composition of practice: influence on the retention of motor skills. , 1991, Research quarterly for exercise and sport.

[22]  Daniel Cattaert,et al.  Down-regulation of the potassium-chloride cotransporter KCC2 contributes to spasticity after spinal cord injury , 2010, Nature Medicine.

[23]  D. Hubel,et al.  EFFECTS OF VISUAL DEPRIVATION ON MORPHOLOGY AND PHYSIOLOGY OF CELLS IN THE CATS LATERAL GENICULATE BODY. , 1963, Journal of neurophysiology.

[24]  M. Gorassini,et al.  Reduced functional recovery by delaying motor training after spinal cord injury. , 2005, Journal of neurophysiology.

[25]  C. Shatz,et al.  Synaptic Activity and the Construction of Cortical Circuits , 1996, Science.

[26]  K. Fouad,et al.  Advantages of delaying the onset of rehabilitative reaching training in rats with incomplete spinal cord injury , 2009, The European journal of neuroscience.

[27]  Monica A. Gorassini,et al.  Effects of transcranial direct current stimulation on the excitability of the leg motor cortex , 2007, Experimental Brain Research.

[28]  M Hallett,et al.  Topographic maps of human motor cortex in normal and pathological conditions: mirror movements, amputations and spinal cord injuries. , 1991, Electroencephalography and clinical neurophysiology. Supplement.

[29]  G. W. Hiebert,et al.  BDNF promotes connections of corticospinal neurons onto spared descending interneurons in spinal cord injured rats. , 2006, Brain : a journal of neurology.

[30]  Richard B. Stein,et al.  Does Functional Electrical Stimulation for Foot Drop Strengthen Corticospinal Connections? , 2010, Neurorehabilitation and neural repair.

[31]  Samar Hamid,et al.  Role of electrical stimulation for rehabilitation and regeneration after spinal cord injury: an overview , 2008, European Spine Journal.

[32]  K. Beekhuizen.  New Perspectives on Improving Upper Extremity Function after Spinal Cord Injury , 2005, Journal of neurologic physical therapy : JNPT.

[33]  W. Alilain,et al.  Increased chondroitin sulfate proteoglycan expression in denervated brainstem targets following spinal cord injury creates a barrier to axonal regeneration overcome by chondroitinase ABC and neurotrophin-3 , 2008, Experimental Neurology.

[34]  J. Donoghue,et al.  Plasticity and primary motor cortex. , 2000, Annual review of neuroscience.

[35]  M. Gorassini,et al.  Increases in corticospinal tract function by treadmill training after incomplete spinal cord injury. , 2005, Journal of neurophysiology.

[36]  D. Hubel,et al.  RECEPTIVE FIELDS OF CELLS IN STRIATE CORTEX OF VERY YOUNG, VISUALLY INEXPERIENCED KITTENS. , 1963, Journal of neurophysiology.

[37]  Adam R Ferguson,et al.  BDNF and learning: Evidence that instrumental training promotes learning within the spinal cord by up-regulating BDNF expression , 2007, Neuroscience.

[38]  Jian Liu,et al.  Neural plasticity after spinal cord injury , 2012, Neural regeneration research.

[39]  M. Schwab,et al.  Brain-derived neurotrophic factor supports the survival of cultured rat retinal ganglion cells , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[40]  L. Cohen,et al.  Effects of non-invasive cortical stimulation on skilled motor function in chronic stroke. , 2005, Brain : a journal of neurology.

[41]  J. Steeves,et al.  Brain‐derived neurotrophic factor applied to the motor cortex promotes sprouting of corticospinal fibers but not regeneration into a peripheral nerve transplant , 2002, Journal of neuroscience research.

[42]  O. Arancio,et al.  Neurotrophins, synaptic plasticity and dementia , 2007, Current Opinion in Neurobiology.

[43]  V. Edgerton,et al.  Use-Dependent Modulation of Inhibitory Capacity in the Feline Lumbar Spinal Cord , 2002, The Journal of Neuroscience.

[44]  G. Dudley,et al.  Weight-supported treadmill vs over-ground training for walking after acute incomplete SCI , 2006, Neurology.

[45]  John H. Martin,et al.  Chronic Electrical Stimulation of the Intact Corticospinal System after Unilateral Injury Restores Skilled Locomotor Control and Promotes Spinal Axon Outgrowth , 2010, The Journal of Neuroscience.

[46]  V. Dietz,et al.  Adaptational effects during human split-belt walking: influence of afferent input , 1998, Experimental Brain Research.

[47]  K. Pearson,et al.  Adaptive Locomotor Plasticity in Chronic Spinal Cats after Ankle Extensors Neurectomy , 2001, The Journal of Neuroscience.

[48]  F. Gomez-Pinilla,et al.  License to Run: Exercise Impacts Functional Plasticity in the Intact and Injured Central Nervous System by Using Neurotrophins , 2005, Neurorehabilitation and neural repair.

[49]  John H. Martin,et al.  Electrical Stimulation of Spared Corticospinal Axons Augments Connections with Ipsilateral Spinal Motor Circuits after Injury , 2007, The Journal of Neuroscience.

[50]  Richard B. Stein,et al.  Electrical stimulation of the human common peroneal nerve elicits lasting facilitation of cortical motor-evoked potentials , 2003, Experimental Brain Research.

[51]  Training-induced plasticity in rats with cervical spinal cord injury: Effects and side effects , 2010, Behavioural Brain Research.

[52]  V. Edgerton,et al.  BDNF–exercise interactions in the recovery of symmetrical stepping after a cervical hemisection in rats , 2008, Neuroscience.

[53]  A. Wernig,et al.  Laufband locomotion with body weight support improved walking in persons with severe spinal cord injuries , 1992, Paraplegia.

[54]  Mark Speechley,et al.  Evidence-Based Review of Stroke Rehabilitation: Executive Summary, 12th Edition , 2009, Topics in stroke rehabilitation.

[55]  V. Dietz,et al.  Degradation of neuronal function following a spinal cord injury: mechanisms and countermeasures. , 2004, Brain : a journal of neurology.

[56]  Tessa Gordon,et al.  Brief electrical stimulation accelerates axon regeneration in the peripheral nervous system and promotes sensory axon regeneration in the central nervous system. , 2009, Motor control.

[57]  V. Dietz,et al.  Treadmill training in incomplete spinal cord injured rats , 2000, Behavioural Brain Research.

[58]  S. Harkema,et al.  Retraining the injured spinal cord , 2001, The Journal of physiology.

[59]  Igor A. Lavrov,et al.  Transformation of nonfunctional spinal circuits into functional states after the loss of brain input , 2009, Nature Neuroscience.

[60]  A. Behrman,et al.  Acute Effects Of Locomotor Training on Overground Walking Speed and H-Reflex Modulation in Individuals with Incomplete Spinal Cord Injury , 2001, The journal of spinal cord medicine.

[61]  Zhe Ying,et al.  Three exercise paradigms differentially improve sensory recovery after spinal cord contusion in rats. , 2004, Brain : a journal of neurology.

[62]  V Reggie Edgerton,et al.  Differential effects of anti-Nogo-A antibody treatment and treadmill training in rats with incomplete spinal cord injury. , 2009, Brain : a journal of neurology.

[63]  W. McIlroy,et al.  Adaptation in the motor cortex following cervical spinal cord injury , 2002, Neurology.

[64]  G. Muir,et al.  Effects of combined dorsolateral and dorsal funicular lesions on sensorimotor behaviour in rats , 2008, Experimental Neurology.

[65]  J. Duysens,et al.  Significance of load receptor input during locomotion: a review. , 2000, Gait & posture.

[66]  D O Frost,et al.  BDNF/trkB signaling in the developmental sculpting of visual connections. , 2001, Progress in brain research.

[67]  Mriganka Sur,et al.  Visual activity and cortical rewiring: activity-dependent plasticity of cortical networks. , 2006, Progress in brain research.

[68]  Martin E Schwab,et al.  The injured spinal cord spontaneously forms a new intraspinal circuit in adult rats , 2004, Nature Neuroscience.

[69]  J. Fawcett,et al.  Chondroitinase ABC treatment opens a window of opportunity for task-specific rehabilitation , 2009, Nature Neuroscience.

[70]  D. Hubel,et al.  SINGLE-CELL RESPONSES IN STRIATE CORTEX OF KITTENS DEPRIVED OF VISION IN ONE EYE. , 1963, Journal of neurophysiology.

[71]  V. Edgerton,et al.  Exercise restores levels of neurotrophins and synaptic plasticity following spinal cord injury , 2005, Experimental Neurology.

[72]  M. Hallett,et al.  Modulation of motor cortical outputs to the reading hand of braille readers , 1993, Annals of neurology.

[73]  K. Maccorquodale.  Organization of Behavior : A Neuropsychological Theory , 1951 .

[74]  J. Krakauer.  Motor learning: its relevance to stroke recovery and neurorehabilitation. , 2006, Current opinion in neurology.

[75]  J. Williamson,et al.  Changes in Supraspinal Activation Patterns following Robotic Locomotor Therapy in Motor-Incomplete Spinal Cord Injury , 2005, Neurorehabilitation and neural repair.

[76]  Jaynie F. Yang,et al.  Training of Walking Skills Overground and on the Treadmill: Case Series on Individuals With Incomplete Spinal Cord Injury , 2009, Physical Therapy.

[77]  K. Pearson,et al.  Plasticity in reflex pathways controlling stepping in the cat. , 1997, Journal of neurophysiology.

[78]  Heidi M. Schambra,et al.  Direct Current Stimulation Promotes BDNF-Dependent Synaptic Plasticity: Potential Implications for Motor Learning , 2010, Neuron.

[79]  W. Mellado,et al.  BDNF activates CaMKIV and PKA in parallel to block MAG-mediated inhibition of neurite outgrowth , 2008, Molecular and Cellular Neuroscience.

[80]  V. Reggie Edgerton,et al.  Training locomotor networks , 2008, Brain Research Reviews.

[81]  K. Fouad,et al.  Locomotion after spinal cord injury depends on constitutive activity in serotonin receptors. , 2010, Journal of neurophysiology.

[82]  T. Elbert,et al.  New treatments in neurorehabiliation founded on basic research , 2002, Nature Reviews Neuroscience.

[83]  V R Edgerton,et al.  Hindlimb locomotor and postural training modulates glycinergic inhibition in the spinal cord of the adult spinal cat. , 1999, Journal of neurophysiology.

[84]  Jonathan R Wolpaw,et al.  Reflex conditioning: a new strategy for improving motor function after spinal cord injury , 2010, Annals of the New York Academy of Sciences.

[85]  B. Dobkin,et al.  Human lumbosacral spinal cord interprets loading during stepping. , 1997, Journal of neurophysiology.

[86]  D. Basso,et al.  Injured mice at the gym: Review, results and considerations for combining chondroitinase and locomotor exercise to enhance recovery after spinal cord injury , 2011, Brain Research Bulletin.

[87]  R. Ichiyama,et al.  Movement rehabilitation after spinal cord injuries: Emerging concepts and future directions , 2011, Brain Research Bulletin.

[88]  R. Lemon,et al.  Comparing the function of the corticospinal system in different species: Organizational differences for motor specialization? , 2005, Muscle & nerve.

[89]  Hui Zhong,et al.  Step Training Reinforces Specific Spinal Locomotor Circuitry in Adult Spinal Rats , 2008, The Journal of Neuroscience.

[90]  Keir G Pearson,et al.  Generating the walking gait: role of sensory feedback. , 2004, Progress in brain research.

[91]  R. J. Gregor,et al.  Effects of training on the recovery of full-weight-bearing stepping in the adult spinal cat , 1986, Experimental Neurology.

[92]  A. Konnerth,et al.  Neurotrophin-evoked rapid excitation through TrkB receptors , 1999, Nature.

[93]  V R Edgerton,et al.  Full weight-bearing hindlimb standing following stand training in the adult spinal cat. , 1998, Journal of neurophysiology.

[94]  S. Rossignol,et al.  Recovery of locomotion after chronic spinalization in the adult cat , 1987, Brain Research.

[95]  F. Colbourne,et al.  Rehabilitation after intracerebral hemorrhage in rats improves recovery with enhanced dendritic complexity but no effect on cell proliferation , 2010, Behavioural Brain Research.

[96]  R. Nudo,et al.  Reorganization of movement representations in primary motor cortex following focal ischemic infarcts in adult squirrel monkeys. , 1996, Journal of neurophysiology.

[97]  Serge Rossignol,et al.  Prominent Role of the Spinal Central Pattern Generator in the Recovery of Locomotion after Partial Spinal Cord Injuries , 2008, The Journal of Neuroscience.

[98]  K. Fouad,et al.  Spontaneous locomotor recovery in spinal cord injured rats is accompanied by anatomical plasticity of reticulospinal fibers , 2006, The European journal of neuroscience.

[99]  S. Grillner,et al.  The locomotion of the low spinal cat. I. Coordination within a hindlimb. , 1980, Acta physiologica Scandinavica.

[100]  D. Burke,et al.  Effects of swimming on functional recovery after incomplete spinal cord injury in rats. , 2006, Journal of neurotrauma.

[101]  S. Rossignol,et al.  Locomotor capacities after complete and partial lesions of the spinal cord. , 1996, Acta neurobiologiae experimentalis.

[102]  Jessica K. Alexander,et al.  Neuroinflammation in spinal cord injury: therapeutic targets for neuroprotection and regeneration. , 2009, Progress in brain research.

[103]  J. F. Yang,et al.  Contribution of peripheral afferents to the activation of the soleus muscle during walking in humans , 2004, Experimental Brain Research.

[104]  G. Rousseau,et al.  Training improves the electrophysiological properties of lumbar neurons and locomotion after thoracic spinal cord injury in rats , 2008, Neuroscience Research.

[105]  N. Harel,et al.  Nogo receptor deletion and multimodal exercise improve distinct aspects of recovery in cervical spinal cord injury. , 2010, Journal of neurotrauma.

[106]  J. Gossard,et al.  Step Training-Dependent Plasticity in Spinal Cutaneous Pathways , 2004, The Journal of Neuroscience.

[107]  D. Resnick,et al.  GeneChip® analysis after acute spinal cord injury in rat , 2001, Journal of neurochemistry.

[108]  Serge Rossignol,et al.  Plasticity of locomotor sensorimotor interactions after peripheral and/or spinal lesions , 2008, Brain Research Reviews.

[109]  M. Filbin,et al.  Prior Exposure to Neurotrophins Blocks Inhibition of Axonal Regeneration by MAG and Myelin via a cAMP-Dependent Mechanism , 1999, Neuron.

[110]  M. Bangert,et al.  Mapping perception to action in piano practice: a longitudinal DC-EEG study , 2003, BMC Neuroscience.

[111]  K. Pearson,et al.  Modification of group I field potentials in the intermediate nucleus of the cat spinal cord after chronic axotomy of an extensor nerve , 1997, Neuroscience Letters.

[112]  M. Filbin,et al.  cAMP and Schwann cells promote axonal growth and functional recovery after spinal cord injury , 2004, Nature Medicine.

[113]  A. Wernig,et al.  Weight-supported treadmill vs over-ground training for walking after acute incomplete SCI , 2006, Neurology.

[114]  V. Dietz,et al.  Rehabilitation of locomotion after spinal cord injury. , 2010, Restorative neurology and neuroscience.

[115]  K. Pearson,et al.  Contribution of sensory feedback to the generation of extensor activity during walking in the decerebrate Cat. , 1999, Journal of neurophysiology.

[116]  T. Sinkjaer,et al.  Increase in tibialis anterior motor cortex excitability following repetitive electrical stimulation of the common peroneal nerve , 2002, Experimental Brain Research.

[117]  Charles Tator,et al.  Intrathecal administration of epidermal growth factor and fibroblast growth factor 2 promotes ependymal proliferation and functional recovery after spinal cord injury in adult rats. , 2002, Journal of neurotrauma.

[118]  V. Dietz,et al.  Nogo‐A antibodies and training reduce muscle spasms in spinal cord‐injured rats , 2010, Annals of neurology.

[119]  M. Schwab,et al.  Constraint-Induced Movement Therapy in the Adult Rat after Unilateral Corticospinal Tract Injury , 2008, The Journal of Neuroscience.

[120]  Xiang Yang Chen,et al.  Operant Conditioning of H-Reflex Can Correct a Locomotor Abnormality after Spinal Cord Injury in Rats , 2006, The Journal of Neuroscience.

[121]  B. Kolb,et al.  Immediate constraint-induced movement therapy causes local hyperthermia that exacerbates cerebral cortical injury in rats. , 2004, Canadian journal of physiology and pharmacology.

[122]  M. Tuszynski,et al.  Spontaneous corticospinal axonal plasticity and functional recovery after adult central nervous system injury , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[123]  V. Edgerton,et al.  Changes in Motoneuron Properties and Synaptic Inputs Related to Step Training after Spinal Cord Transection in Rats , 2007, The Journal of Neuroscience.

[124]  Adam R Ferguson,et al.  Instrumental learning within the spinal cord: underlying mechanisms and implications for recovery after injury. , 2006, Behavioral and cognitive neuroscience reviews.

[125]  J. Fung,et al.  The combined effects of clonidine and cyproheptadine with interactive training on the modulation of locomotion in spinal cord injured subjects , 1990, Journal of the Neurological Sciences.

[126]  H. Scharfman,et al.  BDNF and epilepsy: too much of a good thing? , 2001, Trends in Neurosciences.

[127]  T. Perkins,et al.  FES cycling may promote recovery of leg function after incomplete spinal cord injury , 2000, Spinal Cord.

[128]  G. Muir,et al.  Task-dependent compensation after pyramidal tract and dorsolateral spinal lesions in rats , 2009, Experimental Neurology.

[129]  T. Gordon,et al.  cAMP promotes neurite outgrowth and extension through protein kinase A but independently of Erk activation in cultured rat motoneurons , 2008, Neuropharmacology.

[130]  S. Rossignol,et al.  The locomotion of the low spinal cat. II. Interlimb coordination. , 1980, Acta physiologica Scandinavica.

[131]  Dawn L. Merrett,et al.  Reaching training in rats with spinal cord injury promotes plasticity and task specific recovery. , 2007, Brain : a journal of neurology.

[132]  Devin L Jindrich,et al.  OEG implantation and step training enhance hindlimb-stepping ability in adult spinal transected rats. , 2008, Brain : a journal of neurology.

[133]  Marie-H Monfils,et al.  Motor map expansion following repeated cortical and limbic seizures is related to synaptic potentiation. , 2002, Cerebral cortex.

[134]  M. Skup,et al.  Exercise-induced motor improvement after complete spinal cord transection and its relation to expression of brain-derived neurotrophic factor and presynaptic markers , 2009, BMC Neuroscience.

[135]  Jaynie F. Yang,et al.  Changes in locomotor muscle activity after treadmill training in subjects with incomplete spinal cord injury. , 2009, Journal of neurophysiology.