scholarly journals Plasticity of connections underlying locomotor recovery after central and/or peripheral lesions in the adult mammals

2006 ◽  
Vol 361 (1473) ◽  
pp. 1647-1671 ◽  
Author(s):  
Serge Rossignol
Keyword(s):  
Functional Recovery ◽  
Peripheral Nerves ◽  
Adult Animal ◽  
Spinal Injury ◽  
Locomotor Training ◽  
Locomotor Recovery ◽  
Reflex Pathways ◽  
Intrinsic Capacity ◽  
Plastic Changes ◽  
Locomotor Patterns

This review discusses some aspects of plasticity of connections after spinal injury in adult animal models as a basis for functional recovery of locomotion. After reviewing some pitfalls that must be avoided when claiming functional recovery and the importance of a conceptual framework for the control of locomotion, locomotor recovery after spinal lesions, mainly in cats, is summarized. It is concluded that recovery is partly due to plastic changes within the existing spinal locomotor networks. Locomotor training appears to change the excitability of simple reflex pathways as well as more complex circuitry. The spinal cord possesses an intrinsic capacity to adapt to lesions of central tracts or peripheral nerves but, as a rule, adaptation to lesions entails changes at both spinal and supraspinal levels. A brief summary of the spinal capacity of the rat, mouse and human to express spinal locomotor patterns is given, indicating that the concepts derived mainly from work in the cat extend to other adult mammals. It is hoped that some of the issues presented will help to evaluate how plasticity of existing connections may combine with and potentiate treatments designed to promote regeneration to optimize remaining motor functions.

Spinal cord injury: overview of experimental approaches used to restore locomotor activity

2015 ◽  
Vol 26 (4) ◽  
Author(s):  
Marc Fakhoury
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Animal Models ◽  
Axonal Regeneration ◽  
Spinal Injury ◽  
Recovery Process ◽  
Locomotor Training ◽  
Locomotor Recovery ◽  
Collateral Sprouting ◽  
Cord Injury

AbstractSpinal cord injury affects more than 2.5 million people worldwide and can lead to paraplegia and quadriplegia. Anatomical discontinuity in the spinal cord results in disruption of the impulse conduction that causes temporary or permanent changes in the cord’s normal functions. Although axonal regeneration is limited, damage to the spinal cord is often accompanied by spontaneous plasticity and axon regeneration that help improve sensory and motor skills. The recovery process depends mainly on synaptic plasticity in the preexisting circuits and on the formation of new pathways through collateral sprouting into neighboring denervated territories. However, spontaneous recovery after spinal cord injury can go on for several years, and the degree of recovery is very limited. Therefore, the development of new approaches that could accelerate the gain of motor function is of high priority to patients with damaged spinal cord. Although there are no fully restorative treatments for spinal injury, various rehabilitative approaches have been tested in animal models and have reached clinical trials. In this paper, a closer look will be given at the potential therapies that could facilitate axonal regeneration and improve locomotor recovery after injury to the spinal cord. This article highlights the application of several interventions including locomotor training, molecular and cellular treatments, and spinal cord stimulation in the field of rehabilitation research. Studies investigating therapeutic approaches in both animal models and individuals with injured spinal cords will be presented.

scholarly journals Adaptation to slope in locomotor-trained spinal cats with intact and self-reinnervated lateral gastrocnemius and soleus muscles

2020 ◽  
Vol 123 (1) ◽  
pp. 70-89
Author(s):  
Dwight Higgin ◽  
Alexander Krupka ◽  
Omid Haji Maghsoudi ◽  
Alexander N. Klishko ◽  
T. Richard Nichols ◽  
...  
Keyword(s):  
Muscle Activity ◽  
Flat Surface ◽  
Weight Bearing ◽  
Locomotor Training ◽  
Sensorimotor Training ◽  
Spinal Transection ◽  
Lateral Gastrocnemius ◽  
Locomotor Recovery ◽  
Flat Surfaces ◽  
Locomotor Patterns

Sensorimotor training providing motion-dependent somatosensory feedback to spinal locomotor networks restores treadmill weight-bearing stepping on flat surfaces in spinal cats. In this study, we examined if locomotor ability on flat surfaces transfers to sloped surfaces and the contribution of length-dependent sensory feedback from lateral gastrocnemius (LG) and soleus (Sol) to locomotor recovery after spinal transection and locomotor training. We compared kinematics and muscle activity at different slopes (±10° and ±25°) in spinalized cats ( n = 8) trained to walk on a flat treadmill. Half of those animals had their right hindlimb LG/Sol nerve cut and reattached before spinal transection and locomotor training, a procedure called muscle self-reinnervation that leads to elimination of autogenic monosynaptic length feedback in spinally intact animals. All spinal animals trained on a flat surface were able to walk on slopes with minimal differences in walking kinematics and muscle activity between animals with/without LG/Sol self-reinnervation. We found minimal changes in kinematics and muscle activity at lower slopes (±10°), indicating that walking patterns obtained on flat surfaces are robust enough to accommodate low slopes. Contrary to results in spinal intact animals, force responses to muscle stretch largely returned in both SELF-REINNERVATED muscles for the trained spinalized animals. Overall, our results indicate that the locomotor patterns acquired with training on a level surface transfer to walking on low slopes and that spinalization may allow the recovery of autogenic monosynaptic length feedback following muscle self-reinnervation. NEW & NOTEWORTHY Spinal locomotor networks locomotor trained on a flat surface can adapt the locomotor output to slope walking, up to ±25° of slope, even with total absence of supraspinal CONTROL. Autogenic length feedback (stretch reflex) shows signs of recovery in spinalized animals, contrary to results in spinally intact animals.

Treadmill training promotes spinal changes leading to locomotor recovery after partial spinal cord injury in cats

2013 ◽  
Vol 109 (12) ◽  
pp. 2909-2922 ◽  
Author(s):  
Marina Martinez ◽  
Hugo Delivet-Mongrain ◽  
Serge Rossignol
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Treadmill Training ◽  
Locomotor Training ◽  
Locomotor Recovery ◽  
Thoracic Level ◽  
Spinal Circuitry ◽  
Cord Injury ◽  
Locomotor Deficits ◽  
Spinal Hemisection

After a spinal hemisection at thoracic level in cats, the paretic hindlimb progressively recovers locomotion without treadmill training but asymmetries between hindlimbs persist for several weeks and can be seen even after a further complete spinal transection at T13. To promote optimal locomotor recovery after hemisection, such asymmetrical changes need to be corrected. In the present study we determined if the locomotor deficits induced by a spinal hemisection can be corrected by locomotor training and, if so, whether the spinal stepping after the complete spinal cord transection is also more symmetrical. This would indicate that locomotor training in the hemisected period induces efficient changes in the spinal cord itself. Sixteen adult cats were first submitted to a spinal hemisection at T10. One group received 3 wk of treadmill training, whereas the second group did not. Detailed kinematic and electromyographic analyses showed that a 3-wk period of locomotor training was sufficient to improve the quality and symmetry of walking of the hindlimbs. Moreover, after the complete spinal lesion was performed, all the trained cats reexpressed bilateral and symmetrical hindlimb locomotion within 24 h. By contrast, the locomotor pattern of the untrained cats remained asymmetrical, and the hindlimb on the side of the hemisection was still deficient. This study highlights the beneficial role of locomotor training in facilitating bilateral and symmetrical functional plastic changes within the spinal circuitry and in promoting locomotor recovery after an incomplete spinal cord injury.

scholarly journals Intraspinal Grafting of Serotonergic Neurons Modifies Expression of Genes Important for Functional Recovery in Paraplegic Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Krzysztof Miazga ◽  
Hanna Fabczak ◽  
Ewa Joachimiak ◽  
Małgorzata Zawadzka ◽  
Łucja Krzemień-Ojak ◽  
...  
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Functional Recovery ◽  
Serotonergic Neurons ◽  
Locomotor Recovery ◽  
Thoracic Level ◽  
Hindlimb Muscles ◽  
Complete Transection ◽  
Expression Of Genes ◽  
Influence Functional

Serotonin (5-hydroxytryptamine; 5-HT) plays an important role in control of locomotion, partly through direct effects on motoneurons. Spinal cord complete transection (SCI) results in changes in 5-HT receptors on motoneurons that influence functional recovery. Activation of 5-HT2A and 5-HT7 receptors improves locomotor hindlimb movements in paraplegic rats. Here, we analyzed the mRNA of 5-HT2A and 5-HT7 receptors (encoded by Htr2a and Htr7 genes, resp.) in motoneurons innervating tibialis anterior (TA) and gastrocnemius lateralis (GM) hindlimb muscles and the tail extensor caudae medialis (ECM) muscle in intact as well as spinal rats. Moreover, the effect of intraspinal grafting of serotonergic neurons on Htr2a and Htr7 gene expression was examined to test the possibility that the graft origin 5-HT innervation in the spinal cord of paraplegic rats could reverse changes in gene expression induced by SCI. Our results indicate that SCI at the thoracic level leads to changes in Htr2a and Htr7 gene expression, whereas transplantation of embryonic serotonergic neurons modifies these changes in motoneurons innervating hindlimb muscles but not those innervating tail muscles. This suggests that the upregulation of genes critical for locomotor recovery, resulting in limb motoneuron plasticity, might account for the improved locomotion in grafted animals.

scholarly journals Electrophysiology of the Fetal Spinal Cord

1964 ◽  
Vol 47 (5) ◽  
pp. 1003-1022 ◽  
Author(s):  
Ken-Ichi Naka
Keyword(s):  
Peripheral Nerves ◽  
Action Potentials ◽  
Dorsal Root ◽  
Adult Animal ◽  
Good Condition ◽  
Marked Change ◽  
Prenatal Development ◽  
Remarkable Change ◽  
Reflex Discharge ◽  
Root Stimulation

Responses from motoneurons were recorded with microelectrodes, from the spinal cords of kitten fetuses and newborn kittens between 40 days' gestation and a few days after birth. As in the adult animal, intracellularly recorded action potentials by either ortho- or antidromic shocks have two components, "A" and "B" or IS and SD. The action potentials of the adult and immature motoneuron differ mainly in the afterpotentials which are absent in the fetal cell in "good" condition. Repeated stimulation or deterioration of the cell resulted, however, in the appearance of depolarizing and hyperpolarizing afterpotentials. No major differences were found in the mode of anti- or orthodromic invasion of the adult and fetal motoneuron, but the degree of invasion of the soma-dendritic complex may be somewhat less in the fetal cells. The ventral root discharge by dorsal root stimulation could be obtained in the fetus 3 weeks before birth. This reflex discharge was concluded to be monosynaptic. Excitatory postsynaptic potentials, probably monosynaptically activated, could be recorded from inside motoneurons by stimulation of dorsal root or peripheral nerves. The most remarkable change during prenatal development was an increase in the speed and efficacy of the excitatory synaptic potentials which showed a marked change during the last weeks of prenatal life.

Limited functional recovery in rats with complete spinal cord injury after transplantation of whole-layer olfactory mucosa

2010 ◽  
Vol 12 (2) ◽  
pp. 122-130 ◽  
Author(s):  
Masanori Aoki ◽  
Haruhiko Kishima ◽  
Kazuhiro Yoshimura ◽  
Masahiro Ishihara ◽  
Masaki Ueno ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Lamina Propria ◽  
Motor Function ◽  
Functional Recovery ◽  
Olfactory Mucosa ◽  
Respiratory Mucosa ◽  
Locomotor Recovery ◽  
Cord Injury ◽  
Complete Spinal Cord Injury

Object The olfactory mucosa (OM) consists of 2 layers, the epithelium and the lamina propria. Attempts have been made to restore motor function in rat models of spinal cord injury (SCI) by transplanting olfactory ensheathing cells from the lamina propria, but there has been no attempt to transplant the OM in animal models. To investigate the potential of the OM to restore motor function, the authors developed a rat model of SCI and delayed transplantation of syngenic OM. Methods Two weeks after complete transection of the spinal cord at the T-10 level in Wistar rats, pieces of syngenic whole-layer OM were transplanted into the lesion. Rats that underwent respiratory mucosa transplantation were used as controls. The authors evaluated the locomotor activity according to the Basso-Beattie-Bresnahan scale for 8 weeks after transplantation. Obtained spinal cords were analyzed histologically. Results The OM transplantation rats showed significantly greater hindlimb locomotor recovery than the respiratory mucosa–transplanted rats. However, the recovery was limited according to the Basso-Beattie-Bresnahan scale. In the histological examination, the serotonergic raphespinal tract was regenerated. The pseudocyst cavity volume in the vicinity of the SCI lesion correlated negatively with the functional recovery. Conclusions Transplantation of whole-layer OM in rats contributes to functional recovery from SCI, but the effect is limited. In addition to OM transplantation, other means would be necessary for better outcomes in clinical situations.

scholarly journals Is the Recovery of Stepping Following Spinal Cord Injury Mediated by Modifying Existing Neural Pathways or by Generating New Pathways? A Perspective

2001 ◽  
Vol 81 (12) ◽  
pp. 1904-1911 ◽  
Author(s):  
Ray D de Leon ◽  
Roland R Roy ◽  
V Reggie Edgerton
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spinal Injury ◽  
Weight Bearing ◽  
Gait Training ◽  
Neural Pathways ◽  
Neuronal Regeneration ◽  
Locomotor Recovery ◽  
Cord Injury ◽  
Descending Input

Abstract The recovery of stepping ability following a spinal cord injury may be achieved by restoring anatomical connectivity within the spinal cord. However, studies of locomotor recovery in animals with complete spinal cord transection suggest that the adult mammalian spinal cord can acquire the ability to generate stepping after all descending input is eliminated and in the absence of neuronal regeneration. Moreover, rehabilitative gait training has been shown to play a crucial role in teaching existing spinal pathways to generate locomotion and appropriately respond to sensory feedback. This brief review presents evidence that neural networks in the mammalian spinal cord can be modulated pharmacologically and/or with task-specific behavioral training to generate weight-bearing stepping after a spinal injury. Further, the role that spinal learning can play in the management of humans with spinal cord injury is discussed in relation to interventions that are designed primarily to enhance neuronal regeneration.

Combined treatment with αMSH and methylprednisolone fails to improve functional recovery after spinal injury in the rat

2000 ◽  
Vol 859 (2) ◽  
pp. 334-340 ◽  
Author(s):  
Alex J. Lankhorst ◽  
Mariël P. ter Laak ◽  
Frank P.T. Hamers ◽  
Willem Hendrik Gispen
Keyword(s):  
Functional Recovery ◽  
Spinal Injury ◽  
Combined Treatment

scholarly journals Locomotor Training After Human Spinal Cord Injury: A Series of Case Studies

2000 ◽  
Vol 80 (7) ◽  
pp. 688-700 ◽  
Author(s):  
Andrea L Behrman ◽  
Susan J Harkema
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spinal Injury ◽  
Sensory Information ◽  
Locomotor Training ◽  
Overground Walking ◽  
Thoracic Spinal Cord ◽  
Human Spinal Cord ◽  
Thoracic Spinal ◽  
Cord Injury

AbstractMany individuals with spinal cord injury (SCI) do not regain their ability to walk, even though it is a primary goal of rehabilitation. Mammals with thoracic spinal cord transection can relearn to step with their hind limbs on a treadmill when trained with sensory input associated with stepping. If humans have similar neural mechanisms for locomotion, then providing comparable training may promote locomotor recovery after SCI. We used locomotor training designed to provide sensory information associated with locomotion to improve stepping and walking in adults after SCI. Four adults with SCIs, with a mean postinjury time of 6 months, received locomotor training. Based on the American Spinal Injury Association (ASIA) Impairment Scale and neurological classification standards, subject 1 had a T5 injury classified as ASIA A, subject 2 had a T5 injury classified as ASIA C, subject 3 had a C6 injury classified as ASIA D, and subject 4 had a T9 injury classified as ASIA D. All subjects improved their stepping on a treadmill. One subject achieved overground walking, and 2 subjects improved their overground walking. Locomotor training using the response of the human spinal cord to sensory information related to locomotion may improve the potential recovery of walking after SCI.

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