Hindlimb stepping movements in complete spinal rats induced by epidural spinal cord stimulation

Ichiyama, Ronaldo M.; Gerasimenko, Yu. P.; Zhong, Hui; Roy, Roland R.; Edgerton, V. Reggie

doi:10.1016/j.neulet.2005.04.049

Cited by 218 publications

(241 citation statements)

References 23 publications

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“…However, when the animal's limbs are placed on a moving treadmill belt they will begin stepping at a rate and with kinematics features appropriate for the speed of the belt. A similar effect of the motor responses to sensory input can be routinely observed during tonic epidural stimulation in a complete spinal cat or rat Ichiyama et al, 2005).…”

Section: Modulation Of the Physiological State And Afferent Control Osupporting

confidence: 59%

“…Examples of a more prolonged modulation of state dependence have been demonstrated using pharmacological agonists and antagonists of selected neurotransmitter systems known to be important in the generation of locomotion (Rossignol and Barbeau, 1993). We also have demonstrated that the state dependence of the spinal circuitry can be modulated by epidural electrical stimulation of the dorsum of the lumbosacral spinal cord of the adult spinal rat, i.e., epidural stimulation at specific segments of the spinal cord can elicit and/or enable reflex and locomotor-like activity in rats having a complete spinal cord transection at a mid-thoracic level Ichiyama et al, 2005;Lavrov et al, 2006). Essentially, the early experiments of Shik and colleagues (1966) demonstrated that tonic stimulation of the mesencephalic locomotor region modulates the state dependence of the spinal cord in the sense that the gait and speed of stepping at a given treadmill speed was dependent on the intensity of the stimulation.…”

Section: Modulation Of the Physiological State And Afferent Control Omentioning

confidence: 78%

“…Tonically stimulating the dorsal surface of the lumbosacral spinal cord via electrodes placed on top of the dura can induce locomotor-like movements in vivo in complete spinal rats (Ichiyama, 2005) and cats Gerasimenko et al, 2003) and in humans that are classified as clinically complete (Dimitrijevic et al, 1998). The intensity, frequency, and site of simulation are important parameters to control in defining the nature of the locomotor movements that are generated.…”

Section: Epidural Stimulationmentioning

confidence: 99%

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Training locomotor networks

Edgerton

Courtine

Gerasimenko

et al. 2008

Brain Research Reviews

269

201

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For a complete adult spinal rat to regain some weight-bearing stepping capability, it appears that a sequence of specific proprioceptive inputs that are similar, but not identical, from step to step must be generated over repetitive step cycles. Furthermore, these cycles must include the activation of specific neural circuits that are intrinsic to the lumbosacral spinal cord segments. For these sensorimotor pathways to be effective in generating stepping, the spinal circuitry must be modulated to an appropriate excitability level. This level of modulation is sustained from supraspinal input in intact, but not spinal, rats. In a series of experiments with complete spinal rats, we have shown that an appropriate level of excitability of the spinal circuitry can be achieved using widely different means. For example, this modulation level can be acquired pharmacologically, via epidural electrical stimulation over specific lumbosacral spinal cord segments, and/or by use-dependent mechanisms such as step or stand training. Evidence as to how each of these treatments can "tune" the spinal circuitry to a "physiological state" that enables it to respond appropriately to proprioceptive input will be presented. We have found that each of these interventions can enable the proprioceptive input to actually control extensive details that define the dynamics of stepping over a range of speeds, loads, and directions. A series of experiments will be described that illustrate sensory control of stepping and standing after a spinal cord injury and the necessity for the "physiological state" of the spinal circuitry to be modulated within a critical window of excitability for this control to be manifested. The present findings have important consequences not only for our understanding of how the motor pattern for stepping is formed, but also for the design of rehabilitation intervention to restore lumbosacral circuit function in humans following a spinal cord injury.

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Section: Modulation Of the Physiological State And Afferent Control Osupporting

confidence: 59%

Section: Modulation Of the Physiological State And Afferent Control Omentioning

confidence: 78%

Section: Epidural Stimulationmentioning

confidence: 99%

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Training locomotor networks

Edgerton

Courtine

Gerasimenko

et al. 2008

Brain Research Reviews

269

201

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“…In an analogous manner, spinal-cord NPs might utilize the topographical organization of spinal axons into bundles (i.e., white matter tracts) to recruit specific motor outputs via surface stimulation. The relevance of this approach has been supported by studies in which spinal cord surface stimulation has been used effectively to elicit coordinated motor responses -including locomotion-in both rats and humans (Gerasimenko et al, 2006;Ichiyama et al, 2005;Magnuson et al, 1995;Magnuson and Trinder, 1997).…”

Section: Introductionmentioning

confidence: 99%

A lithographically-patterned, elastic multi-electrode array for surface stimulation of the spinal cord

Meacham

Giuly

Guo

et al. 2007

Biomed Microdevices

101

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A new, scalable process for microfabrication of a silicone-based, elastic multi-electrode array (MEA) is presented. The device is constructed by spinning poly(dimethylsiloxane) (PDMS) silicone elastomer onto a glass slide, depositing and patterning gold to construct wires and electrodes, spinning on a second PDMS layer, and then micropatterning the second PDMS layer to expose electrode contacts. The micropatterning of PDMS involves a custom reactive ion etch (RIE) process that preserves the underlying gold thin film. Once completed, the device can be removed from the glass slide for conformal interfacing with neural tissue. Prototype MEAs feature electrodes smaller than those known to be reported on silicone substrate (60 μm diameter exposed electrode area) and were capable of selectively stimulating the surface of the in vitro isolated spinal cord of the juvenile rat. Stretchable serpentine traces were also incorporated into the functional PDMS-based MEA, and their implementation and testing is described.

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“…Lumbar spinal cord segments are an active area of SCI research, including recent studies investigating therapeutic and curative epidural stimulation in both the rat and the human. [38][39][40][41] In addition to epidural stimulation, treadmill and other rehabilitative therapies have harnessed the intrinsic lumbar spinal cord circuitry after injury to a higher spinal level (cervical or thoracic). 42,43 It would be of interest to examine these techniques in using spared gray/white matter after lumbar SCI to determine efficacy when the lumbar circuitry is the site of injury.…”

Section: Neurobehavioral Recoverymentioning

confidence: 99%

A New Acute Impact-Compression Lumbar Spinal Cord Injury Model in the Rodent

Moonen

Satkunendrarajah

Wilcox

et al. 2016

Journal of Neurotrauma

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Traumatic injury to the lumbar spinal cord results in complex central and peripheral nervous tissue damage causing significant neurobehavioral deficits and personal/social adversity. Although lumbar cord injuries are common in humans, there are few clinically relevant models of lumbar spinal cord injury (SCI). This article describes a novel lumbar SCI model in the rat. The effects of moderate (20 g), moderate-to-severe (26 g) and severe (35 g, and 56 g) clip impactcompression injuries at the lumbar spinal cord level L1-L2 (vertebral level T11-T12) were assessed using several neurobehavioral, neuroanatomical, and electrophysiological outcome measures. Lesions were generated after meticulous anatomical landmarking using microCT, followed by laminectomy and extradural inclusion of central and radicular elements to generate a traumatic SCI. Clinically relevant outcomes, such as MR and ultrasound imaging, were paired with robust morphometry. Analysis of the lesional tissue demonstrated that pronounced tissue loss and cavitation occur throughout the acute to chronic phases of injury. Behavioral testing revealed significant deficits in locomotion, with no evidence of hindlimb weight-bearing or hindlimb-forelimb coordination in any injured group. Evaluation of sensory outcomes revealed highly pathological alterations including mechanical allodynia and thermal hyperalgesia indicated by increasing avoidance responses and decreasing latency in the tail-flick test. Deficits in spinal tracts were confirmed by electrophysiology showing increased latency and decreased amplitude of both sensory and motor evoked potentials (SEP/MEP), and increased plantar H-reflex indicating an increase in motor neuron excitability. This is a comprehensive lumbar SCI model and should be useful for evaluation of translationally oriented pre-clinical therapies.

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Hindlimb stepping movements in complete spinal rats induced by epidural spinal cord stimulation

Cited by 218 publications

References 23 publications

Training locomotor networks

Training locomotor networks

A lithographically-patterned, elastic multi-electrode array for surface stimulation of the spinal cord

A New Acute Impact-Compression Lumbar Spinal Cord Injury Model in the Rodent

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