Spinal cord reflexes induced by epidural spinal cord stimulation in normal awake rats

Gerasimenko, Yury; Lavrov, Igor; Courtine, Grégoire; Ichiyama, Ronaldo M.; Dy, Christine J.; Zhong, Hui; Roy, Roland R.; Edgerton, V. Reggie

doi:10.1016/j.jneumeth.2006.05.004

Cited by 132 publications

(142 citation statements)

References 42 publications

(43 reference statements)

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“…Some progress, however, has been made by examining the amplitudes and latencies of potentials simultaneously evoked in multiple muscles by single pulses of ES in both laboratory animals and human subjects. Both monosynaptic and polysynaptic responses are modulated in a phase-dependent manner during treadmill locomotion in normal rats (Gerasimenko et al, 2006a). A similar phenomenon has been observed in uninjured humans subjects when stimulating the spinal cord transcutaneously (Courtine et al, 2007).…”

Section: Which Axons and Neurons Are Being Activated By Es?supporting

confidence: 53%

Epidural stimulation: Comparison of the spinal circuits that generate and control locomotion in rats, cats and humans

Gerasimenko

Roy

Edgerton

2008

Experimental Neurology

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159

107

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Although epidural stimulation is a technique that has been used for a number of years to treat individuals with a spinal cord injury, the intended outcome has been to suppress plasticity and pain. Over the last decade considerable progress has been made in realizing the potential of epidural stimulation to facilitate posture and locomotion in subjects with severe spinal cord injury who lack the ability to stand or to step. This progress has resulted primarily from experiments with mice, rats and cats having a complete spinal cord transection at a mid-thoracic level and in humans with a complete spinal cord injury. This review describes some of these experiments performed after the complete elimination of supraspinal input that demonstrate that the circuitry necessary to control remarkably normal locomotion appears to reside within the lumbosacral region of the spinal cord. These experiments, however, also demonstrate the essential role of processing proprioceptive information associated with weight-bearing stepping or standing by the spinal circuitry. For example, relatively simple tonic signals provided to the dorsum of the spinal cord epidurally can result in complex and highly adaptive locomotor patterns. Experiments emphasizing a significant complementary effect of epidural stimulation when combined with pharmacological facilitation, e.g., serotonergic agonists, and/or chronic step training also are described. Finally, a major point emphasized in this review is the striking similarity of the lumbosacral circuitry controlling locomotion in the rat and in the human.

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Section: Which Axons and Neurons Are Being Activated By Es?supporting

confidence: 53%

Epidural stimulation: Comparison of the spinal circuits that generate and control locomotion in rats, cats and humans

Gerasimenko

Roy

Edgerton

2008

Experimental Neurology

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159

107

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“…The contraction is a reflex response to stimulation of dorsal column fibers, i.e., primary afferents. Activation of these afferent fibers potentially could excite the motoneuronal pools that innervate muscles in the lower limbs (Gerasimenko et al, 2006). The experimental SCS (50 Hz; 0.2 ms, monophasic rectangular pulses), is performed at 30%, 60%, 90%, 300% or 10 times of MT .…”

Section: 12mentioning

confidence: 99%

Putative mechanisms behind effects of spinal cord stimulation on vascular diseases: A review of experimental studies

Linderoth

Foreman

2008

Autonomic Neuroscience

152

106

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Spinal cord stimulation (SCS) is a widely used clinical technique to treat ischemic pain in peripheral, cardiac and cerebral vascular diseases. The use of this treatment advanced rapidly during the late 80's and 90's, particularly in Europe. Although the clinical benefits of SCS are clear and the success rate remains high, the mechanisms are not yet completely understood. SCS at lumbar spinal segments (L2-L3) produces vasodilation in the lower limbs and feet which is mediated by antidromic activation of sensory fibers and decreased sympathetic outflow. SCS at thoracic spinal segments (T1-T2) induces several benefits including pain relief, reduction in both frequency and severity of angina attacks, and reduced short-acting nitrate intake. The benefits to the heart are not likely due to an increase, or redistribution of local blood flow, rather, they are associated with SCS-induced myocardial protection and normalization of the intrinsic cardiac nervous system. At somewhat lower cervical levels (C3-C6), SCS induces increased blood flow in the upper extremities. SCS at the upper cervical spinal segments (C1-C2) increased cerebral blood flow, which is associated with a decrease in sympathetic activity, an increase in vasomotor center activity and a release of neurohumoral factors. This review will summarize the basic science studies that have contributed to our understanding about mechanisms through which SCS produces beneficial effects when used in the treatment of vascular diseases. Furthermore, this review will particularly focus on the antidromic mechanisms of SCS-induced vasodilation in the lower limbs and feet.

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“…Although this phenomenon has been investigated extensively, the specific spinal networks responsible for generating locomotion cannot be completely described by classical models (Graham-Brown, 1911;Engberg and Lundberg, 1969;Smith et al, 1998;Burke et al, 2001;Lafreniere-Roula and McCrea, 2005;Ivanenko et al, 2006;Rybak et al, 2006a,b). Recent studies of locomotion facilitated by epidural stimulation have provided some new perspectives on how specific locomotor networks in rats, cats, and humans function in vivo (Dimitrijevic et al, 1998;Dimitrijevic and Dimitrijevic, 2002;Gerasimenko et al, 2003Gerasimenko et al, , 2006Gerasimenko et al, , 2007.…”

Section: Introductionmentioning

confidence: 99%

Epidural Stimulation Induced Modulation of Spinal Locomotor Networks in Adult Spinal Rats

Lavrov

Fong

et al. 2008

Journal of Neuroscience

138

122

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The importance of the in vivo dynamic nature of the circuitries within the spinal cord that generate locomotion is becoming increasingly evident. We examined the characteristics of hindlimb EMG activity evoked in response to epidural stimulation at the S1 spinal cord segment in complete midthoracic spinal cord-transected rats at different stages of postlesion recovery. A progressive and phasedependent modulation of monosynaptic (middle) and long-latency (late) stimulation-evoked EMG responses was observed throughout the step cycle. During the first 3 weeks after injury, the amplitude of the middle response was potentiated during the EMG bursts, whereas after 4 weeks, both the middle and late responses were phase-dependently modulated. The middle-and late-response magnitudes were closely linked to the amplitude and duration of the EMG bursts during locomotion facilitated by epidural stimulation. The optimum stimulation frequency that maintained consistent activity of the long-latency responses ranged from 40 to 60 Hz, whereas the shortlatency responses were consistent from 5 to 130 Hz. These data demonstrate that both middle and late evoked potentials within a motor pool are strictly gated during in vivo bipedal stepping as a function of the general excitability of the motor pool and, thus, as a function of the phase of the step cycle. These data demonstrate that spinal cord epidural stimulation can facilitate locomotion in a time-dependent manner after lesion. The long-latency responses to epidural stimulation are correlated with the recovery of weight-bearing bipedal locomotion and may reflect activation of interneuronal central pattern-generating circuits.

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Spinal cord reflexes induced by epidural spinal cord stimulation in normal awake rats

Cited by 132 publications

References 42 publications

Epidural stimulation: Comparison of the spinal circuits that generate and control locomotion in rats, cats and humans

Epidural stimulation: Comparison of the spinal circuits that generate and control locomotion in rats, cats and humans

Putative mechanisms behind effects of spinal cord stimulation on vascular diseases: A review of experimental studies

Epidural Stimulation Induced Modulation of Spinal Locomotor Networks in Adult Spinal Rats

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