Maladaptive spinal plasticity opposes spinal learning and recovery in spinal cord injury (original) (raw)
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Plasticity of the Spinal Neural Circuitry After Injury*
Annual Review of Neuroscience, 2004
Motor function is severely disrupted following spinal cord injury (SCI). The spinal circuitry, however, exhibits a great degree of automaticity and plasticity after an injury. Automaticity implies that the spinal circuits have some capacity to perform complex motor tasks following the disruption of supraspinal input, and evidence for plasticity suggests that biochemical changes at the cellular level in the spinal cord can be induced in an activity-dependent manner that correlates with sensorimotor recovery. These characteristics should be strongly considered as advantageous in developing therapeutic strategies to assist in the recovery of locomotor function following SCI. Rehabilitative efforts combining locomotor training pharmacological means and/or spinal cord electrical stimulation paradigms will most likely result in more effective methods of recovery than using only one intervention. * Abbreviations: 5-hydroxytryptamine (5-HT); 2-amino-5-phosphonovaleric acid (AP-5); American Spinal Injury Association (ASIA); brain-derived neurotrophic factor (BDNF); central nervous system (CNS); central pattern generation (CPG); electrical stimulation (ES); electromyography (EMG); extensor digitorum longus (EDL); gamma-aminobutyric acid (GABA); glial fibrillary acidic protein (GFAP); glutamic acid decarboxylase (GAD); long-term potentiation (LTP); long-term depression (LTD); m-chlorophenylpiperazine (m-CPP); medial gastrocnemius (MG); neurotrophin-3 (NT-3); noradrenaline (NA); N-methyl-D-aspartate (NMDA); paw contact (PC); peripheral nervous system (PNS); soleus (SOL); spinal cord injury (SCI); swing-phase force field (SWPFF); tibialis anterior (TA).
Pathway-specific plasticity in the human spinal cord
European Journal of Neuroscience, 2012
The aim of the present study was to artificially induce plasticity in the human spinal cord and evaluate whether this plasticity is pathway specific. For this purpose, a technique called paired associative stimulation (PAS) was applied. Volleys evoked by transcranial magnetic stimulation over the primary motor cortex and peripheral nerve stimulation of the nervus tibialis in the popliteal fossa were timed to coincide at the spinal level. The transmission of different corticospinal projections was assessed before and after PAS using conditioned H-reflexes. Different groups of healthy volunteers (28 ± 5 years) were tested; intervention groups 1 (n = 9) and 2 (n = 8) received spinal PAS (360 paired stimuli) and the induced effects were evaluated using cortical (group 1) or cervicomedullary (group 2) conditioning of musculus soleus H-reflexes. After spinal PAS, the conditioned H-reflexes were significantly facilitated when tested with cortical and cervicomedullary stimulation. The effect of the latter technique is independent of changes in the excitability of cortical neurons. Therefore, the finding that conditioned H-reflexes were increased after spinal PAS when tested with both cortical and cervicomedullary stimulation suggests that neural plasticity was induced within the spinal cord. The facilitation could only be observed for specific inter-stimulus intervals between volleys induced by peripheral nerve stimulation and transcranial magnetic stimulation. As the specific inter-stimulus intervals were assumed to relate to transmission within specific motor pathways, it is argued that changes in the corticospinal transmission were pathway-specific. These findings may be helpful in inducing and assessing neural plasticity in pathological conditions like spinal cord injuries.
Activity-dependent plasticity in spinal cord injury
The Journal of Rehabilitation Research and Development, 2008
The adult mammalian central nervous system (CNS) is capable of considerable plasticity, both in health and disease. After spinal neurotrauma, the degrees and extent of neuroplasticity and recovery depend on multiple factors, including the level and extent of injury, postinjury medical and surgical care, and rehabilitative interventions. Rehabilitation strategies focus less on repairing lost connections and more on influencing CNS plasticity for regaining function. Current evidence indicates that strategies for rehabilitation, including passive exercise, active exercise with some voluntary control, and use of neuroprostheses, can enhance sensorimotor recovery after spinal cord injury (SCI) by promoting adaptive structural and functional plasticity while mitigating maladaptive changes at multiple levels of the neuraxis. In this review, we will discuss CNS plasticity that occurs both spontaneously after SCI and in response to rehabilitative therapies.
Frontiers in physiology, 2012
The spinal cord demonstrates several forms of plasticity that resemble brain-dependent learning and memory. Among the most studied form of spinal plasticity is spinal memory for noxious (nociceptive) stimulation. Numerous papers have described central pain as a spinally-stored memory that enhances future responses to cutaneous stimulation. This phenomenon, known as central sensitization, has broad relevance to a range of pathological conditions. Work from the spinal cord injury (SCI) field indicates that the lumbar spinal cord demonstrates several other forms of plasticity, including formal learning and memory. After complete thoracic SCI, the lumbar spinal cord can be trained by delivering stimulation to the hindleg when the leg is extended. In the presence of this response-contingent stimulation the spinal cord rapidly learns to hold the leg in a flexed position, a centrally mediated effect that meets the formal criteria for instrumental (response-outcome) learning. Instrumental f...
Plasticity in Sublesionally Located Neurons Following Spinal Cord Injury
Journal of Neurophysiology, 2007
YH. Suppression by intrathecal BmK IT2 on rat spontaneous pain behaviors and spinal c-Fos expression induced by formalin. Brain Res Bull 73: 248 -253, 2007. Ballermann M, Fouad K. Spontaneous locomotor recovery in spinal cord injured rats is accompanied by anatomical plasticity of reticulospinal fibers. S. Noradrenergic agonists and locomotor training affect locomotor recovery after cord transection in adult cats. Brain Res Bull 30: 387-393, 1993. Barbeau H, Rossignol S. Recovery of locomotion after chronic spinalization in the adult cat. Brain Res 412: 84 -95, 1987. Bareyre FM, Kerschensteiner M, Raineteau O, Mettenleiter TC, Weinmann O, Schwab ME. The injured spinal cord spontaneously forms a new intraspinal circuit in adult rats. Nat Neurosci 7: 269 -277, 2004. Invited Review 2499 SUBLESIONAL PLASTICITY AFTER SCI J Neurophysiol • VOL 98 • NOVEMBER 2007 • www.jn.org
Spinal cord injury and plasticity: Opportunities and challenges
Brain Research Bulletin, 2011
There is still no effective treatment to promote functional recovery following spinal cord injury. However, promoting injury-induced adaptive changes (plasticity) within the central nervous system, associated with repair, promise new treatment strategies. Recent contributions from our group and current challenges of this relatively young field are discussed in this review.
Targeted-Plasticity in the Corticospinal Tract After Human Spinal Cord Injury
Spinal cord injury (SCI) often results in impaired or absent sensorimotor function below the level of the lesion. Recent electro-physiological studies in humans with chronic incomplete SCI demonstrate that voluntary motor output can be to some extent potentiated by noninvasive stimulation that targets the corticospinal tract. We discuss emerging approaches that use transcranial magnetic stimulation (TMS) over the primary motor cortex and electrical stimulation over a peripheral nerve as tools to induce plasticity in residual corticospinal projections. A single TMS pulse over the primary motor cortex has been paired with peripheral nerve electrical stimulation at precise interstimulus intervals to reinforce corticospinal synaptic transmission using principles of spike-timing dependent plasticity. Pairs of TMS pulses have also been used at interstimulus intervals that mimic the periodicity of descending indirect (I) waves volleys in the corticospinal tract. This data, along with information about the extent of the injury, provides a new framework for exploring the contribution of the corticospinal tract to recovery of function following SCI.
Journal of neurotrauma, 2016
Spinal cord injury (SCI) is often accompanied by other tissue damage (polytrauma) that provides a source of pain (nociceptive) input. Recent findings are reviewed that show SCI places the caudal tissue in a vulnerable state that exaggerates the effects nociceptive stimuli and promotes the development of nociceptive sensitization. Stimulation that is both unpredictable and uncontrollable induces a form of maladaptive plasticity that enhances nociceptive sensitization and impairs spinally mediated learning. In contrast, relational learning induces a form of adaptive plasticity that counters these adverse effects. SCI sets the stage for nociceptive sensitization by disrupting serotonergic (5HT) fibers that quell overexcitation. The loss of 5HT can enhance neural excitability by reducing membrane-bound K(+)-Cl(-) cotransporter 2, a cotransporter that regulates the outward flow of Cl(-). This increases the intracellular concentration of Cl(-), which reduces the hyperpolarizing (inhibitor...
Frontiers in Neural Circuits, 2014
Research has shown that spinal circuits have the capacity to adapt in response to training, nociceptive stimulation and peripheral inflammation. These changes in neural function are mediated by physiological and neurochemical systems analogous to those that support plasticity within the hippocampus (e.g., long-term potentiation and the NMDA receptor). As observed in the hippocampus, engaging spinal circuits can have a lasting impact on plastic potential, enabling or inhibiting the capacity to learn. These effects are related to the concept of metaplasticity. Behavioral paradigms are described that induce metaplastic effects within the spinal cord. Uncontrollable/unpredictable stimulation, and peripheral inflammation, induce a form of maladaptive plasticity that inhibits spinal learning. Conversely, exposure to controllable or predictable stimulation engages a form of adaptive plasticity that counters these maladaptive effects and enables learning. Adaptive plasticity is tied to an up-regulation of brain derived neurotrophic factor (BDNF). Maladaptive plasticity is linked to processes that involve kappa opioids, the metabotropic glutamate (mGlu) receptor, glia, and the cytokine tumor necrosis factor (TNF). Uncontrollable nociceptive stimulation also impairs recovery after a spinal contusion injury and fosters the development of pain (allodynia). These adverse effects are related to an up-regulation of TNF and a down-regulation of BDNF and its receptor (TrkB). In the absence of injury, brain systems quell the sensitization of spinal circuits through descending serotonergic fibers and the serotonin 1A (5HT 1A) receptor. This protective effect is blocked by surgical anesthesia. Disconnected from the brain, intracellular Cl − concentrations increase (due to a downregulation of the cotransporter KCC2), which causes GABA to have an excitatory effect. It is suggested that BDNF has a restorative effect because it up-regulates KCC2 and re-establishes GABA-mediated inhibition.