Journal of neurotrauma
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Journal of neurotrauma · May 2019
Meta AnalysisProgression of Neuropathic Pain after Acute Spinal Cord Injury: A Meta-Analysis and Framework for Clinical Trials.
The translation of therapeutic interventions to humans with spinal cord injury with the goal of promoting growth and repair in the central nervous system could, inadvertently, drive mechanisms associated with the development of neuropathic pain. A framework is needed to evaluate the probability that a therapeutic intervention for acute spinal cord injury modifies the progression of neuropathic pain. We analyzed a large, longitudinal dataset from the European Multi-Center Study about Spinal Cord Injury (EMSCI) and compared these observations with a previously published Swedish/Danish cohort. ⋯ Characteristics that were significantly associated with the progression of pain included age and sensory and motor preservation. We provide historical benchmarks for estimating the progression of neuropathic pain during the first year after acute SCI. This information will be useful for comparison and evaluating safety during early phase acute spinal cord injury trials.
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Journal of neurotrauma · May 2019
Randomized Controlled TrialSelf-Assisted Standing Enabled by Non-Invasive Spinal Stimulation after Spinal Cord Injury.
Neuromodulation of spinal networks can improve motor control after spinal cord injury (SCI). The objectives of this study were to (1) determine whether individuals with chronic paralysis can stand with the aid of non-invasive electrical spinal stimulation with their knees and hips extended without trainer assistance, and (2) investigate whether postural control can be further improved following repeated sessions of stand training. Using a double-blind, balanced, within-subject cross-over, and sham-controlled study design, 15 individuals with SCI of various severity received transcutaneous electrical spinal stimulation to regain self-assisted standing. ⋯ Quality of balance control was practice-dependent, and improved with subsequent training. During self-initiated body-weight displacements in standing enabled by spinal stimulation, high levels of leg muscle activity emerged, and depended on the amount of muscle loading. Our findings indicate that the lumbosacral spinal networks can be modulated transcutaneously using electrical spinal stimulation to facilitate self-assisted standing after chronic motor and sensory complete paralysis.
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Journal of neurotrauma · May 2019
Clinical TrialFurosemide Unmasks Inhibitory Dysfunction after Spinal Cord Injury in Humans: Implications for Spasticity.
Spasticity after spinal cord injury has considerable quality of life implications, impacts on rehabilitation efforts and necessitates long-term multi-disciplinary pharmacological and non-pharmacological management. The potassium chloride co-transporter (KCC2) plays a central role in intracellular chloride homeostasis and the inhibitory function of mature neurons. Animal studies consistently have demonstrated a downregulation of KCC2 activity after spinal cord transection, causing a shift from the inhibitory action of gamma-aminobutyric acid and glycine to an excitatory effect. ⋯ The lack of furosemide effect after spinal cord injury suggests KCC2 dysfunction in humans, resulting in reduced inhibitory synaptic transmission in spinal neurons. Our findings suggest that KCC2 dysfunction may be an important etiological factor in hyperreflexia after spinal cord injury. These observations may pave the way to novel therapeutic strategies against spasticity centered on chloride homeostasis.
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Journal of neurotrauma · May 2019
Longitudinal In Vivo Diffusion Magnetic Resonance Imaging Remote from the Lesion Site in Rat Spinal Cord Injury.
Diffusion tensor imaging (DTI) has demonstrated success as a biomarker of spinal cord injury (SCI) severity as shown from numerous pre-clinical studies. However, artifacts from stabilization hardware at the lesion have precluded its use for longitudinal assessments. Previous research has documented ex vivo diffusion changes in the spinal cord both caudal and cranial to the injury epicenter. ⋯ At 90 days, axial diffusivity (ADFWE), mean diffusivity (MDFWE), and free water fraction (FWFFWE) using the FWE model were found to be significantly correlated with BBB score. FWE was found to be more predictive of injury severity than conventional DTI, specifically at later time-points. This study validated the use of FWE technique in spinal cord and demonstrated its sensitivity to injury remotely.
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Journal of neurotrauma · May 2019
Multi-Potent Adult Progenitor Cells, but not Tissue Inhibitor of Matrix Metalloproteinase-3, Increase Tissue Sparing and Reduce Urological Complications following Spinal Cord Injury.
Following spinal cord injury (SCI), inflammation amplifies damage beyond the initial insult, providing an opportunity for targeted treatments. An ideal protective therapy would reduce both edema within the lesion area and the activation/infiltration of detrimental immune cells. Previous investigations demonstrated the efficacy of intravenous injection of multipotent adult progenitor cells (MAPC®) to modulate immune response following SCI, leading to significant improvements in tissue sparing, locomotor and urological functions. ⋯ The results suggest that intravenous delivery of MAPC cell therapy 1 day following acute SCI significantly improves tissue sparing and impacts functional recovery. TIMP3 treatment provided no significant benefit, and further, when co-administered with MAPC cells, it abrogated the therapeutic effects of MAPC cell therapy. Importantly, this study demonstrated for the first time that acute treatment of SCI with MAPC cells can significantly reduce the incidence of urinary tract infection (UTI) and the use of antibiotics for UTI treatment.