Journal of neurotrauma
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Journal of neurotrauma · Mar 2019
Circulating microRNAs, Vascular Risk, and Physical Activity in Spinal Cord-Injured Subjects.
The aim of this study was to compare the expression of serum microRNAs (miRNAs) in individuals with spinal cord injury (SCI) (athletes [SCI-A] and sedentary [SCI-S]) and able-bodied (AB) individuals, and investigate the relationship of miRNAs with carotid intima-media thickness (cIMT) and serum oxidized LDL-cholesterol (oxLDL) among SCI subjects. Seventeen SCI-S, 23 SCI-A, and 22 AB males were evaluated by clinical and laboratory analysis, and had oxLDL and cIMT measured by enzyme-linked immunosorbent assay (ELISA) and ultrasonography, respectively. A total of 754 miRNAs were measured using a TaqMan OpenArray® Human MicroRNA system. ⋯ Gene set enrichment analysis demonstrated that miRNAs related to cIMT and oxLDL may be involved in molecular pathways regulating vascular function and remodeling. In conclusion, this exploratory analysis suggests that variations in circulating miRNA expression in individuals with SCI compared with AB subjects are markedly attenuated by regular physical activity. Several miRNAs may be involved in physical activity-related improvements in vascular risk and remodeling among SCI individuals.
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Journal of neurotrauma · Mar 2019
Randomized Controlled Trial Multicenter StudyClinical Outcomes from a Multi-Center Study of Human Neural Stem Cell Transplantation in Chronic Cervical Spinal Cord Injury.
Human neural stem cell transplantation (HuCNS-SC®) is a promising central nervous system (CNS) tissue repair strategy in patients with stable neurological deficits from chronic spinal cord injury (SCI). These immature human neural cells have been demonstrated to survive when transplanted in vivo, extend neural processes, form synaptic contacts, and improve functional outcomes after experimental SCI. A phase II single blind, randomized proof-of-concept study of the safety and efficacy of HuCNS-SC transplantation into the cervical spinal cord was undertaken in patients with chronic C5-7 tetraplegia, 4-24 months post-injury. ⋯ At 1 year post-transplantation, there was no evidence of additional spinal cord damage, new lesions, or syrinx formation on magnetic resonance (MR) imaging. In summary, the incremental dose escalation design established surgical safety, tolerability, and feasibility in Cohort I. Interim analysis of Cohorts I and II demonstrated a trend toward Upper Extremity Motor Score (UEMS) and Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) motor gains in the treated participants, but at a magnitude below the required clinical efficacy threshold set by the sponsor to support further development resulting in early study termination.
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Journal of neurotrauma · Mar 2019
Activating Adiponectin Signaling with Exogenous AdipoRon Reduces Myelin Lipid Accumulation and Suppresses Macrophage Recruitment after Spinal Cord Injury.
Myelin-laden macrophages (mye-MΦ), resulting primarily from internalization of myelin debris by infiltrating bone marrow-derived macrophages in spinal cord injury (SCI), trigger inflammatory responses that largely contribute to secondary injury. Adiponectin, which is secreted from adipose tissue, is an important hormone that modulates macrophage inflammation. In the present study, we examined the role of adiponectin on macrophage-mediated neuroinflammation after SCI. ⋯ In vivo data further confirmed that intravenous administration of AdipoRon after SCI dampened recruitment of macrophages and reduced myelin lipid accumulation. Accordingly, AdipoRon treatment ameliorated post-SCI tissue damage and astrogliosis, resulting in improved motor function. Although there was no significant pathological exacerbation in adiponectin-null mice subjected to SCI, our work reveals a functional link between adiponectin and hematogenous macrophages in the context of SCI, suggesting that activation of adiponectin signaling is a promising therapeutic approach to mitigate mye-MΦ-mediated neuroinflammation in neurological disorders involving demyelination.
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Journal of neurotrauma · Mar 2019
Submaximal Marker for Investigating Peak Muscle Torque Using Neuromuscular Electrical Stimulation after Paralysis.
Spinal cord injury (SCI) results in deleterious skeletal muscle adaptations, such as relevant atrophy and loss of force. In particular, the relevant loss of lower-limb force-generating capacity may limit functional mobility even if neuronal control was sufficient. Currently, methods of assessing maximal force-generating capacity using neuromuscular electrical stimulation (NMES) are limited in individuals who cannot tolerate higher stimulation amplitudes, such as those with residual sensation and those at risk of fracture. ⋯ NMES was delivered starting with an amplitude of 5 mA, and increasing by 5 mA for every subsequent stimulation until either the participant requested to stop the stimulation or the maximum stimulation amplitude (140 mA) was reached. Significant correlations between peak slope of the recruitment curve and peak torque for all muscle groups were found (knee extensors, r = 0.75; p < 0.0001; knee flexors, r = 0.68; p < 0.0001; ankle plantarflexors, r = 0.91; p < 0.0001), indicating that muscles that show greater peak slope of the recruitment curve tend to generate a greater peak torque. This suggests that peak slope, which was achieved at an average stimulation intensity (55.0 mA) that was 43% smaller than that corresponding to peak torque (97.4 mA), may be used as a submaximal marker for characterizing maximal torque output in individuals with SCI.
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Journal of neurotrauma · Mar 2019
Diffusion Tensor Imaging Assessment of Regional White Matter Changes in the Cervical and Thoracic Spinal Cord in Pediatric Subjects.
There are no studies to date,describing changes in the diffusion tensor imaging (DTI) metrics of the white matter (WM) regions of the entire cervical and thoracic spinal cord (SC) remote from the lesion in pediatric spinal cord injury (SCI) subjects. The purpose of this study was to determine whether DTI at sites cephalad and caudal to a lesion provides measures of cord abnormalities in children with chronic SCI. A retrospective study included 10 typically developing subjects (TD) and 10 subjects with chronic SCI who underwent SC imaging in 2014-2017. ⋯ In motor tracts cephalad to the lesion, FA was significantly decreased whereas AD was significantly increased in the proximal segment; however, AD was decreased in the distal and middle segments. International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) total score was significantly correlated with FA and AD of the motor and sensory tracts cephalad to the lesion. This study demonstrates that FA and AD have the potential to be sensitive biomarkers of the full extent of cord injury and might be useful in detecting remote injuries to the SC and in guiding new treatments.