Journal of neurotrauma
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Journal of neurotrauma · Feb 2017
Increased Brain Sensorimotor Network Activation After Incomplete Spinal Cord Injury.
After complete spinal cord injury (SCI), activation during attempted movement of paralyzed limbs is sharply reduced, but after incomplete SCI-the more common form of human injury-it is unknown how attempts to move voluntarily are accompanied by activation of brain motor and sensory networks. Here, we assessed brain activation during ankle movement in subjects with incomplete SCI, among whom voluntary motor function is partially preserved. Adults with incomplete SCI (n = 20) and healthy controls (n = 15) underwent functional magnetic resonance imaging that alternated rest with 0.3-Hz right ankle dorsiflexion. ⋯ Poorer locomotor function correlated with larger activation within several right hemisphere areas, including pre- and post-central gyri, possibly reflecting increased movement complexity and effort, whereas longer time post-SCI was associated with larger activation in left post-central gyrus and bilateral supplementary motor area, which may reflect behaviorally useful adaptations. The results indicate that brain adaptations after incomplete SCI differ sharply from complete SCI, are related to functional behavioral status, and evolve with increasing time post-SCI. The results suggest measures that might be useful for understanding and treating incomplete SCI in human subjects.
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Journal of neurotrauma · Feb 2017
A Morphological and Molecular Characterization of the Spinal Cord Following Ventral Root Avulsion or Distal Peripheral Nerve Axotomy Injuries in Adult Rats.
Retrograde cell death in sensory dorsal root ganglion cells following peripheral nerve injury is well established. However, available data regarding the underlying mechanism behind injury induced motoneuron death are conflicting. By comparing morphological and molecular changes in spinal motoneurons after L4-L5 ventral root avulsion (VRA) and distal peripheral nerve axotomy (PNA) 7 and 14 days postoperatively, we aimed to gain more insight about the mechanism behind injury-induced motoneuron degeneration. ⋯ Moreover, the altered gene expression correlated with protein changes. These results show that the spinal motoneurons reacted in a similar fashion with respect to morphological changes after both proximal and distal injury. However, the increased expression of caspase-3, caspase-8, and related death receptors after VRA suggest that injury- induced motoneuron degeneration is mediated through an apoptotic mechanism, which might involve both the intrinsic and the extrinsic pathways.
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The severe muscle weakness and atrophy measured after human spinal cord injury (SCI) may relate to chronic muscle denervation due to motoneuron death and/or altered muscle use. The aim of this study was to estimate motoneuron death after traumatic human SCI. The diameter and number of myelinated axons were measured in ventral roots post-mortem because ventral roots contain large diameter (> 7 μm) myelinated axons that typically arise from motoneurons and innervate skeletal muscle. ⋯ In seven cases, ventral roots at or below the epicenter had large diameter myelinated axons with unusually thin myelin, a sign of incomplete remyelination. The mean ± SE g ratio (axon diameter/fiber diameter) was 0.60 ± 0.01 for axons of all diameters in five above-lesion ventral roots, but increased significantly for large diameter fibers (≥ 12 μm) in three roots at the lesion epicenter. Motoneuron death after human SCI will coarsen muscle force gradation and control, while extensive muscle denervation will stifle activity-based treatments.
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Journal of neurotrauma · Feb 2017
Clinical Trial Observational StudyCerebrospinal Fluid Biomarkers to Stratify Injury Severity and Predict Outcome in Human Traumatic Spinal Cord Injury.
Neurologic impairment after spinal cord injury (SCI) is currently measured and classified by functional examination. Biological markers that objectively classify injury severity and predict outcome would greatly facilitate efforts to evaluate acute SCI therapies. The purpose of this study was to determine how well inflammatory and structural proteins within the cerebrospinal fluid (CSF) of acute traumatic SCI patients predicted American Spinal Injury Association Impairment Scale (AIS) grade conversion and motor score improvement over 6 months. ⋯ Motor score improvement also was strongly correlated with the 24-h post-injury CSF levels of all six biomarkers. The analysis of CSF can provide valuable biological information about injury severity and recovery potential after acute SCI. Such biological markers may be valuable tools for stratifying individuals in acute clinical trials where variability in spontaneous recovery requires large recruitment cohorts for sufficient power.
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Journal of neurotrauma · Feb 2017
Spinal Cord Transcriptomic and Metabolomic Analysis after Excitotoxic Injection Injury Model of Syringomyelia.
Syringomyelia is a condition of the spinal cord in which a syrinx, or fluid-filled cavity, forms from trauma, malformation, or general disorder. Previous work has shown that in noncanalicular syringomyelia irregular flow and pressure conditions enhance the volumetric growth of syrinxes. A better understanding of the underlying molecular pathways associated with syrinx formation will unveil targets for treatments and possibly prevention of syringomyelia in the future. ⋯ Although transcriptional changes indicated gliosis and loss of neurons, no neuropathic pain was detected by von Frey allodynia testing. Unique transporters were revealed to be highly dysregulated, including significant increases in betaine/glycine transporter (BGT-1), K+/Cl- co-transporter (KCC4), and aquaporin 1 (AQP1), along with the upregulation of small molecule osmolytes taurine and betaine. The identified metabolites are of particular interest because of their involvement in osmotic homeostasis and need to be investigated further for their specific involvement in trauma-induced syrinxes.