Journal of neurotrauma
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Journal of neurotrauma · Feb 2017
Predicting recruitment feasibility for acute spinal cord injury clinical trials in Canada using national registry data.
Traumatic spinal cord injury (SCI) represents a significant burden of illness, but it is relatively uncommon and heterogeneous, making it challenging to achieve sufficient subject enrollment in clinical trials of therapeutic interventions for acute SCI. The Rick Hansen Spinal Cord Injury Registry (RHSCIR) is a national SCI Registry that enters patients with SCI from acute-care centers across Canada. To predict the feasibility of conducting clinical trials of acute SCI within Canada, we have applied the inclusion/exclusion criteria of six previously conducted SCI trials to the RHSCIR data set and generated estimates of how many Canadian persons would have been eligible theoretically for enrollment in these studies. ⋯ Projected annual numbers of eligible patients for each trial were: Minocycline, 117; Riluzole, 62; STASCIS, 109; Cethrin, 101; NOGO, 82; and Sygen, 70. An additional 8.0% of the sample had a major head injury (Glasgow Coma Scale [GCS] score ≤12) and would have been excluded from the trials. RHSCIR provides a comprehensive national data set that may serve as a useful tool in the planning of multicenter clinical SCI trials.
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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
Temporal and Spatial Evolution of Raised Intraspinal Pressure Following Traumatic Spinal Cord Injury.
Traumatic spinal cord injury (SCI) often leads to permanent neurological impairment. Currently, the only clinically effective intervention for patients with acute SCI is surgical decompression by removal of impinging bone fragments within 24 h after injury. Recent clinical studies suggest that elevated intraparenchymal spinal pressure (ISP) limits functional recovery following SCI. ⋯ Interestingly, the contribution of the dural and pial compartments toward increased ISP changes with time after injury: Dural and pial linings contribute almost equally to increased ISP during the acute phase, whereas the dural lining is primarily responsible for elevated ISP during the subacute phase (78.9%). Our findings suggest that a rat contusion SCI model in combination with novel micro-catheters allows for direct measurement of ISP after SCI. Similarly to traumatic brain injury, raised tissue pressure is likely to have detrimental effects on spontaneous recovery following SCI.
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Opioids and non-steroidal anti-inflammatory drugs are used commonly to manage pain in the early phase of spinal cord injury (SCI). Despite its analgesic efficacy, however, our studies suggest that intrathecal morphine undermines locomotor recovery and increases lesion size in a rodent model of SCI. Similarly, intravenous (IV) morphine attenuates locomotor recovery. ⋯ These data suggest that morphine use is contraindicated in the acute phase of a spinal injury. Faced with a lifetime of intractable pain, however, simply removing any effective analgesic for the management of SCI pain is not an ideal option. Instead, these data underscore the critical need for further understanding of the molecular pathways engaged by conventional medications within the pathophysiological context of an injury.
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Journal of neurotrauma · Feb 2017
High thoracic contusion model for the investigation of cardiovascular function post spinal cord injury.
Cardiovascular disease is the leading cause of death for individuals with spinal cord injury (SCI). Because of a lack of a standardized and accessible animal model for cardiovascular disease after SCI, few laboratories have conducted pre-clinical trials aimed at reinstating descending cardiovascular control. Here, we utilized common contusion methodology applied to the midline of the upper-thoracic cord of adult Wistar rats accompanied with telemetric blood pressure monitoring and FluoroGold retrograde neuronal tracing, as well as lesion site and lumbrosacral afferent immunohistochemistry. ⋯ Further, we provide a description of the neuroanatomical changes that accompany cardiovascular abnormalities. Specifically, we describe 1) the injury site including white matter sparing as well as lesion volume, and their correlations to cardiovascular as well as motor outcomes; 2) the severity of injury-dependent changes in sympathoexcitatory medullary neuron spinal connectivity, as measured using FluoroGold tracing; and 3) the extent of aberrant afferent plasticity within the lumbosacral region of the spinal cord, which has been linked to the development of autonomic dysreflexia. We believe that this model, which utilizes equipment common to numerous SCI laboratories, can serve as a research standard for studies specifically aimed at investigating autonomic neuroprotective and regenerative strategies following SCI.