Journal of neurotrauma
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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.
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Journal of neurotrauma · Feb 2017
Vagal control of breathing pattern following mid-cervical contusion in rats.
The present study was designed to establish a midcervical contusion model that can simulate long-term respiratory deficits, and investigate the breathing pattern during vagal-mediated respiratory reflexes following midcervical contusion. Moderate and severe (impactor height: 6.25 or 12.5 mm) contusion was induced at midline C3-4 spinal cord in adult Sprague-Dawley rats. The ventilatory behaviors of unanesthetized were evaluated by whole body plethysmography at 1 day and 1, 2, 4, and 8 weeks post-injury. ⋯ Increased positive end-expired pressure also caused an increase in the expiratory duration in uninjured and moderately contused animals; however, severely contused animals exhibited an attenuated response. At 2 and 8 weeks post-injury, both the pulmonary chemoreflex and the Hering-Breuer inflation reflex were similar between uninjured and contused animals. These data suggested that midcervical contusion can cause a long-term respiratory impairment and a transiently attenuation of vagal-mediated respiratory reflexes.
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Journal of neurotrauma · Feb 2017
AC105 Increases Extracellular Magnesium Delivery and Reduces Excitotoxic Glutamate Exposure within Injured Spinal Cords in Rats.
Magnesium (Mg2+) homeostasis is impaired following spinal cord injury (SCI) and the loss of extracellular Mg2+ contributes to secondary injury by various mechanisms, including glutamate neurotoxicity. The neuroprotective effects of high dose Mg2+ supplementation have been reported in many animal models. Recent studies found that lower Mg2+ doses also improved neurologic outcomes when Mg2+ was formulated with polyethylene glycol (PEG), suggesting that a PEG/ Mg2+ formulation might increase Mg2+ delivery to the injured spinal cord, compared with that of MgSO4 alone. ⋯ Repeated MgSO4 infusions slightly increased the Mg2+ concentrations while saline infusion had no effect. In addition, AC105 treatment significantly reduced extracellular glutamate levels in the lesion center after SCI. These results indicate that intravenous infusion of PEG-formulated Mg2+ normalized the Mg2+ homeostasis following SCI and reduced potentially neurotoxic glutamate levels, consistent with a neuroprotective mechanism of blocking excitotoxicity.