Journal of neurotrauma
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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
Systemic administration of Connexin43 mimetic peptide improves functional recovery following traumatic spinal cord injury in adult rats.
Blocking of Connexin43 hemichannels, the main gap junction protein located on astrocytes in the central nervous system, has been shown to reduce neural injury in a number of models. We demonstrated previously that local administration of a Connexin43 mimetic peptide, Peptide5, reduces secondary tissue damage after spinal cord injury (SCI). Here, we investigated whether acute systemic delivery of Peptide5 is also protective in a model of SCI. ⋯ At two and six weeks, lesion size, the astrocytic and the activated macrophage, and/or microglial response were all decreased in the Peptide5 animals. In addition, neuronal cell numbers were higher in the Peptide5 animals compared with the scrambled peptide treated rats at two and six weeks. These results show for the first time that systemic administration of Peptide5 to block the pathological opening of Connexin43 hemichannels is a feasible treatment strategy in this setting, ameliorating the secondary SCI.
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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
Risk of Dementia in Patients with Spinal Cord Injury: A Nationwide Population-Based Cohort Study.
Spinal cord injury (SCI) can cause physical disability and psychological distress; however, whether SCI is a risk factor for dementia is unclear. This study evaluated the incidence of dementia in patients with SCI. Study participants were recruited from a nationwide cohort during 2004-2007 and categorized into SCI (patients diagnosed with SCI; n = 941) and non-SCI (age- and sex-matched controls; n = 5060) cohorts. ⋯ Patients with SCI had a significantly higher risk of dementia than did those without SCI (crude hazard ratio [HR] = 2.14, 95% confidence interval [CI], 1.57-2.92, p < 0.001 vs. adjusted HR = 1.95, 95% CI, 1.43-2.67, p < 0.001). Further analysis found that there is no statistical significance of higher risk for developing Alzheimer's disease among SCI patients, but that SCI patients were at higher risk of developing other types of dementia than the control cohort (crude HR = 1.88, 95% CI, 1.33-2.63, p < 0.001 vs. adjusted HR = 1.90, 95% CI, 1.35-2.68, p < 0.001). In conclusion, patients with SCI are at high risk of dementia, and effective dementia prevention strategies are recommended for comprehensive SCI care.
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Journal of neurotrauma · Feb 2017
Left ventricular mechanics in untrained and trained males with tetraplegia.
Reduced left ventricular (LV) function is common in tetraplegia, yet it is unknown whether intrinsic myocardial function is attenuated. This study examined the effect of SCI and exercise-training status on LV mechanics (intrinsic function) and LV systolic/diastolic function by comparing untrained (UT) and trained (TT) individuals with tetraplegia and able-bodied (AB) individuals. Individuals with tetraplegia had a traumatic, chronic, motor-complete cervical spinal cord injury. ⋯ Diastolic mechanics (apical circumferential strain rate) were significantly enhanced in TT (3.03 ± 0.83 s-1) compared to AB (1.85 ± 0.65 s-1; p < 0.05). There was a trend (p = 0.062) for a between-group difference in apical radial diastolic strain rate (UT: -2.51 ± 0.83 s-1; TT: -3.92 ± 1.96 s-1; AB: -1.84 ± 0.46 s-1). In tetraplegia, attenuated LV systolic function is not attributed to intrinsic dysfunction, whereas exercise-training status appears to improve both global LV diastolic function and LV mechanics.