Journal of neurotrauma
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Journal of neurotrauma · Mar 2017
RNA binding protein HuR is Translocated in Astrocytes Following Spinal Cord Injury and Promotes the Inflammatory Response.
Inflammation plays a prominent role in the events following traumatic injury to the central nervous system (CNS). The initial inflammatory response is driven by mediators such as tumor necrosis factor α and interleukin 1β, which are produced by activated astrocytes and microglia at the site of injury. These factors are regulated post-transcriptionally by RNA binding proteins (RBP) that interact with adenylate and uridylate-rich elements (ARE) in the 3'-untranslated region of the messenger RNA (mRNA). ⋯ A small molecule inhibitor of HuR suppressed cytokine induction of injured astrocytes and reduced chemoattraction for neutrophils and microglia. In summary, HuR is activated in astrocytes in the early stages of CNS trauma and positively regulates the molecular response of key inflammatory mediators in astrocytes. Our findings suggest that HuR may be a therapeutic target in acute CNS trauma for blunting secondary tissue injury triggered by the inflammatory response.
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Journal of neurotrauma · Mar 2017
High-intensity locomotor exercise increases brain-derived neurotrophic factor in individuals with incomplete spinal cord injury.
High-intensity locomotor exercise is suggested to contribute to improved recovery of locomotor function after neurological injury. This may be secondary to exercise-intensity-dependent increases in neurotrophin expression demonstrated previously in control subjects. However, rigorous examination of intensity-dependent changes in neurotrophin levels is lacking in individuals with motor incomplete spinal cord injury (SCI). ⋯ Significant correlations were observed between changes in BDNF and specific indicators of exercise intensity (e.g., rating of perceived exertion; R = 0.43; p = 0.02). Additionally, the data suggest that Val66Met SNP carriers may not exhibit intensity-dependent changes in serum BDNF concentration. Given the known role of BDNF in experience-dependent neuroplasticity, these preliminary results suggest that exercise intensity modulates serum BDNF concentrations and may be an important parameter of physical rehabilitation interventions after neurological injury.
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Journal of neurotrauma · Mar 2017
Pain Input Impairs Recovery After Spinal Cord Injury: Treatment With Lidocaine.
More than 90% of spinal cord injuries are caused by traumatic accidents and are often associated with other tissue damage (polytrauma) that can provide a source of continued pain input during recovery. In a clinically relevant spinal cord contusion injury model, prior work has shown that noxious stimulation at an intensity that engages pain (C) fibers soon after injury augments secondary injury and impairs functional recovery. Noxious input increases the expression of pro-inflammatory cytokines (interleukin 1β and 18), cellular signals associated with cell death (caspase 3 and 8), and physiological signs of hemorrhage. ⋯ Contused rats that received nociceptive stimulation soon after injury exhibited poor locomotor recovery, less weight gain, and greater tissue loss at the site of injury. Prophylactic application of lidocaine blocked the adverse effect of nociceptive stimulation on behavioral recovery and reduced tissue loss from secondary injury. The results suggest that quieting neural excitability using lidocaine can reduce the adverse effect of pain input (from polytrauma or surgery) after SCI.
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Journal of neurotrauma · Mar 2017
Increased Central Arterial Stiffness after Spinal Cord Injury: Contributing Factors, Implications and Possible Interventions.
Individuals with spinal cord injury (SCI) experience life-threatening cardiovascular events and various autonomic consequences in addition to the well-appreciated motor and neurological impairments. As a result, cardiovascular disease is a major cause of death after SCI, corresponding to a two-to-fourfold increased risk of cardiovascular events. A combination of neuroanatomical changes, unstable blood pressure, and rapid deconditioning as a result of decreased physical activity likely contributes to accelerated cardiovascular disease progression after SCI. ⋯ The potential factors contributing to increased central arterial stiffness are also reviewed in light of the available literature, including autonomic disruptions, blood pressure instability, metabolic changes, and physical inactivity. Further, measurement techniques, risk factors, cardiac dysfunction, and differences in arterial stiffness from able-bodied populations are discussed. Finally, potential therapeutic interventions for preventing or improving central arterial stiffening are also explored, including dietary, physical activity, and pharmacological strategies.