Journal of neurotrauma
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Journal of neurotrauma · Aug 2013
ReviewThe therapeutic role of interleukin-10 after spinal cord injury.
Spinal cord injury (SCI) is a devastating condition affecting 270,000 people in the United States. A potential treatment for decreasing the secondary inflammation, excitotoxic damage, and neuronal apoptosis associated with SCI, is the anti-inflammatory cytokine interleukin-10. The best characterized effects of IL-10 are anti-inflammatory-it downregulates pro-inflammatory species interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6), tumor necrosis factor-α, interferon-γ, matrix metalloproteinase-9, nitric oxide synthase, myeloperoxidase, and reactive oxygen species. ⋯ A chronic systemic administration of IL-10 does not appear to be beneficial to SCI recovery and causes increased susceptibility to septicemia, pneumonia, and peripheral neuropathy. However, a localized upregulation of IL-10 has been shown to be beneficial and can be achieved by herpes simplex virus gene therapy, injection of poliovirus replicons, or surgical placement of a slow-release compound. IL-10 shows promise as a treatment for SCI, although research on local IL-10 delivery timeline and dosage needs to be expanded.
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Journal of neurotrauma · Aug 2013
Anti-apoptotic effect of microRNA-21 after contusion spinal cord injury in rats.
Multiple cellular, molecular, and biochemical changes contribute to the etiology and treatment outcome of contusion spinal cord injury (SCI). Dysregulation of microRNAs (miRNAs) has been found following SCI in recent studies. However, little is known about the functional significance of the unique role of miRNAs in SCI. ⋯ In vivo treatment with antagomir-21 increased the expression of FasL and PTEN, but did not affect PDCD4. These results suggested that miR-21 played an important role in limiting secondary cell death following SCI, and that the protective effects of miR-21 might have been the result of its regulation on pro-apoptotic genes. Thus, miR-21 may play an important role in the pathophysiology of SCI.
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Journal of neurotrauma · Aug 2013
Severity of spinal cord injury in adult and infant rats after vertebral dislocation depends upon displacement but not speed.
Spinal cord injury (SCI) is less common in children than in adults, but in children it is generally more severe. Spinal loading conditions (speed and displacement) are also thought to affect SCI severity, but the relationship between these parameters is not well understood. This study aimed to investigate the effects of vertebral speed and displacement on the severity of SCI in infants and adults using a rodent model of vertebral dislocation. ⋯ Magnitude of dislocation was found to have a different effect on the normalized area of axonal injury in adults than in infants (p=0.003). Speed of dislocation was not found to have a significant effect on normalized hemorrhage volume (p=0.427) or normalized area of axonal injury (p=0.726) independent of displacement for the range of speeds tested. The findings of this study suggest that both age and amount of spinal motion are key factors in the severity of acute SCI.
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Journal of neurotrauma · Aug 2013
Comparative StudyEpicritic sensation in cervical spinal cord injury: diagnostic gains beyond testing light touch.
Abstract Applied as a bedside test of gross dorsal column function, the testing of light touch (LT) sensation is of high clinical value in the diagnosis of human spinal cord injury (SCI). However, the assessment of overall dorsal column deficit by testing only LT may be limited, because the dorsal column pathway conveys several large diameter afferent modalities (e.g., sensation of touch, two-point discrimination, and proprioception). Therefore, the objective of this study was to compare the epicritic sensation assessed by LT, Semmes-Weinstein monofilament (SWM), and electrical perception threshold (EPT) across cervical dermatomes (C3-C8) in individuals with cervical SCI. ⋯ The degree of agreement showed considerably variable κ coefficients (-0.1≥kw≤0.7) for each dermatome between C3 and C8. The additional measurements of epicritic sensation by SWM and EPT increased sensitivity by detecting and quantifying differences in sensory thresholds above, at, and below the LT level of injury. This is relevant for early clinical trials (phase 1/2), in which disclosing any biological activity of an intervention may be revealed by subtle sensory changes that might gain a clinical relevance.
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Journal of neurotrauma · Aug 2013
Determination of urine 3-HPMA, a stable acrolein metabolite in a rat model of spinal cord injury.
Acrolein has been suggested to be involved in a variety of pathological conditions. The monitoring of acrolein is of significant importance in delineating the pathogenesis of various diseases. Aimed at overcoming the reactivity and volatility of acrolein, we describe a specific and stable metabolite of acrolein in urine, N-acetyl-S-3-hydroxypropylcysteine (3-HPMA), as a potential surrogate marker for acrolein quantification. ⋯ This finding was further validated by concomitant confirmation of increased acrolein-lysine adducts using established dot immunoblotting techniques. The noninvasive nature of measuring 3-HPMA concentrations in urine allows for long-term monitoring of acrolein in the same animal and ultimately in human clinical studies. Due to wide spread involvement of acrolein in human health, the benefits of this study have the potential to enhance human health significantly.