Journal of neurotrauma
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Journal of neurotrauma · Mar 2019
Activating Adiponectin Signaling with Exogenous AdipoRon Reduces Myelin Lipid Accumulation and Suppresses Macrophage Recruitment after Spinal Cord Injury.
Myelin-laden macrophages (mye-MΦ), resulting primarily from internalization of myelin debris by infiltrating bone marrow-derived macrophages in spinal cord injury (SCI), trigger inflammatory responses that largely contribute to secondary injury. Adiponectin, which is secreted from adipose tissue, is an important hormone that modulates macrophage inflammation. In the present study, we examined the role of adiponectin on macrophage-mediated neuroinflammation after SCI. ⋯ In vivo data further confirmed that intravenous administration of AdipoRon after SCI dampened recruitment of macrophages and reduced myelin lipid accumulation. Accordingly, AdipoRon treatment ameliorated post-SCI tissue damage and astrogliosis, resulting in improved motor function. Although there was no significant pathological exacerbation in adiponectin-null mice subjected to SCI, our work reveals a functional link between adiponectin and hematogenous macrophages in the context of SCI, suggesting that activation of adiponectin signaling is a promising therapeutic approach to mitigate mye-MΦ-mediated neuroinflammation in neurological disorders involving demyelination.
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Journal of neurotrauma · Mar 2019
Extent of Spinal Cord Decompression in Motor Complete (American Spinal Injury Association Impairment Scale Grades A and B) Traumatic Spinal Cord Injury Patients: Post-Operative Magnetic Resonance Imaging Analysis of Standard Operative Approaches.
Although decompressive surgery following traumatic spinal cord injury (TSCI) is recommended, adequate surgical decompression is rarely verified via imaging. We utilized magnetic resonance imaging (MRI) to analyze the rate of spinal cord decompression after surgery. Pre-operative (within 8 h of injury) and post-operative (within 48 h of injury) MRI images of 184 motor complete patients (American Spinal Injury Association Impairment Scale [AIS] grade A = 119, AIS grade B = 65) were reviewed to verify spinal cord decompression. ⋯ The rates of decompression among patients who underwent laminectomy at one, two, three, four, or five levels were 58.3%, 68%, 78%, 80%, and 100%, respectively (p < 0.001). In multi-variate logistic regression analysis, only laminectomy was significantly associated with successful decompression (odds ratio 4.85; 95% confidence interval 2.2-10.6; p < 0.001). In motor complete TSCI patients, performing a laminectomy significantly increased the rate of successful spinal cord decompression, independent of whether anterior surgery was performed.
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Journal of neurotrauma · Mar 2019
Submaximal Marker for Investigating Peak Muscle Torque Using Neuromuscular Electrical Stimulation after Paralysis.
Spinal cord injury (SCI) results in deleterious skeletal muscle adaptations, such as relevant atrophy and loss of force. In particular, the relevant loss of lower-limb force-generating capacity may limit functional mobility even if neuronal control was sufficient. Currently, methods of assessing maximal force-generating capacity using neuromuscular electrical stimulation (NMES) are limited in individuals who cannot tolerate higher stimulation amplitudes, such as those with residual sensation and those at risk of fracture. ⋯ NMES was delivered starting with an amplitude of 5 mA, and increasing by 5 mA for every subsequent stimulation until either the participant requested to stop the stimulation or the maximum stimulation amplitude (140 mA) was reached. Significant correlations between peak slope of the recruitment curve and peak torque for all muscle groups were found (knee extensors, r = 0.75; p < 0.0001; knee flexors, r = 0.68; p < 0.0001; ankle plantarflexors, r = 0.91; p < 0.0001), indicating that muscles that show greater peak slope of the recruitment curve tend to generate a greater peak torque. This suggests that peak slope, which was achieved at an average stimulation intensity (55.0 mA) that was 43% smaller than that corresponding to peak torque (97.4 mA), may be used as a submaximal marker for characterizing maximal torque output in individuals with SCI.
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Journal of neurotrauma · Mar 2019
Diffusion Tensor Imaging Assessment of Regional White Matter Changes in the Cervical and Thoracic Spinal Cord in Pediatric Subjects.
There are no studies to date,describing changes in the diffusion tensor imaging (DTI) metrics of the white matter (WM) regions of the entire cervical and thoracic spinal cord (SC) remote from the lesion in pediatric spinal cord injury (SCI) subjects. The purpose of this study was to determine whether DTI at sites cephalad and caudal to a lesion provides measures of cord abnormalities in children with chronic SCI. A retrospective study included 10 typically developing subjects (TD) and 10 subjects with chronic SCI who underwent SC imaging in 2014-2017. ⋯ In motor tracts cephalad to the lesion, FA was significantly decreased whereas AD was significantly increased in the proximal segment; however, AD was decreased in the distal and middle segments. International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) total score was significantly correlated with FA and AD of the motor and sensory tracts cephalad to the lesion. This study demonstrates that FA and AD have the potential to be sensitive biomarkers of the full extent of cord injury and might be useful in detecting remote injuries to the SC and in guiding new treatments.
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Journal of neurotrauma · Mar 2019
Pharmacological stimulation of mitochondrial biogenesis using the FDA-approved β2-adrenoreceptor agonist formoterol for the treatment of spinal cord injury.
A hallmark of the progressive cascade of damage referred to as secondary spinal cord injury (SCI) is vascular disruption resulting in decreased oxygen delivery and loss of mitochondria homeostasis. While therapeutics targeting restoration of single facets of mitochondrial function have proven largely ineffective clinically post-SCI, comprehensively addressing mitochondrial function via pharmacological stimulation of mitochondrial biogenesis (MB) is an underexplored strategy. This study examined the effects of formoterol, a mitochondrial biogenic Food and Drug Administration-approved selective and potent β2-adrenoreceptor (ADRB2) agonist, on recovery from SCI in mice. ⋯ Importantly, locomotor capability of formoterol-treated mice was greater than vehicle-treated mice by 7 days, reaching a Basso Mouse Scale score two points greater than that of vehicle-treated SCI mice by 15 days. Interestingly, similar locomotor restoration was observed when initiation of treatment was delayed until 8 h post-injury. These data provide evidence of ADRB2-mediated MB as a therapeutic approach for the management of SCI.