Journal of neurotrauma
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Journal of neurotrauma · Nov 2017
Characterization of chronic axonal degeneration using diffusion tensor imaging in canine spinal cord injury: A quantitative analysis of DTI parameters according to histopathological differences.
Diffusion tensor imaging (DTI) is more sensitive than conventional magnetic resonance imaging (MRI) for the identification of axonal degeneration. However, no study to date has used DTI to evaluate the severity of axonal degeneration in canine spinal cord injury (SCI). Therefore, the aim of this study was to characterize multi-grade axonal degeneration (mild, moderate, and severe) in a canine model of spinal cord compression injury using DTI. ⋯ The severity of AxD demonstrated a negative linear correlation with fractional anisotropy and positive linear correlations with spherical index and radial diffusivity; additionally, positive U-shaped correlations were identified between the severity of AxD and mean diffusivity and axial diffusity (AD). These results demonstrate a potential clinical application for DTI in the noninvasive monitoring of histological changes post-SCI. DTI could be utilized for the early diagnosis and assessment of SCI and, ultimately, used to optimize the treatment and rehabilitation of SCI patients.
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Journal of neurotrauma · Nov 2017
Testosterone Plus Finasteride Prevents Bone Loss Without Prostate Growth in a Rodent Spinal Cord Injury Model.
We have reported that testosterone-enanthate (TE) prevents the musculoskeletal decline occurring acutely after spinal cord injury (SCI), but results in a near doubling of prostate mass. Our purpose was to test the hypothesis that administration of TE plus finasteride (FIN; type II 5α-reductase inhibitor) would prevent the chronic musculoskeletal deficits in our rodent severe contusion SCI model, without inducing prostate enlargement. Forty-three 16-week-old male Sprague-Dawley rats received: 1) SHAM surgery (T9 laminectomy); 2) severe (250 kdyne) contusion SCI; 3) SCI+TE (7.0 mg/week, intramuscular); or 4) SCI+TE+FIN (5 mg/kg/day, subcutaneous). ⋯ FIN coadministration did not inhibit the TE-induced musculoskeletal effects, but prevented prostate growth. Neither drug regimen prevented SCI-induced cortical bone loss, although no differences in whole bone strength were present among groups. Our findings indicate that TE+FIN prevented the chronic cancellous bone deficits and LABC muscle loss in SCI animals without inducing prostate enlargement, which provides a rationale for the inclusion of TE+FIN in multimodal therapeutic interventions intended to alleviate the musculoskeletal decline post-SCI.
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Journal of neurotrauma · Nov 2017
Anatomical recruitment of spinal V2a interneurons into phrenic motor circuitry after high cervical spinal cord injury.
More than half of all spinal cord injuries (SCIs) occur at the cervical level, often resulting in impaired respiration. Despite this devastating outcome, there is substantial evidence for endogenous neuroplasticity after cervical SCI. Spinal interneurons are widely recognized as being an essential anatomical component of this plasticity by contributing to novel neuronal pathways that can result in functional improvement. ⋯ Transneuronal tracing with pseudorabies virus (PRV) was used to identify interneurons within the phrenic circuitry. There was a robust increase in the number of PRV-labeled V2a interneurons ipsilateral to the C2 hemisection, demonstrating that significant numbers of these excitatory spinal interneurons were anatomically recruited into the phrenic motor pathway two weeks after injury, a time known to correspond with functional phrenic plasticity. Understanding this anatomical spinal plasticity and the neural substrates associated with functional compensation or recovery post-SCI in a controlled, experimental setting may help shed light onto possible cellular therapeutic candidates that can be targeted to enhance spontaneous recovery.
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Journal of neurotrauma · Nov 2017
Fumaric Acid Esters Attenuate Secondary Degeneration Following Spinal Cord Injury.
Spinal cord injury (SCI) causes permanent changes in motor, sensory, and autonomic functions. Unfortunately, there are no stable cures and current treatments include surgical decompression, methylprednisolone, and hemodynamic control that lead to modest function recovery. Fumaric acid esters (FAEs) were firstly used in the management of an immunological skin disorder, such as psoriasis. ⋯ FAEs significantly reduced the severity of inflammation by a modulation of pro-inflammatory cytokines and apoptosis factors, and increased neutrophic factors such as anti-brain-derived neurotrophic factor (BDNF), anti-glial cell-derived neurotrophic factor (GDNF), and neurotrophin-3 (NT3). Our results showed important protective effects of DMF in an animal model of SCI, considerably improving recovery of motor function, possibly by reducing the secondary inflammation and tissue injury that characterize this model. DMF may constitute a promising target for future SCI therapies.
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Journal of neurotrauma · Nov 2017
Effects of multiple-injection of bone marrow mononuclear cells on spinal cord injury of rats.
The effects of multiple injection of bone marrow mononuclear cells (BMNCs) on spinal cord injury (SCI) were compared with those of single injection in rats. BMNCs separated by density-gradient centrifugation from a bone marrow perfusate were injected three times (once weekly) through the cerebrospinal fluid (CSF) via the fourth ventricle, and the locomotor improvement and tissue recovery, including axonal regeneration, were compared with those of single injection. While the single-injection group showed a steep elevation of the Basso-Beattie-Bresnahan (BBB) score 1 week after transplantation, the multiple-injection group maintained a similar steep elevation for 2 weeks after transplantation, and the BBB scores of the multiple-injection group remained thereafter at a level approximately 2-3 points higher than those of the single-injection group until the end of the experiment. ⋯ There were, however, no significant differences in the density of regenerating axons or volumes of cavities between the single- and multiple-injection groups. These results showed that although tissue recoveries were similar between single and multiple injection, the multiple injection of BMNCs was more beneficial for locomotor improvement than single injection for the treatment of SCI. Considering the technically simple and low-cost procedures for the preparation and injection of BMNCs, multiple injection of BMNCs by lumbar puncture has an advantage over single injection on clinical application.