Journal of neurotrauma
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Journal of neurotrauma · Nov 2019
Differences in Morphometric Measures of the Uninjured Porcine Spinal Cord and Dural Sac Predict Histological and Behavioral Outcomes after Traumatic Spinal Cord Injury.
One of the challenges associated with conducting experiments in animal models of traumatic spinal cord injury (SCI) is inducing a consistent injury with minimal variability in the degree of tissue damage and resultant behavioral and biochemical outcomes. We evaluated how the variability in morphometry of the spinal cord and surrounding cerebrospinal fluid (CSF) contributes to the variability in behavioral and histological outcomes in our porcine model of SCI. Using intraoperative ultrasound imaging, spinal cord morphometry was assessed in seven Yucatan minipigs undergoing a weight-drop T10 contusion-compression injury. ⋯ In addition, a dorsoventral diameter of the spinal cord less than 5.331 mm was a strong contributing factor to poor behavioral recovery over 12 weeks. These results indicate that interanimal variability in cord morphometry provides a potential biological explanation for the observed heterogeneity in histological and behavioral outcomes. Such knowledge is helpful for appropriately balancing experimental groups, and/or varying impact parameters to match cord and CSF layer dimensions for future studies.
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Journal of neurotrauma · Nov 2019
Development of a novel gait analysis tool measuring center of pressure for evaluation of canine chronic thoracolumbar spinal cord injury.
Gait evaluation after spinal cord injury (SCI) is an important component of determining functional status. Analysis of center of pressure (COP) provides a dynamic reflection of global locomotion and postural control and has been used to quantify various gait abnormalities. We hypothesized that COP variability would be greater for SCI versus normal dogs and that COP would be able to differentiate varying injury severity. ⋯ Support percentage moderately correlated with SS (p = 0.019; R2 = 0.47). COP analysis and body weight support measurements offer information about post-injury locomotion. Further development is needed before consideration as an outcome measure to complement validated gait analysis methods in dogs with SCI.
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Journal of neurotrauma · Nov 2019
Systemic inhibition of soluble TNF with XPro1595 exacerbates a post-spinal cord injury depressive phenotype in female rats.
Spinal cord injury (SCI) is associated with a three-fold risk of major depressive disorder compared with the general population. Current antidepressant therapy is often not as effective in this patient population, suggesting the need for a more efficacious therapeutic target. The goal of this study was to elucidate the role of inflammatory cytokine tumor necrosis factor (TNF) in the dorsal raphe nucleus (DRN, the principle source of serotonin to the brain) in the development and possible treatment of depression after SCI. ⋯ Subcutaneous (s.c.) delivery of XPro1595 caused an exacerbation of depressive phenotype, with all treated clusters exhibiting increased forced swim immobility compared with saline-treated non-depressed rats. Intracerebroventricular (i.c.v.) administration of the drug did not prevent or enhance the development of depression after injury. These results suggest a complex role for TNF-based neuroinflammation in SCI-induced depression that needs to be further explored, perhaps in conjunction with a broader targeting of additional post-SCI inflammatory cytokines.
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Journal of neurotrauma · Nov 2019
Modulation of serotonin and adenosine 2A receptors on intermittent hypoxia-induced respiratory recovery following mid-cervical contusion in the rat.
The present study was designed to evaluate the therapeutic effectiveness and mechanism of acute intermittent hypoxia on respiratory function at distinct injury stages following mid-cervical spinal contusion. In the first experiment, adult male rats received laminectomy or unilateral contusion at 3rd-4th cervical spinal cord at 9 weeks of age. The ventilatory behavior in response to mild acute intermittent hypercapnic-hypoxia (10 episodes of 5 min of hypoxia [10% O2, 4% CO2, 86% N2] with 5 min of normoxia intervals) was measured by whole-body plethysmography at the acute (∼3 days), subchronic (∼2 weeks), and chronic (∼8 weeks) injury stages. ⋯ The results demonstrated that acute intermittent hypercapnic-hypoxia-induced enhancement of minute ventilation was attenuated by a serotonin receptor antagonist (methysergide) but enhanced by an adenosine 2A receptor antagonist (KW6002) at the subchronic and chronic injury stages. These results suggested that acute intermittent hypercapnic-hypoxia can induce respiratory recovery from acute to chronic injury stages. The therapeutic effectiveness of intermittent hypercapnic-hypoxia is dampened by the inhibition of serotonin receptors, but a blockade of adenosine 2A receptors enhanced respiratory recovery induced by intermittent hypercapnic-hypoxia.
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Journal of neurotrauma · Nov 2019
Neuroectodermal stem cells grafted into the injured spinal cord induce both axonal regeneration and morphological restoration via multiple mechanisms.
Spinal cord contusion injury leads to severe loss of gray and white matter and subsequent deficit of motor and sensory functions below the lesion. In this study, we investigated whether application of murine clonal embryonic neuroectodermal stem cells can prevent the spinal cord secondary damage and induce functional recovery. Stem cells (NE-GFP-4C cell line) were grafted intraspinally or intravenously immediately or one week after thoracic spinal cord contusion injury. ⋯ Treating the grafted cords with neutralizing antibodies against these four factors through the use of osmotic pumps nearly completely abolished the effect of the graft. The non-significant functional improvement after function blocking is likely because the stem cell derivatives settled in the injured cord. These data suggest that grafted neuroectodermal stem cells are able to prevent the secondary spinal cord damage and induce significant regeneration via multiple mechanisms.