Journal of neurotrauma
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Journal of neurotrauma · Sep 2019
Randomized Controlled TrialLow-Dose Testosterone and Evoked Resistance Exercise after Spinal Cord Injury on Cardio-Metabolic Risk Factors: An Open-Label Randomized Clinical Trial.
The purpose of the work is to investigate the effects of low-dose testosterone replacement therapy (TRT) and evoked resistance training (RT) on body composition and metabolic variables after spinal cord injury (SCI). Twenty-two individuals with chronic motor complete SCI (ages 18-50 years) were randomly assigned to either TRT+RT (n = 11) or TRT (n = 11) for 16 weeks following a 4 -week delayed entry period. TRT+RT men underwent twice weekly progressive RT using electrical stimulation with ankle weights. ⋯ IGFBP-3 increased (p = 0.0001) while IL-6 decreased (p = 0.039) following both interventions, and TRT+RT suppressed adiponectin (p = 0.024). TRT+RT resulted in an increase in LM and whole thigh and knee extensor muscle CSAs, with an increase in BMR and suppressed adiponectin. Low-dose TRT may mediate modest effects on visceral adipose tissue, Sg, IGFBP-3, and IL-6, independent of changes in LM.
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Journal of neurotrauma · Sep 2019
Bisperoxovanadium mediates neuronal protection through inhibition of PTEN and activation of PI3K/AKT-mTOR signaling following traumatic spinal injuries.
Although mechanisms involved in progression of cell death in spinal cord injury (SCI) have been studied extensively, few are clear targets for translation to clinical application. One of the best-understood mechanisms of cell survival in SCI is phosphatidylinositol-3-kinase (PI3K)/Akt and associated downstream signaling. Clear therapeutic efficacy of a phosphatase and tensin homologue (PTEN) inhibitor called bisperoxovanadium (bpV) has been shown in SCI, traumatic brain injury, stroke, and other neurological disease models in both neuroprotection and functional recovery. ⋯ Conversely, PTEN activity appeared to increase over this period. As observed in vitro, bpV also increased Erk activity post-SCI (p < 0.05). Our results suggest that PI3K/Akt signaling is the likely primary mechanism of bpV action in mediating neuroprotection in injured spinal neurons.
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Journal of neurotrauma · Sep 2019
Melatonin treatment alleviates spinal cord injury-induced gut dysbiosis in mice.
Spinal cord injury (SCI) disturbs the autonomic nervous system and induces dysfunction in multiple organs/tissues, such as the gastrointestinal (GI) system. The neuroprotective effects of melatonin in SCI models have been reported; however, it is unclear whether the beneficial effects of melatonin are associated with alleviation of gut dysbiosis. In this study, we showed that daily intraperitoneal injection with melatonin following spinal cord contusion at thoracic level 10 in mice improved intestinal barrier integrity and GI motility, reduced expression levels of certain proinflammatory cytokines, improved animal weight gain and metabolic profiling, and promoted locomotor recovery. ⋯ Melatonin-treated SCI animals showed decreased relative abundance of Clostridiales and increased relative abundance of Lactobacillales and Lactobacillus, which correlated with alteration of cytokine (monocyte chemotactic protein 1) expression and GI barrier permeability, as well as with locomotor recovery. Experimental induction of gut dysbiosis in mice before SCI (i.e., by oral delivery of broad-spectrum antibiotics) exacerbates neurological impairment after SCI, and melatonin treatment improves locomotor performance and intestinal integrity in antibiotic-treated SCI mice. The results suggest that melatonin treatment restores SCI-induced alteration in gut microbiota composition, which may underlie the ameliorated GI function and behavioral manifestations.
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We previously reported the serendipitous observation that fenbendazole, a benzimidazole anthelmintic, improved functional and pathological outcomes following thoracic spinal cord contusion injury in mice when administered pre-injury. Fenbendazole is widely used in veterinary medicine. However, it is not approved for human use and it was uncertain if only post-injury administration would offer similar benefits. ⋯ Histological analysis of spinal cord sections showed that such treatment with flubendazole also reduced lesion volume and improved total tissue sparing, white matter sparing, and gray matter sparing. Flubendazole inhibited the activation of glial fibrillary acidic protein (GFAP); suppressed cyclin B1 expression and Bruton tyrosine kinase activation, markers of B cell activation/proliferation and inflammation; and reduced B cell autoimmune response. Together, these results suggest the use of the benzimidazole anthelmintic flubendazole as a potential therapeutic for SCI.
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Journal of neurotrauma · Sep 2019
An accurate method for histological determination of neural tissue loss/sparing following compression-induced spinal cord injury with optimal reproducibility.
In addition to behavioral testing, the efficacy of neuroprotective therapies applied after spinal cord injury (SCI) is commonly evaluated by means of histological quantification of spared neural tissue. The primary insult itself, but mainly the pathological processes of secondary injury are the underlying causes of spinal tissue degeneration, the extent of which depends on the injury severity and post-injury time. ⋯ To overcome the problem, our new quantification approach combines a modified method for predicting the cross-sectional area at the lesion site with semi-automatic measurement of spared neural tissue and cystic cavities, using freely accessible National Institutes of Health (NIH) ImageJ software, with a Java-based image processing program. Based on the histological parameters measured after differing compression-induced SCI and correlated with behavioral outcomes, we can conclude that our new method is relatively fast, accurate, and optimally reproducible.