Journal of neurotrauma
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Journal of neurotrauma · Aug 2022
Control of fore- and hindlimb movements and their coordination during quadrupedal locomotion across speeds in adult spinal cats.
Coordinating the four limbs is critical for terrestrial mammalian locomotion. Thoracic spinal transection abolishes neural communication between the brain and spinal networks controlling hindlimb/leg movements. Several studies have shown that animal models of spinal transection (spinalization), such as mice, rats, cats, and dogs recover hindlimb locomotion with the forelimbs stationary or suspended. ⋯ Coordination between the forelimbs and hindlimbs was weakened and more variable in the spinal state. Changes in muscle activity reflected spatiotemporal changes in the locomotor pattern. Despite important changes in the pattern, our results indicate that biomechanical properties of the musculoskeletal system play an important role in quadrupedal locomotion and offset some of the loss in neural communication between networks controlling the forelimbs and hindlimbs after spinal transection.
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Journal of neurotrauma · Aug 2022
Advanced Age and Neurotrauma Diminish Glutathione and Impair Antioxidant Defense after Spinal Cord Injury.
Advanced age at the time of spinal cord injury (SCI) exacerbates damage from reactive oxygen species (ROS). Mechanisms underlying this age-dependent response are not well understood and may arise from decreased antioxidant defense. We investigated how spinal cord levels of the antioxidant glutathione (GSH), and its regulation, change with age and SCI. ⋯ NACA treatment restored GSH and improved the redox environment in injured 4- and 14-MO mice at one dpi; however, three days of NACA delivery did not improve motor, sensory, or anatomical deficits at 28 dpi in 4-MO mice and trended toward toxicity in all outcomes in 14-MO mice. Our observation suggests that GSH levels at acute stages of SCI play a minimal role in age-dependent outcomes reported after SCI in mice. Collective results implicate elements of injury occurring after three dpi, such as inflammation, as key regulators of age-dependent effects.
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Journal of neurotrauma · Aug 2022
Immunoglobulin G is Increased in the Injured Spinal Cord in a Sex and Age Dependent Manner.
There are limited studies examining age and sex as biological variables in the pathophysiology of spinal cord injury (SCI). The use of older animals and sex-balanced groups in SCI models is increasingly prioritized to better match clinical demographics. Including older animals in SCI studies is technically challenging, and outcomes are unpredictable with respect to biological and treatment responses. ⋯ Because IgG was elevated in an age- and sex-dependent manner without of evidence of differences in hemorrhage, our findings point to potential pre-existing differences in IgG within mouse plasma in an age- and sex-dependent manner. This report has identified age- and sex-dependent differences in infiltrating IgG into the injured spinal cord environment that may affect injury and recovery processes. Our findings highlight that systemic contributions to SCI can be sex- and age-dependent and illustrate the value of reporting incidental discoveries.
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Journal of neurotrauma · Aug 2022
Exosome-shuttled miR-672-5p from anti-inflammatory microglia repair traumatic spinal cord injury by inhibiting AIM2/ASC/Caspase-1 signaling pathway mediated neuronal pyroptosis.
Traumatic spinal cord injury (TSCI) is a devastating traumatic disease of the central nervous system, which leads to refractory loss of motor and sensory function. So far, there is no effective treatment for TSCI. Recently, however, nano-sized exosomes from various spinal cord cells have shown great prospects in the treatment of various diseases, including TSCI. ⋯ Through a series of experiments, we also confirmed that miR-672-5p is the most critical miRNA associated with M2-Exos, and that its targeting gene is AIM2. M2-Exos rich in miR-672-5p could inhibit the AIM2/ASC/caspase-1 signaling pathway by inhibiting AIM2 activity, so as to inhibit neuronal pyroptosis and finally promote the recovery of functional behavior in mice with TSCI. In conclusion, our study suggests that the application of M2-Exos may be a promising treatment strategy for TSCI.
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Journal of neurotrauma · Aug 2022
Fatty acid-binding protein 4 (FABP4) inhibition promotes locomotor and autonomic recovery in rats following spinal cord injury.
The inflammatory response associated with traumatic spinal cord injury (SCI) contributes to locomotor and sensory impairments. Pro-inflammatory (M1) macrophages/microglia (MϕMG) are the major cellular players in this response as they promote chronic inflammation resulting in injury expansion and tissue damage. Fatty acid-binding protein 4 (FABP4) promotes M1 MϕMG differentiation; however, it is unknown if FABP4 also plays a role in the etiology of SCI. ⋯ Additionally, inhibitor-treated rats exhibit enhanced autonomic bladder reflex recovery. Immunofluorescence experiments also show the administration of the FABP4 inhibitor increases the number of CD163+ and liver arginase+ M2 MϕMG within the epicenter and penumbra of the injured spinal cord 28 days post-injury. These findings show that FABP4 may significantly exacerbate locomotor and sensory impairments during SCI by modulating macrophage/microglial activity.