Journal of neurotrauma
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Journal of neurotrauma · Feb 2020
Transcutaneous spinal cord stimulation induces temporary attenuation of spasticity in individuals with spinal cord injury.
Epidural spinal cord stimulation (SCS) is currently regarded as a breakthrough procedure for enabling movement after spinal cord injury (SCI), yet one of its original applications was for spinal spasticity. An emergent method that activates similar target neural structures non-invasively is transcutaneous SCS. Its clinical value for spasticity control would depend on inducing carry-over effects, because the surface-electrode-based approach cannot be applied chronically. ⋯ We further conducted a single-case multi-session study over 6 weeks to explore the applicability of transcutaneous SCS as a home-based therapy. Self-application of the intervention was successful; weekly evaluations suggested progressively improving therapeutic effects during the active period and carry-over effects for 7 days. Our results suggest that transcutaneous SCS can be a viable non-pharmacological option for managing spasticity, likely working through enhancing pre- and post-synaptic spinal inhibitory mechanisms, and may additionally serve to identify responders to treatments with epidural SCS.
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Journal of neurotrauma · Feb 2020
A novel multidimensional analysis of rodent gait reveals the compensation strategies employed during spontaneous recovery from spinal cord and traumatic brain injury.
As rodent locomotion becomes a more popular behavioral assay, proper rodent gait analysis becomes more and more important. Gait measures, such as stride length, cycle time, and duty factor, are not independent of one another, making statistical comparisons between groups a tricky endeavor. Instead of identifying the mathematical relationships between a group of locomotor measures, we simply tracked the steps of rodents in x,y,t space. ⋯ Our new gait analysis technique helps to show the trade-off between the restoration of function and the spontaneous development of compensatory techniques. When we applied this new analysis technique to 13 mice after a severe controlled cortical impact, we found that their locomotion was no different from 12 sham mice for the entire 4 weeks of the study. We believe that this gait analysis method succinctly addresses the confound of interdependency of gait measures and does so across multiple injury models.
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Journal of neurotrauma · Feb 2020
TMEM176A and TMEM176B are candidate regulators of inhibition of dendritic cell maturation and function after chronic spinal cord injury.
Inhibition of dendritic cell maturation and activation, together with abnormal functioning of cell-mediated immunity, has been reported in chronic spinal cord injury (SCI). The development of immune-based therapies could: 1) prevent or slow down limit further tissue damage in chronic SCI, and 2) promote tissue regeneration. To identify novel candidate molecular pathways mediating SCI-induced immune changes, we performed whole-genome microarray and molecular pathway analyses. ⋯ Here, we report overexpression of both genes in SCI compared with control subjects. Thus, we propose that TMEM176A and TMEM176B are candidate genes involved in inhibiting protective immune responses in SCI. This study may support future research aimed at developing new targets for therapies to promote immune system-mediated neuroprotection and recovery in SCI.
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Journal of neurotrauma · Feb 2020
Inhibition of ADAMTS-4 expression in olfactory ensheathing cells enhances recovery after transplantation within spinal cord injury.
Spinal cord injury (SCI) induces permanent loss of sensitive and motor functions below the injury level. To date, a wide variety of cells has been used as biotherapies to cure SCI in different animal paradigms. Specifically, olfactory ensheathing cells (OECs) is one of the most promising. ⋯ Taking advantage of ADAMTS4-/- mouse line, we produce ADAMTS4 deficient primary OEC cultures and then we investigated their regenerative potential after SCI. By using quantitative polymerase chain reaction, bioluminescence imaging, measurement of locomotor activity, electrophysiological studies, and immunohistochemistry, our results show that ADAMTS4-/- olfactory bulb OEC (bOECs) primary cultures upregulate their trophic factor expression in vitro, and that the transplantation of ADAMTS4-/- bOECs in a severe SCI model increases functional recovery and tissue repair in vivo. Altogether, our study reveals, for the first time, that primary bOEC cultures transplantation can be potentialized by inhibition of the expression of ADAMTS4.
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Journal of neurotrauma · Feb 2020
Possible strategies to optimize a biomarker discovery approach to correlate with neurological outcome in patients with spinal cord injury: a pilot study.
The lack of reliable diagnostic and prognostic markers for spinal cord injured (SCI) patients is a severe obstacle in development and testing of new therapies, and it also impairs appropriate rehabilitation care. The sparse available data on the biochemical composition of cerebrospinal fluid (CSF) during the acute and/or chronic phase of the lesion provide, up until now, inconsistent results. In this pilot study, we then explored the possibility of combining a multi-parametric and bioinformatic analysis of CSF for its biological properties tested on different cells types, suitable for investigating inflammation and re-myelination. ⋯ A bioinformatic analysis indicated that interleukin (IL)-6 and IL-10 are in the core of the interconnected net of activated proteins. Cell-based experiments indicate that CSF from SCI patients stimulates astroglia derivation from neural precursor cells, and an inverse correlation between IL-8 CSF level and oligodendrocyte precursor cells generated from neural stem cells was also observed. Results from this pilot study suggest that using a combined bioanalytic and biological approach to analyze SCI CSF at different times after injury could be a useful approach for identifying reliable diagnostic and prognostic markers in SCI.