Journal of neurotrauma
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Journal of neurotrauma · May 2022
ANP and ENaC contribute to spinal cord injury-induced polyuria in mice.
Polyuria is found in patients with spinal cord injury (SCI). However, the underlying cellular and molecular mechanism is unknown. Here, we show that mice had elevated urine for 7 days after T10 contusion. ⋯ An NPR-A inhibitor (A71915) given intravenously eliminated the effects of SCI on ENaC and polyuria. These data together with previous studies suggest that SCI causes polyuria, probably by reducing ENaC activity through elevating ANP and NPR-A. Further investigation of the signal transduction pathways may provide useful information for discovering an efficient drug to treat SCI-induced polyuria.
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Journal of neurotrauma · May 2022
The impact of surgical timing on motor level lowering in motor complete traumatic spinal cord injury patients.
Patients with complete traumatic spinal cord injury (tSCI) have a low potential to recover ambulation. Motor level recovery, adjacent to the level of injury, could influence functional independency. This study addresses whether surgical timing influences motor level recovery in patients with motor complete (American Spinal Injury Association [ASIA] Impairment Scale A [AIS A]) and motor incomplete (AIS B) tSCI. ⋯ The presence of sacral sparing (AIS B) at initial examination, and cervical level of the tSCI were associated with ≥1 motor level lowering. In addition, AO Spine C-type injuries were negatively associated with any type of neurological recovery, except motor level lowering. Although sensorimotor complete injuries as well as thoracolumbar injuries negatively influence neurological recovery, early surgical decompression (< 24 h) appears independently associated with enhanced neurological recovery in patients with traumatic spinal cord injury despite level and severity of injury.
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Journal of neurotrauma · May 2022
Administration of C5a receptor antagonist improves the efficacy of human iPSCs-derived NS/PC transplantation in the acute phase of spinal cord injury.
Human-induced pluripotent stem cell-derived neural stem/progenitor cell (hiPSC-NS/PC) transplantation during the acute phase of spinal cord injury (SCI) is not effective due to the inflammatory response occurring immediately after SCI, which negatively impacts transplanted cell survival. Therefore, we chose to study the powerful chemoattractant complement C5a as a method to generate a more favorable transplantation environment. We hypothesized that suppression of the inflammatory response immediately after SCI by C5a receptor antagonist (C5aRA) would improve the efficacy of hiPSC-NS/PCs transplantation for acute phase SCI. ⋯ The C5aRA+TP group also had a significantly higher cell survival rate compared with the PBS+TP group. This study demonstrates that administration of C5aRA can suppress the inflammatory response during the acute phase of SCI, while improving the survival rate of transplanted hiPSC-NS/PCs, as well as enhancing motor functional restoration. Human-induced pluripotent stem cell-derived neural stem/progenitor cell transplantation with C5aRA is a promising treatment during the acute injury phase for SCI patients.
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Journal of neurotrauma · May 2022
Exosomes secreted by hypoxia-preconditioned adipose-derived mesenchymal stem cells reduce neuronal apoptosis in rats with spinal cord injury.
Neuronal death is the main cause of nerve function impairment after spinal cord injury (SCI). Exosome-based therapy has become a novel strategy for tissue injury repair. We designed a method to treat SCI using exosomes secreted by adipose tissue-derived stromal cells (ADSCs) under hypoxic conditions. ⋯ Through real-time polymerase chain reaction, dual luciferase reporter assays and signaling pathway chip analysis, we determined that miR-499a-5p regulates the JNK3/c-jun-apoptotic signaling pathway by targeting JNK3. Further, we verified the expression of the key proteins in the JNK3/c-jun-apoptotic signaling pathway by immunofluorescence and Western blotting. These results support the hypothesis that Hypo-exo can reduce neuronal apoptosis after SCI and may provide new methods to treat SCI.
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Journal of neurotrauma · May 2022
Review Meta AnalysisMapping the long rocky road to effective spinal cord injury therapy - A meta-review of pre-clinical and clinical research.
Spinal cord injury (SCI) is a rare condition, which even after decades of research, to date still presents an incurable condition with a complex symptomatology. An SCI can result in paralysis, pain, loss of sensation, bladder and sexual dysfunction, and muscle degeneration, to name but a few. The large number of publications makes it difficult to keep track of current progress in the field and of the many treatment options that have been suggested and are being proposed with increasing frequency. ⋯ Using the example of SCI research, our findings demonstrate the challenges that come with the accelerating research progress-an issue that many research fields are faced with today. The analyses point out similarities and differences in the prioritization of SCI research in pre-clinical versus clinical therapy strategies. Moreover, the results demonstrate the rapidly growing importance of modern (bio-)engineering technologies.