Journal of neurotrauma
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Journal of neurotrauma · Mar 2014
Analysis of human embryonic stem cells with regulatable expression of the cell adhesion molecule L1 in regeneration after spinal cord injury.
Cell replacement therapy is one potential avenue for central nervous system (CNS) repair. However, transplanted stem cells may not contribute to long-term recovery of the damaged CNS unless they are engineered for functional advantage. To fine tune regenerative capabilities, we developed a human neural cell line expressing L1, a regeneration-conducive adhesion molecule, under the control of a doxycycline regulatable Tet-off promoter. ⋯ As compared to the hL1-off versus hL1-on cell transplanted mice 6 weeks post-transplantation, expression levels of L1, migration of transplanted cells, and immunoreactivity for tyrosine hydroxylase were higher, whereas expression of chondroitin sulfate proteoglycans was lower. Results indicate that L1 expression is regulatable in human stem cells by doxycycline in a nonviral engineering approach. Regulatable expression in a prospective nonleaky Tet-off system could hold promise for therapy, based on the multifunctional roles of L1, including neuronal migration and survival, neuritogenesis, myelination, and synaptic plasticity.
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Journal of neurotrauma · Mar 2014
ReviewPrehospital use of cervical collars in trauma patients - a critical review.
The cervical collar has been routinely used for trauma patients for more than 30 years and is a hallmark of state-of-the-art prehospital trauma care. However, the existing evidence for this practice is limited: Randomized, controlled trials are largely missing, and there are uncertain effects on mortality, neurological injury, and spinal stability. ⋯ In this critical review, we discuss the pros and cons of collar use in trauma patients and reflect on how we can move our clinical practice forward. Conclusively, we propose a safe, effective strategy for prehospital spinal immobilization that does not include routine use of collars.
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Journal of neurotrauma · Mar 2014
Wnts are expressed in the spinal cord of adult mice and are differentially induced after injury.
The Wnt family of proteins plays key roles during central nervous system development and has been involved in several neuropathologies during adulthood, including spinal cord injury (SCI). However, Wnts expression knowledge is relatively limited during adult stages. Here, we sought to define the Wnt family expression pattern after SCI in adult mice by using quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). ⋯ In conclusion, we demonstrate Wnt expression in the adult spinal cord of mice that is modulated by SCI, which differs from that previously described in rats. Further, Fz receptors are differentially expressed by neurons and glial cells, suggestive for cell-specific patterns and thus diverse physiological roles. Further studies will help toward in-depth characterization of the role of all Wnt factors and receptors described and eventually allow for the design of novel therapies.
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Journal of neurotrauma · Mar 2014
Characterization of Vascular Disruption and Blood-Spinal Cord Barrier Permeability Following Traumatic Spinal Cord Injury.
Significant vascular changes occur subsequent to spinal cord injury (SCI), which contribute to progressive pathophysiology. In the present study, we used female Wistar rats (300-350 g) and a 35-g clip-compression injury at T6 to T7 to characterize the spatial and temporal vascular changes that ensue post-SCI. Before sacrifice, animals were injected with vascular tracing dyes (2% Evans Blue (EB) or fluorescein isothiocyanate/Lycopersicon esculentum agglutinin [FITC-LEA]) to assess blood-spinal cord barrier (BSCB) integrity or vascular architecture, respectively. ⋯ White versus gray matter (GM) quantification showed that GM vessels are more susceptible to SCI. Finally, we observed an endogenous angiogenic response between 3 and 7 days postinjury: maximal endothelial cell proliferation was observed at day 5. These data indicate that BSCB disruption and endogenous revascularization occur at specific time points after injury, which may be important for developing effective therapeutic interventions for SCI.
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Journal of neurotrauma · Mar 2014
Valproic acid protects motor neuron death by inhibiting oxidative stress and ER stress-mediated cytochrome c release after spinal cord injury.
Both oxidative stress and endoplasmic reticulum (ER) stress are known to contribute to secondary injury, ultimately leading to cell death after spinal cord injury (SCI). Here, we showed that valproic acid (VPA) reduced cell death of motor neurons by inhibiting cytochrome c release mediated by oxidative stress and ER stress after SCI. After SCI, rats were immediately injected with VPA (300 mg/kg) subcutaneously and further injected every 12 h for an indicated time period. ⋯ On the other hand, VPA treatment inhibited ER stress-induced caspase-12 activation, which is activated in motor neurons after SCI. In addition, VPA increased the Bcl-2/Bax ratio and inhibited CHOP expression. Taken together, our results suggest that cell death of motor neurons after SCI is mediated through oxidative stress and ER stress-mediated cytochrome c release and VPA-inhibited cytochrome c release by attenuating ROS-induced JNK activation followed by Mcl-1 and Bim phosphorylation and ER stress-coupled CHOP expression.