Journal of neurotrauma
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Journal of neurotrauma · Feb 2017
Spinal Cord Transcriptomic and Metabolomic Analysis after Excitotoxic Injection Injury Model of Syringomyelia.
Syringomyelia is a condition of the spinal cord in which a syrinx, or fluid-filled cavity, forms from trauma, malformation, or general disorder. Previous work has shown that in noncanalicular syringomyelia irregular flow and pressure conditions enhance the volumetric growth of syrinxes. A better understanding of the underlying molecular pathways associated with syrinx formation will unveil targets for treatments and possibly prevention of syringomyelia in the future. ⋯ Although transcriptional changes indicated gliosis and loss of neurons, no neuropathic pain was detected by von Frey allodynia testing. Unique transporters were revealed to be highly dysregulated, including significant increases in betaine/glycine transporter (BGT-1), K+/Cl- co-transporter (KCC4), and aquaporin 1 (AQP1), along with the upregulation of small molecule osmolytes taurine and betaine. The identified metabolites are of particular interest because of their involvement in osmotic homeostasis and need to be investigated further for their specific involvement in trauma-induced syrinxes.
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Journal of neurotrauma · Feb 2017
A Morphological and Molecular Characterization of the Spinal Cord Following Ventral Root Avulsion or Distal Peripheral Nerve Axotomy Injuries in Adult Rats.
Retrograde cell death in sensory dorsal root ganglion cells following peripheral nerve injury is well established. However, available data regarding the underlying mechanism behind injury induced motoneuron death are conflicting. By comparing morphological and molecular changes in spinal motoneurons after L4-L5 ventral root avulsion (VRA) and distal peripheral nerve axotomy (PNA) 7 and 14 days postoperatively, we aimed to gain more insight about the mechanism behind injury-induced motoneuron degeneration. ⋯ Moreover, the altered gene expression correlated with protein changes. These results show that the spinal motoneurons reacted in a similar fashion with respect to morphological changes after both proximal and distal injury. However, the increased expression of caspase-3, caspase-8, and related death receptors after VRA suggest that injury- induced motoneuron degeneration is mediated through an apoptotic mechanism, which might involve both the intrinsic and the extrinsic pathways.
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Journal of neurotrauma · Feb 2017
Disruption of locomotion in response to hindlimb muscle stretch at acute and chronic time points after a spinal cord injury in rats.
After spinal cord injury (SCI) muscle contractures develop in the plegic limbs of many patients. Physical therapists commonly use stretching as an approach to avoid contractures and to maintain the extensibility of soft tissues. We found previously that a daily stretching protocol has a negative effect on locomotor recovery in rats with mild thoracic SCI. ⋯ The current study extends our observations of the stretching phenomenon to a more clinically relevant moderately severe SCI animal model. The results are in agreement with our previous findings and further demonstrate that spinal cord locomotor circuitry is especially vulnerable to the negative effects of stretching at chronic time points. While the clinical relevance of this phenomenon remains unknown, we speculate that stretching may contribute to the lack of locomotor recovery in some patients.
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Journal of neurotrauma · Feb 2017
Heme oxygenase-1 inhibits neuronal apoptosis in spinal cord injury through down-regulation of Cdc42-MLK3-MKK7-JNK3 axis.
The mechanism by which spinal cord injury (SCI) induces neuronal death has not been thoroughly understood. Investigation on the molecular signal pathways involved in SCI-mediated neuronal apoptosis is important for development of new therapeutics for SCI. In the current study, we explore the role of heme oxygenase-1 (HO-1) in the modulation of mixed lineage kinase 3/mitogen-activated protein kinase kinase/cJUN N-terminal kinase 3 (MLK3/MKK7/JNK3) signaling, which is a pro-apoptotic pathway, after SCI. ⋯ In vitro experiments indicated that Cdc42 was essential for neuronal apoptosis, while transduction of neurons with HO-1-expressing adeno-associated virus significantly reduced neuronal apoptosis to enhance neuronal survival. Therefore, our study disclosed a novel mechanism by which HO-1 exerted its neuroprotective efficacy. Our discovery might be valuable for developing a new therapeutic approach for SCI.
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Journal of neurotrauma · Feb 2017
Vagal control of breathing pattern following mid-cervical contusion in rats.
The present study was designed to establish a midcervical contusion model that can simulate long-term respiratory deficits, and investigate the breathing pattern during vagal-mediated respiratory reflexes following midcervical contusion. Moderate and severe (impactor height: 6.25 or 12.5 mm) contusion was induced at midline C3-4 spinal cord in adult Sprague-Dawley rats. The ventilatory behaviors of unanesthetized were evaluated by whole body plethysmography at 1 day and 1, 2, 4, and 8 weeks post-injury. ⋯ Increased positive end-expired pressure also caused an increase in the expiratory duration in uninjured and moderately contused animals; however, severely contused animals exhibited an attenuated response. At 2 and 8 weeks post-injury, both the pulmonary chemoreflex and the Hering-Breuer inflation reflex were similar between uninjured and contused animals. These data suggested that midcervical contusion can cause a long-term respiratory impairment and a transiently attenuation of vagal-mediated respiratory reflexes.