Journal of neurotrauma
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Journal of neurotrauma · Feb 2017
Predicting recruitment feasibility for acute spinal cord injury clinical trials in Canada using national registry data.
Traumatic spinal cord injury (SCI) represents a significant burden of illness, but it is relatively uncommon and heterogeneous, making it challenging to achieve sufficient subject enrollment in clinical trials of therapeutic interventions for acute SCI. The Rick Hansen Spinal Cord Injury Registry (RHSCIR) is a national SCI Registry that enters patients with SCI from acute-care centers across Canada. To predict the feasibility of conducting clinical trials of acute SCI within Canada, we have applied the inclusion/exclusion criteria of six previously conducted SCI trials to the RHSCIR data set and generated estimates of how many Canadian persons would have been eligible theoretically for enrollment in these studies. ⋯ Projected annual numbers of eligible patients for each trial were: Minocycline, 117; Riluzole, 62; STASCIS, 109; Cethrin, 101; NOGO, 82; and Sygen, 70. An additional 8.0% of the sample had a major head injury (Glasgow Coma Scale [GCS] score ≤12) and would have been excluded from the trials. RHSCIR provides a comprehensive national data set that may serve as a useful tool in the planning of multicenter clinical SCI trials.
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Journal of neurotrauma · Feb 2017
Characterising the severity of autonomic cardiovascular dysfunction after spinal cord injury using a novel 24 hour ambulatory blood pressure analysis software.
Cardiovascular disease is one of the leading causes of morbidity and mortality in the spinal cord injury (SCI) population. SCI may disrupt autonomic cardiovascular homeostasis, which can lead to persistent hypotension, irregular diurnal rhythmicity, and the development of autonomic dysreflexia (AD). There is currently no software available to perform automated detection and evaluation of cardiovascular autonomic dysfunction(s) such as those generated from 24 h ambulatory blood pressure monitoring (ABPM) recordings in the clinical setting. ⋯ Cervical SCI presented with more frequent (p = 0.0043) and severe AD (p = 0.0343) than did high thoracic SCI. Cervical SCI exhibited higher systolic and diastolic blood pressure during the night and lower heart rate during the day than high thoracic SCI. In conclusion, our ABPM AD Detection Software was equally as effective in detecting the frequency and severity of AD and hypotensive events as manual detection, suggesting that this software can be used in the clinical setting to expedite ABPM analyses.
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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
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
AC105 Increases Extracellular Magnesium Delivery and Reduces Excitotoxic Glutamate Exposure within Injured Spinal Cords in Rats.
Magnesium (Mg2+) homeostasis is impaired following spinal cord injury (SCI) and the loss of extracellular Mg2+ contributes to secondary injury by various mechanisms, including glutamate neurotoxicity. The neuroprotective effects of high dose Mg2+ supplementation have been reported in many animal models. Recent studies found that lower Mg2+ doses also improved neurologic outcomes when Mg2+ was formulated with polyethylene glycol (PEG), suggesting that a PEG/ Mg2+ formulation might increase Mg2+ delivery to the injured spinal cord, compared with that of MgSO4 alone. ⋯ Repeated MgSO4 infusions slightly increased the Mg2+ concentrations while saline infusion had no effect. In addition, AC105 treatment significantly reduced extracellular glutamate levels in the lesion center after SCI. These results indicate that intravenous infusion of PEG-formulated Mg2+ normalized the Mg2+ homeostasis following SCI and reduced potentially neurotoxic glutamate levels, consistent with a neuroprotective mechanism of blocking excitotoxicity.