Journal of neurotrauma
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Journal of neurotrauma · Feb 2018
Incidence and natural progression of neurogenic shock following traumatic spinal cord injury.
Neurogenic shock, a distributive type of circulatory shock after spinal cord injury (SCI), results in profound hypotension. The consequent hemodynamic instability complicates clinical management, delays surgical intervention, and impacts neurological outcome. Moreover, the reported incidence of this condition varies significantly. ⋯ By using a novel combination of hemodynamic and laboratory criteria to define neurogenic shock, the calculated incidence (29% cervical SCI) in our sample most appropriately reflects the true incidence, finding that hypovolemia was the primary factor responsible for the inconsistency in incidence reports between studies. In addition, we found a characteristic decline in blood pressure after the first week post-injury and that fluid management is not currently an integral aspect of clinical management (all persons were treated at a net fluid intake ≤ zero). The results demonstrate the need for accurate identification of neurogenic shock through consistent and appropriate criteria, which is not only important from a clinical point of view, but also in establishing accurate epidemiology to responsibly allocate resources to its management.
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Journal of neurotrauma · Feb 2018
Reduced Field of View Diffusion Tensor Imaging and Fiber Tractography of the Pediatric Cervical and Thoracic Spinal Cord Injury.
The aim of this study is to assess the utility and effectiveness of diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) of the entire pediatric cervical and thoracic spinal cord toward discrimination of typically developing (TD) controls and subjects with spinal cord injury (SCI). A total of 43 pediatric subjects, including 23 TD subjects ranging in age from 6 to 16 years old and 20 subjects with SCI ranging in age from 7 to 16 years, were recruited and scanned using a 3.0 Tesla magnetic resonance scanner. Reduced field of view diffusion tensor images were acquired axially to cover the entire spinal cord across two slabs. ⋯ An identical trend was observed in the cervical region for patients with thoracic SCI as well. When comparing TD and SCI subjects, FA and tract density were the most sensitive parameters in detecting functional changes of the spinal cord in chronic pediatric SCI. The results show that both DTI and DTT have the potential to be imaging biomarkers in the diagnosis of SCI.
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Journal of neurotrauma · Feb 2018
Facilitators and Barriers to International Collaboration in Spinal Cord Injury: Results from a Survey of Clinicians and Researchers.
International collaboration in spinal cord injury (SCI) research is necessary to overcome the challenges often encountered by clinicians and researchers, including participant recruitment, high cost, and the need for specialized expertise. However, international collaboration poses its own obstacles. The objective of this study was to conduct an international online survey to assess barriers and facilitators to international SCI clinical research, potential initiatives to facilitate future collaborations, and the use of SCI-specific data sets and standards. ⋯ The International Standards for Neurological Classification of SCI were used by 69% of participants, the International Standards to document remaining Autonomic Function after SCI by 13% of participants, and the International SCI Data Sets by 45% of participants. As the need for international collaborations in SCI research increases, it is important to identify how clinicians and researchers can be supported by SCI consumer and professional organizations, funders, and networks. Furthermore, unique solutions to overcome modifiable barriers and creation of new facilitators are also needed.
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Journal of neurotrauma · Feb 2018
ATF6α deletion modulates the ER stress response after spinal cord injury but does not affect locomotor recovery.
The endoplasmic reticulum stress response (ERSR) is activated in a variety of neurodegenerative diseases and/or traumatic injuries. Subsequent restoration of ER homeostasis may contribute to improvement in the functional outcome of these diseases. We recently demonstrated improvements in hindlimb locomotion after thoracic spinal cord injury (SCI) and implicated oligodendrocyte survival as a potential mechanism using genetic and pharmacological inhibition of the protein kinase ribonucleic acid-like ER kinase- CCAAT/enhancer binding homologous protein (PERK-CHOP) arm of the ERSR. ⋯ In contrast to what was seen after attenuation of PERK-CHOP signaling, genetic ablation of ATF6 results in modulation of ERSR and decreased survival in oligodendrocyte precursor cells against ER stress. Further, ATF6 loss delays the ERSR after SCI, potentiates PERK-ATF4-CHOP signaling and fails to improve locomotor deficits. These data suggest that deleting ATF6 levels is unlikely to be a viable therapeutic target to improve functional recovery after SCI.
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Journal of neurotrauma · Feb 2018
Rolipram-loaded polymeric micelle nanoparticle reduces secondary injury after rat compression spinal cord injury.
Among the complex pathophysiological events following spinal cord injury (SCI), one of the most important molecular level consequences is a dramatic reduction in neuronal cyclic adenosine monophosphate (cAMP) levels. Many studies shown that rolipram (Rm), a phosphodiesterase IV inhibitor, can protect against secondary cell death, reduce inflammatory cytokine levels and immune cell infiltration, and increase white matter sparing and functional improvement. Previously, we developed a polymeric micelle nanoparticle, poly(lactide-co-glycolide)-graft-polyethylenimine (PgP), for combinatorial delivery of therapeutic nucleic acids and drugs for SCI repair. ⋯ After intraspinal injection, 1,1'-dioctadecyl-3,3,3',3'-tetramethyl indotricarbocyanine Iodide-loaded PgP micelles were retained at the injection site for up to 5 days. Finally, we show that a single injection of Rm-PgP nanoparticles restored cAMP in the SCI lesion site and reduced apoptosis and the inflammatory response. These results suggest that PgP may offer an efficient and translational approach to delivering Rm as a neuroprotectant following SCI.