Journal of neurotrauma
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Journal of neurotrauma · Jul 2018
Unique properties associated with the brain penetrant iron chelator HBED reveal remarkable beneficial effects after brain trauma.
Iron is postulated to contribute to secondary injury after brain trauma through various pathways including oxidative stress and inflammation. Therefore, one goal is to limit iron toxicity by either directly limiting iron activity, or limiting the secondary cascade mediated by iron, therefore rescuing the brain from damage after trauma. The N,N'-Di(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid monohydrochloride (HBED) is a unique iron chelator that has the ability to cross the intact blood-brain barrier; it has a higher affinity to iron, and it has a longer half-life than most commonly used chelators. ⋯ These effects are related to a reduction in microgliosis and oxidiative stress markers in the impacted corpus callosum area by 39.8 ± 7.3%, and by 80.5 ± 0.8% (p < 0.05), respectively. AQP4 staining is also attenuated in the hippocampus of HBED-treated mice. Therefore, our results suggest that HBED should be considered as a therapeutic tool to facilitate the recovery process following brain trauma.
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Journal of neurotrauma · Jul 2018
Prehospital Trauma Care among 68 European Neurotrauma Centers: Results of the CENTER-TBI Provider Profiling Questionnaires.
The first hour following traumatic brain injury (TBI) is considered crucial to prevent death and disability. It is, however, not established yet how the prehospital care should be organized to optimize recovery during the first hour. The objective of the current study was to examine variation in prehospital trauma care across Europe aiming to inform comparative effectiveness analyses on care for neurotrauma patients. ⋯ We found wide variation in prehospital trauma care across Europe. This may reflect differences in socio-economic situations, geographic differences, and a general lack of strong evidence for some aspects of prehospital care. The current variation provides the opportunity to study the effectiveness of prehospital interventions and systems of care in comparative effectiveness research.
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Journal of neurotrauma · Jul 2018
Neuroprotective Effects of Cyclosporine in a Porcine Pre-Clinical Trial of Focal Traumatic Brain Injury.
Mitochondrial dysfunction is thought to be a hallmark of traumatic brain injury (TBI) and plays a pivotal role in the resulting cellular injury. Cyclophilin D-mediated activation of the mitochondrial permeability transition pore has been suggested to contribute to this secondary injury cascade. Cyclosporine possesses neuroprotective properties that have been attributed to the desensitization of mitochondrial permeability transition pore activation. ⋯ Cyclosporine reduced the volume of parenchymal injury by 35%, as well as improved markers of neuronal injury, as measured with magnetic resonance spectroscopic imaging. Further, a consistent trend toward positive improvements in brain metabolism and mitochondrial function was observed in the pericontusional tissue. In this study, we have demonstrated efficacy using a novel cyclosporine formulation in clinically relevant and translatable outcome metrics in a large animal model of focal TBI.
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Journal of neurotrauma · Jul 2018
Performance Evaluation of a Multiplex Assay for Simultaneous Detection of Four Clinically Relevant Traumatic Brain Injury Biomarkers.
Traumatic brain injury (TBI) results in heterogeneous pathology affecting multiple cells and tissue types in the brain. It is likely that assessment of such complexity will require simultaneous measurement of multiple molecular biomarkers in a single sample of biological fluid. We measured glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1), neurofilament light chain (NF-L) and total tau in plasma samples obtained from 107 subjects enrolled in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) Study using the Quanterix Simoa 4-Plex assay. ⋯ The weakest correlation was between the glial marker GFAP and the axonal marker tau (coefficient = 0.06). The areas under the curves for distinguishing between subjects with/without abnormal head CT for multiplex GFAP, UCH-L1, NF-L, and total tau were: 0.88 (95% confidence interval 0.81-0.95), 0.86 (0.79-0.93), 0.84 (0.77-0.92), and 0.77 0.67-0.86), respectively. We conclude that the multiplex assay provides simultaneous quantification of GFAP, UCH-L1, NF-L, and tau, and may be clinically useful in the diagnosis of TBI as well as identifying different types of cellular injury.
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Journal of neurotrauma · Jul 2018
Corpus Callosum Vasculature Predicts White Matter Microstructure Abnormalities after Pediatric Mild Traumatic Brain Injury.
Emerging data suggest that pediatric traumatic brain injury (TBI) is associated with impaired developmental plasticity and poorer neuropsychological outcomes than adults with similar head injuries. Unlike adult mild TBI (mTBI), the effects of mTBI on white matter (WM) microstructure and vascular supply are not well understood in the pediatric population. The cerebral vasculature plays an important role providing necessary nutrients and removing waste. ⋯ However, vascular features of the ipsilateral CC such as vessel density, length, and number of junctions were persistently altered following mTBI. Correlative analysis showed a strong inverse relationship between ADC and vessel density at 60 DPI, suggesting increased vessel density following mTBI may restrict WM diffusion characteristics. Our findings suggest that WM vasculature contributes to the long-term microstructural changes within the ipsilateral CC following mTBI.