Journal of neurotrauma
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Journal of neurotrauma · Sep 2013
Randomized Controlled Trial Multicenter StudyExposure of cyclosporin a in whole blood, cerebral spinal fluid, and brain extracellular fluid dialysate in adults with traumatic brain injury.
Cyclosporin A (CsA), an immunosuppressive medication traditionally used in the prevention of post-transplant rejection, is a promising neuroprotective agent for traumatic brain injury (TBI). Preliminary studies in animals and humans describe the efficacy and safety of CsA when administered following neurotrauma. The objective of this study is to describe CsA exposure in adults with severe TBI by assessing concentrations in whole blood, cerebrospinal fluid (CSF), and brain extracellular fluid (ECF) dialysate as measured by brain microdialysis. ⋯ CsA was detected in the blood, CSF, and brain ECF dialysate. CsA exposure characteristic differences exist for whole blood, CSF, and ECF dialysate in severe TBI patients when administered as a continuous intravenous infusion. These exposure characteristics should be used for safer CsA dose optimization to achieve target CsA concentrations for neuroprotection in future TBI studies.
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Traumatic brain injuries (TBI) impose a significant burden on the health care system. The aim of the current study was to explore variation in costs in a group of rehabilitation patients in Victoria, Australia, following complicated mild-to-severe TBI treated under the accident compensation system administered by the Transport Accident Commission. Study participants included 1237 individuals with mild-to-severe TBI recruited consecutively from a TBI rehabilitation program. ⋯ Higher hospital and medical costs were associated with these factors, but also with other physical injuries, lower education, pre-injury unemployment, living outside the city, speaking English at home, and, in the case of medical costs, older age and having had pre-injury psychiatric treatment. Higher paramedical costs were associated with most of these variables, but also with being employed prior to injury and being female. In line with the multifaceted nature of TBI, the current findings suggest that both injury-related and demographic factors determine costs following injury.
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Journal of neurotrauma · Sep 2013
17β-estradiol confers protection after traumatic brain injury in the rat and involves activation of g protein-coupled estrogen receptor 1.
Abstract Traumatic brain injury (TBI) is a significant public health problem in the United States. Despite preclinical success of various drugs, to date all clinical trials investigating potential therapeutics have failed. Recently, sex steroid hormones have sparked interest as possible neuroprotective agents after traumatic injury. ⋯ We also report a significant reduction in astrogliosis in the ipsilateral cortex, hilus, and CA 2/3 region of the hippocampus. Finally, these effects were observed to be chiefly dose-dependent for E2, with the 5 mg/kg dose generating a more robust level of protection. Our findings further elucidate estrogenic compounds as a clinically relevant pharmacotherapeutic strategy for treatment of secondary injury following TBI, and intriguingly, reveal a novel potential therapeutic target in GPER.
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Journal of neurotrauma · Sep 2013
Why Is CA3 More Vulnerable Than CA1 in Experimental Models of Controlled Cortical Impact-Induced Brain Injury?
One interesting finding of controlled cortical impact (CCI) experiments is that the CA3 region of the hippocampus, which is positioned further from the impact than the CA1 region, is reported as being more injured. The current literature has suggested a positive correlation between brain tissue stretch and neuronal cell loss. However, it is counterintuitive to assume that CA3 is stretched more during CCI injury. ⋯ Simulation results demonstrated that for CCI with a 5-mm diameter, flat shape impactor, CA3 experienced increased tensile strains over a larger area and to a greater magnitude than did CA1 for group 1, which best explained why CA3 is more sensitive to CCI injury. However, for groups 2-4, the total volume with high strain (>30%) in CA3 was smaller than that in CA1. The FE rat brain model, with detailed hippocampal structures presented here, will help to engineer desired experimental neurotrauma models by virtually characterizing brain biomechanics before testing.
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Journal of neurotrauma · Sep 2013
Dose- and Time-Dependent Neuroprotective Effects of Pycnogenol(®) following Traumatic Brain Injury.
After traumatic brain injury (TBI), both primary and secondary injury cascades are initiated, leading to neuronal death and cognitive dysfunction. We have previously shown that the combinational bioflavonoid, Pycnogenol (PYC), alters some secondary injury cascades and protects synaptic proteins when administered immediately following trauma. The purpose of the present study was to explore further the beneficial effects of PYC and to test whether it can be used in a more clinically relevant fashion. ⋯ PYC treatment significantly protected both the cortex and hippocampus from injury-related declines in pre- and post-synaptic proteins. These results demonstrate that a single i.v. treatment of PYC is neuroprotective after TBI with a therapeutic window of at least 4 h post trauma. The natural bioflavonoid PYC may provide a possible therapeutic intervention in neurotrauma.