Journal of neurotrauma
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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.
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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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Journal of neurotrauma · Sep 2013
Multicenter Study Clinical TrialGFAP-BDP as an Acute Diagnostic Marker in Traumatic Brain Injury: Results from the Prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study.
Reliable diagnosis of traumatic brain injury (TBI) is a major public health need. Glial fibrillary acidic protein (GFAP) is expressed in the central nervous system, and breakdown products (GFAP-BDP) are released following parenchymal brain injury. Here, we evaluate the diagnostic accuracy of elevated levels of plasma GFAP-BDP in TBI. ⋯ GFAP-BDP levels reliably distinguish the presence and severity of CT scan findings in TBI patients. Although these findings confirm and extend prior studies, a larger prospective trial is still needed to validate the use of GFAP-BDP as a routine diagnostic biomarker for patient care and clinical research. The term "mild" continues to be a misnomer for this patient population, and underscores the need for evolving classification strategies for TBI targeted therapy. (ClinicalTrials.gov number NCT01565551; NIH Grant 1RC2 NS069409).
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Journal of neurotrauma · Sep 2013
Rehabilitation outcome of unconscious traumatic brain injury patients.
Outcome prediction of traumatic brain injury (TBI) patients with severe disorders of consciousness (DOC) at the end of their time in an intensive care setting is important for clinical decision making and counseling of relatives, and constitutes a major challenge. Even the question of what constitutes an improved outcome is controversially discussed. We have conducted a retrospective cohort study for the rehabilitation dynamics and outcome of TBI patients with DOC. ⋯ In conclusion, despite a strong negative selection, a substantial proportion of severe TBI patients with DOC achieve functional improvements or at least emerge from MCS within the inpatient rehabilitation phase. In order to avoid self-fulfilling prophecies in decision making, it is important to be aware of the fact that the beginning of clinical improvement may take several months after brain injury. In this study, separation of both of the functional outcome groups started by 7 weeks post-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.