Articles: traumatic-brain-injuries.
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Review
Epileptogenesis following experimentally induced traumatic brain injury - a systematic review.
Traumatic brain injury (TBI) is a complex neurotrauma in civilian life and the battlefield with a broad spectrum of symptoms, long-term neuropsychological disability, as well as mortality worldwide. Posttraumatic epilepsy (PTE) is a common outcome of TBI with unknown mechanisms, followed by posttraumatic epileptogenesis. There are numerous rodent models of TBI available with varying pathomechanisms of head injury similar to human TBI, but there is no evidence for an adequate TBI model that can properly mimic all aspects of clinical TBI and the first successive spontaneous focal seizures follow a single episode of neurotrauma with respect to epileptogenesis. ⋯ Mossy fiber sprouting, loss of dentate hilar neurons along with recurrent seizures, and epileptic discharge similar to human PTE have been studied in fluid percussion injury, weight-drop injury, and cortical impact models, but further refinement of animal models and functional test is warranted to better understand the underlying pathophysiology of posttraumatic epileptogenesis. A multifaceted research approach in TBI model may lead to exploration of the potential treatment measures, which are a major challenge to the research community and drug developers. With respect to clinical setting, proper patient data collection, improved clinical trials with advancement in drug delivery strategies, blood-brain barrier permeability, and proper monitoring of level and effects of target drug are also important.
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Journal of neurotrauma · Mar 2016
ReviewSynthesis of Findings, Current Investigations, and Future Directions: Operation Brain Trauma Therapy.
Operation Brain Trauma Therapy (OBTT) is a fully operational, rigorous, and productive multicenter, pre-clinical drug and circulating biomarker screening consortium for the field of traumatic brain injury (TBI). In this article, we synthesize the findings from the first five therapies tested by OBTT and discuss both the current work that is ongoing and potential future directions. Based on the results generated from the first five therapies tested within the exacting approach used by OBTT, four (nicotinamide, erythropoietin, cyclosporine A, and simvastatin) performed below or well below what was expected based on the published literature. ⋯ The sixth and seventh therapies have just completed testing (glibenclamide and Kollidon VA 64), and an eighth drug (AER 271) is in testing. Incorporation of circulating brain injury biomarker assessments into these pre-clinical studies suggests considerable potential for diagnostic and theranostic utility of glial fibrillary acidic protein in pre-clinical studies. Given the failures in clinical translation of therapies in TBI, rigorous multicenter, pre-clinical approaches to therapeutic screening such as OBTT may be important for the ultimate translation of therapies to the human condition.
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Journal of neurotrauma · Mar 2016
ReviewOperation Brain Trauma Therapy: Approach to Modeling, Therapy Evaluation, Drug Selection, and Biomarker Assessments, for a Multi-Center Pre-Clinical Drug Screening Consortium for Acute Therapies in Severe Traumatic Brain Injury.
Traumatic brain injury (TBI) was the signature injury in both the Iraq and Afghan wars and the magnitude of its importance in the civilian setting is finally being recognized. Given the scope of the problem, new therapies are needed across the continuum of care. Few therapies have been shown to be successful. ⋯ To address this possibility and attempt to bring the most promising therapies to clinical trials, we developed Operation Brain Trauma Therapy (OBTT), a multicenter, pre-clinical drug screening consortium for acute therapies in severe TBI. OBTT was developed to include a spectrum of established TBI models at experienced centers and assess the effect of promising therapies on both conventional outcomes and serum biomarker levels. In this review, we outline the approach to TBI modeling, evaluation of therapies, drug selection, and biomarker assessments for OBTT, and provide a framework for reports in this issue on the first five therapies evaluated by the consortium.
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Abnormal movements are frequently encountered in patients with brain injury hospitalized in intensive care units (ICUs), yet characterization of these movements and their underlying pathophysiology is difficult due to the comatose or uncooperative state of the patient. In addition, the available diagnostic approaches are largely derived from outpatients with neurodegenerative or developmental disorders frequently encountered in the outpatient setting, thereby limiting the applicability to inpatients with acute brain injuries. Thus, we reviewed the available literature regarding abnormal movements encountered in acutely ill patients with brain injuries. ⋯ This model seeks to classify observed abnormal movements in light of various patient-specific factors. It begins with classifying the patient's level of consciousness. Then, it integrates the frequency and type of each movement with the availability of ancillary diagnostic tests and the specific etiology of brain injury.
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Advances in technology have resulted in a plethora of invasive neuromonitoring options for practitioners to manage while caring for the complex needs of the critical care patient. Although many types of invasive neuromonitoring are available to the practitioner, intraparenchymal monitors and external ventricular devices are used most frequently in the clinical setting and are the focus of this article. In addition, multimodality monitoring has been noted to confer a survival benefit in patients with this complex type of invasive neuromonitoring and is discussed as well.