Frontiers in neurology
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Frontiers in neurology · Jan 2015
ReviewBench-to-Bedside and Bedside Back to the Bench; Seeking a Better Understanding of the Acute Pathophysiological Process in Severe Traumatic Brain Injury.
Despite substantial investments, traumatic brain injury (TBI) remains one of the major disorders that lack specific pharmacotherapy. To a substantial degree, this situation is due to lack of understanding of the pathophysiological process of the disease. ⋯ The pathophysiology during the acute phase of severe TBI is especially poorly understood. In this Mini review, I discuss some of the incongruences between current clinical practices and needs versus information provided by experimental TBI research as well as the benefits of designing animal experiments with translation into clinical practice in mind.
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Frontiers in neurology · Jan 2015
Multivariate analysis of traumatic brain injury: development of an assessment score.
Important challenges for the diagnosis and monitoring of mild traumatic brain injury (mTBI) include the development of plasma biomarkers for assessing neurologic injury, monitoring pathogenesis, and predicting vulnerability for the development of untoward neurologic outcomes. While several biomarker proteins have shown promise in this regard, used individually, these candidates lack adequate sensitivity and/or specificity for making a definitive diagnosis or identifying those at risk of subsequent pathology. The objective for this study was to evaluate a panel of six recognized and novel biomarker candidates for the assessment of TBI in adult patients. ⋯ The combined fold-changes in plasma levels of PRDX6, S100b, MCP1, NSE, and BDNF resulted in the formulation of a TBI assessment score that identified mTBI with a receiver operating characteristic (ROC) area under the curve of 0.97, when compared to healthy controls. This research demonstrates that a profile of biomarker responses can be used to formulate a diagnostic score that is sensitive for the detection of mTBI. Ideally, this multivariate assessment strategy will be refined with additional biomarkers that can effectively assess the spectrum of TBI and identify those at particular risk for developing neuropathologies as consequence of a mTBI event.
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Frontiers in neurology · Jan 2015
The Temporal Pattern of Changes in Serum Biomarker Levels Reveals Complex and Dynamically Changing Pathologies after Exposure to a Single Low-Intensity Blast in Mice.
Time-dependent changes in blood-based protein biomarkers can help identify the -pathological processes in blast-induced traumatic brain injury (bTBI), assess injury severity, and monitor disease progression. We obtained blood from control and injured mice (exposed to a single, low-intensity blast) at 2-h, 1-day, 1-week, and 1-month post-injury. We then determined the serum levels of biomarkers related to metabolism (4-HNE, HIF-1α, ceruloplasmin), vascular function (AQP1, AQP4, VEGF, vWF, Flk-1), inflammation (OPN, CINC1, fibrinogen, MIP-1a, OX-44, p38, MMP-8, MCP-1 CCR5, CRP, galectin-1), cell adhesion and the extracellular matrix (integrin α6, TIMP1, TIMP4, Ncad, connexin-43), and axonal (NF-H, Tau), neuronal (NSE, CK-BB) and glial damage (GFAP, S100β, MBP) at various post-injury time points. ⋯ Conversely, serum levels of the majority of biomarkers related to metabolic and vascular functions, cell adhesion, as well as neuronal and axonal damage remained elevated at the termination of the experiment (1 month), indicating long-term systemic and cerebral alterations due to blast. Our findings show that the exposure to a single, low-intensity blast induces complex pathological processes with distinct temporal profiles. Hence, monitoring serum biomarker levels at various post-injury time points may provide enhanced diagnostics in blast-related neurological and multi-system deficits.
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Frontiers in neurology · Jan 2015
Effects of blast overpressure on neurons and glial cells in rat organotypic hippocampal slice cultures.
Due to recent involvement in military conflicts, and an increase in the use of explosives, there has been an escalation in the incidence of blast-induced traumatic brain injury (bTBI) among US military personnel. Having a better understanding of the cellular and molecular cascade of events in bTBI is prerequisite for the development of an effective therapy that currently is unavailable. The present study utilized organotypic hippocampal slice cultures (OHCs) exposed to blast overpressures of 150 kPa (low) and 280 kPa (high) as an in vitro bTBI model. ⋯ Labeling OHCs with PI, neuronal, and glial markers revealed that the blast-evoked extensive neuronal death and to a lesser extent loss of glial cells. Furthermore, our data demonstrated activation of astrocytes and microglial cells in low- and high-blasted OHCs, which reached a statistically significant difference in the high-blast group. These data confirmed that our in vitro bTBI model is a useful tool for studying cellular and molecular changes after blast exposure.