Frontiers in neurology
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Frontiers in neurology · Jan 2015
ReviewSystemic, local, and imaging biomarkers of brain injury: more needed, and better use of those already established?
Much progress has been made over the past two decades in the treatment of severe acute brain injury, including traumatic brain injury and subarachnoid hemorrhage, resulting in a higher proportion of patients surviving with better outcomes. This has arisen from a combination of factors. These include improvements in procedures at the scene (pre-hospital) and in the hospital emergency department, advances in neuromonitoring in the intensive care unit, both continuously at the bedside and intermittently in scans, evolution and refinement of protocol-driven therapy for better management of patients, and advances in surgical procedures and rehabilitation. ⋯ Large Phase III studies of clinical outcomes are costly, consuming time and resources. It is therefore important that adequate Phase II clinical studies with informative surrogate endpoints are performed employing appropriate biomarkers. In this article, we review some of the available systemic, local, and imaging biomarkers and technologies relevant in acute brain injury patients, and highlight gaps in the current state of knowledge.
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Frontiers in neurology · Jan 2015
ReviewVascular and inflammatory factors in the pathophysiology of blast-induced brain injury.
Blast-related traumatic brain injury (TBI) has received much recent attention because of its frequency in the conflicts in Iraq and Afghanistan. This renewed interest has led to a rapid expansion of clinical and animal studies related to blast. In humans, high-level blast exposure is associated with a prominent hemorrhagic component. ⋯ At low levels of blast exposure, a microvascular pathology has been observed in the presence of an otherwise normal brain parenchyma, suggesting that the vasculature may be selectively vulnerable to blast injury. Chronic immune activation in brain following vascular injury may lead to neurobehavioral changes in the absence of direct neuronal pathology. Strategies aimed at preventing or reversing vascular damage or modulating the immune response may improve the chronic neuropsychiatric symptoms associated with blast-related TBI.
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Frontiers in neurology · Jan 2015
ReviewRole of the Contralesional Hemisphere in Post-Stroke Recovery of Upper Extremity Motor Function.
Identification of optimal treatment strategies to improve recovery is limited by the incomplete understanding of the neurobiological principles of recovery. Motor cortex (M1) reorganization of the lesioned hemisphere (ipsilesional M1) plays a major role in post-stroke motor recovery and is a primary target for rehabilitation therapy. Reorganization of M1 in the hemisphere contralateral to the stroke (contralesional M1) may, however, serve as an additional source of cortical reorganization and related recovery. ⋯ Decreasing contralesional M1 excitability in these patients may result in deterioration of paretic limb performance. In animal stroke models, reorganizational changes in contralesional M1 depend on the lesion size and rehabilitation treatment and include long-term changes in neurotransmitter systems, dendritic growth, and synapse formation. While there is, therefore, some evidence that activity in contralesional M1 will impact the extent of motor function of the paretic limb in the subacute and chronic phase post-stroke and may serve as a new target for rehabilitation treatment strategies, the precise factors that specifically influence its role in the recovery process remain to be defined.
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Frontiers in neurology · Jan 2015
ReviewThe Complexity of Biomechanics Causing Primary Blast-Induced Traumatic Brain Injury: A Review of Potential Mechanisms.
Primary blast-induced traumatic brain injury (bTBI) is a prevalent battlefield injury in recent conflicts, yet biomechanical mechanisms of bTBI remain unclear. Elucidating specific biomechanical mechanisms is essential to developing animal models for testing candidate therapies and for improving protective equipment. Three hypothetical mechanisms of primary bTBI have received the most attention. ⋯ These three mechanisms may not be mutually exclusive, and quantifying exposure thresholds (for blasts of a given duration) is essential for determining which mechanisms may be contributing for a level of blast exposure. Progress has been hindered by experimental designs, which do not effectively expose animal models to a single mechanism and by over-reliance on poorly validated computational models. The path forward should be predictive validation of computational models by quantitative confirmation with blast experiments in animal models, human cadavers, and biofidelic human surrogates over a range of relevant blast magnitudes and durations coupled with experimental designs, which isolate a single injury mechanism.
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Frontiers in neurology · Jan 2015
ReviewAutosomal Dominant Alzheimer Disease: A Unique Resource to Study CSF Biomarker Changes in Preclinical AD.
Our understanding of the pathogenesis of Alzheimer disease (AD) has been greatly influenced by investigation of rare families with autosomal dominant mutations that cause early onset AD. Mutations in the genes coding for amyloid precursor protein (APP), presenilin 1 (PSEN-1), and presenilin 2 (PSEN-2) cause over-production of the amyloid-β peptide (Aβ) leading to early deposition of Aβ in the brain, which in turn is hypothesized to initiate a cascade of processes, resulting in neuronal death, cognitive decline, and eventual dementia. ⋯ Herein, we review the literature on CSF biomarkers in autosomal dominant AD (ADAD), which has contributed to a detailed road map of AD pathogenesis, especially during the preclinical period, prior to the appearance of any cognitive symptoms. Current drug trials are also taking advantage of the unique characteristics of ADAD and utilizing CSF biomarkers to accelerate development of effective therapies for AD.