Blood-based diagnostics of traumatic brain injuries.

Banyan Biomarkers, Inc., 12085 Research Drive, Alachua, FL 32615, USA.
Expert Review of Molecular Diagnostics (Impact Factor: 4.27). 01/2011; 11(1):65-78. DOI: 10.1586/erm.10.104
Source: PubMed

ABSTRACT Traumatic brain injury is a major health and socioeconomic problem that affects all societies. However, traditional approaches to the classification of clinical severity are the subject of debate and are being supplemented with structural and functional neuroimaging, as the need for biomarkers that reflect elements of the pathogenetic process is widely recognized. Basic science research and developments in the field of proteomics have greatly advanced our knowledge of the mechanisms involved in damage and have led to the discovery and rapid detection of new biomarkers that were not available previously. However, translating this research for patients' benefits remains a challenge. In this article, we summarize new developments, current knowledge and controversies, focusing on the potential role of these biomarkers as diagnostic, prognostic and monitoring tools of brain-injured patients.


Available from: Kevin KW Wang, Apr 28, 2015
  • Article: Biomarkers.
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    ABSTRACT: Biomarkers are key tools and can provide crucial information on the complex cascade of events and molecular mechanisms underlying traumatic brain injury (TBI) pathophysiology. Obtaining a profile of distinct classes of biomarkers reflecting core pathologic mechanisms could enable us to identify and characterize the initial injury and the secondary pathologic cascades. Thus, they represent a logical adjunct to improve diagnosis, track progression and activity, guide molecularly targeted therapy, and monitor therapeutic response in TBI. Accordingly, great effort has been put into the identification of novel biomarkers in the past 25 years. However, the role of brain injury markers in clinical practice has been long debated, due to inconsistent regulatory standards and lack of reliable evidence of analytical validity and clinical utility. We present a comprehensive overview of the markers currently available while characterizing their potential role and applications in diagnosis, monitoring, drug discovery, and clinical trials in TBI. In reviewing these concepts, we discuss the recent inclusion of brain damage biomarkers in the diagnostic guidelines and provide perspectives on the validation of such markers for their use in the clinic. © 2015 Elsevier B.V. All rights reserved.
    Handbook of Clinical Neurology 01/2015; 127:245-65. DOI:10.1016/B978-0-444-52892-6.00016-7
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    ABSTRACT: The multifactorial nature of traumatic brain injury (TBI), especially the complex secondary tissue injury involving intertwined networks of molecular pathways that mediate cellular behavior, has confounded attempts to elucidate the pathology underlying the progression of TBI. Here, systems biology strategies are exploited to identify novel molecular mechanisms and protein indicators of brain injury. To this end, we performed a meta-analysis of four distinct high-throughput gene expression studies involving different animal models of TBI. By using canonical pathways and a large human protein-interaction network as a scaffold, we separately overlaid the gene expression data from each study to identify molecular signatures that were conserved across the different studies. At 24 hr after injury, the significantly activated molecular signatures were nonspecific to TBI, whereas the significantly suppressed molecular signatures were specific to the nervous system. In particular, we identified a suppressed subnetwork consisting of 58 highly interacting, coregulated proteins associated with synaptic function. We selected three proteins from this subnetwork, postsynaptic density protein 95, nitric oxide synthase 1, and disrupted in schizophrenia 1, and hypothesized that their abundance would be significantly reduced after TBI. In a penetrating ballistic-like brain injury rat model of severe TBI, Western blot analysis confirmed our hypothesis. In addition, our analysis recovered 12 previously identified protein biomarkers of TBI. The results suggest that systems biology may provide an efficient, high-yield approach to generate testable hypotheses that can be experimentally validated to identify novel mechanisms of action and molecular indicators of TBI. © 2014 Wiley Periodicals, Inc.
    Journal of Neuroscience Research 02/2015; 93(2). DOI:10.1002/jnr.23503 · 2.73 Impact Factor
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    ABSTRACT: INTRODUCTION Severe Central Nervous System (CNS) injuries, including Spinal Cord Injury (SCI), are common causes of disability resulting from trauma. In CNS injury, the important factors which determine the prognosis of patients are the severity of the primary injury (at the time of traumatic impact) and the ensuing secondary injury. Successful management of SCI also depends on accurate diagnosis of primary injury and prevention of delayed secondary injury. Recently innovations in the fi eld of biomarkers have been made; as yet there is no consensus on their clinical use for SCI. The aims of this chapter are therefore to evaluate the current status of protein biomarkers in SCI, and to discuss their potential diagnostic and prognostic value for SCI. We will also present novel biomarker data from CSF and plasma in SCI, both in animal models and patients.
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