About this Research Topic

Background

Traumatic brain injury (TBI), a major and growing public health problem, appears to result not only from primary injury but also from a complex interplay among inflammatory, biochemical neurohormonal changes as well as genetic components acting on brain tissue. Emerging data suggest that an increasing number of biologic substances, referred to as biomarkers, can provided unprecedented opportunities for detecting and classifying injury and identifying pathophysiologic mechanisms and therapeutic targets.
In this Research Topic, we will include an outline of novel approaches that provide an infrastructure for discovery and validation of new biomarkers of acute brain injury. Approaches to validation can be also applied to existing biomarkers of brain injury in order to provide more rigorous assessment of their clinical utility. Importantly, there are currently no biomarkers of brain injury approved by Food and Drug Administration (FDA).
The Research Topic will include a review of proteomics techniques applied for the first time to discovery of biomarkers of central nervous system (CNS). These techniques include refined mass spectrometry technology and high throughput immunoblot techniques. Output from these approaches can identify potential candidate biomarkers employing systems biology and data mining methods that will also be described.
Once potential biomarkers have been identified, it is important to provide information on their clinical utility for diagnosis, management and prognosis of patients exposed to brain injuries. The Research Topic will include a review of both preclinical and clinical methods for biomarker validation. Preclinical models discussed include rodent models of closed head injury such as the controlled cortical impact (CCI) device. Consideration will also be given to the design and results from human clinical trials validating biomarkers of mild, moderate and severe traumatic brain injury (TBI). Human studies will include detailed analyses of the biokinetics of different biomarkers in order to understand their utility in acute, subacute and chronic phases of TBI. Consideration will also be given to relationships between levels of biomarkers and magnitude of acute injury, CT imaging profiles, occurrence of secondary insults and long term outcome.
To achieve practical clinical utility, it is important to develop highly sensitive and specific assays for individual biomarkers. Enzyme-linked immunosorbent assays (ELISAs) are the current choice for clinical use, since this assay technology provides reliable, quantitative and accurate data. ELISA technologies relevant to biomarker measurement will be discussed. In addition, The Research Topic will include an overview of developing technologies allowing concurrent assessment of multiple biomarkers (multiplex).
To date, studies of biomarkers for brain injury have been restricted to research applications only. Although there is broad recognition of clinical utility of biomarkers, the FDA has yet to approve any biomarkers of CNS injury of disease. Consideration will also be given to regulatory requirements necessary for a biomarker to file for approval by FDA.
Finally, suggestions will be provided for the way forward, with an emphasis on need to integrate traditional approaches to the classification of TBI, including structural and functional neuroimaging, and biomarker to develop best clinical practice guidelines.

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