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Review
, 11 (1), 65-78

Blood-based Diagnostics of Traumatic Brain Injuries

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Review

Blood-based Diagnostics of Traumatic Brain Injuries

Stefania Mondello et al. Expert Rev Mol Diagn.

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.

Figures

Figure 1
Figure 1. `The silent epidemic'
(A) Average annual numbers of brain injury-related emergency department visits, hospitalizations and deaths by external causes. (B) Percentage of average annual traumatic brain injury-related emergency department visits, hospitalizations and deaths by external causes. Motor vehicle accidents were the leading cause of traumatic brain injury (50%), followed by falls (21%) and assaults (12%).
Figure 2
Figure 2. Brain-injury biomarker genesis, distribution and temporal profile as detected in blood
(A) Paradigm for brain-injury biomarker studies. (B) Traumatic brain-injury biomarkers show a distinct temporal profile (trendline analysis). BBB: Blood–brain barrier; BDP: Breakdown product; CSF: Cerebrospinal fluid; H: Hours.
Figure 3
Figure 3. Proteomics-based biomarker discovery
CCI: Controlled cortical impact; LQC: Log quality control/check; MS: Mass spectrometry; RPLC: Reverse-phase liquid chromatography.
Figure 4
Figure 4. Systems biology-based selection of candidate traumatic brain-injury biomarkers, representing nonredundant and convergent pathways
BDP: Breakdown product; CRMP: Collapsin response mediator proteins; EMAP: Endothelial-monocyte activating polypeptide; GFAP: Glial fibrillary acidic protein; MBP: Myelin-basic protein; NSE: Neuron-specific enolase; SBDP: Spectrin breakdown product; TBI: Traumatic brain injury; UCH-L1: Ubiquitin C-terminal hydrolase-L1.
Figure 5
Figure 5. Basic sandwich antibody-based detection of traumatic brain-injury diagnostic biomarkers and the process of the development and validation of such assays and their clinical diagnostic utility testing
CV: Coefficients of variation; TBI: Traumatic brain injury.
Figure 6
Figure 6. Platform options for different applications
POC: Point of care; VA: Veterans affairs.

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