Biomarkers in traumatic brain injury (TBI): a review

Abstract

Biomarkers can be broadly defined as qualitative or quantitative measurements that convey information on the physiopathological state of a subject at a certain time point or disease state. Biomarkers can indicate health, pathology, or response to treatment, including unwanted side effects. When used as outcomes in clinical trials, biomarkers act as surrogates or substitutes for clinically meaningful endpoints. Biomarkers of disease can be diagnostic (the identification of the nature and cause of a condition) or prognostic (predicting the likelihood of a person’s survival or outcome of a disease). In addition, genetic biomarkers can be used to quantify the risk of developing a certain disease. In the specific case of traumatic brain injury, surrogate blood biomarkers of imaging can improve the standard of care and reduce the costs of diagnosis. In addition, a prognostic role for biomarkers has been suggested in the case of post-traumatic epilepsy. Given the extensive literature on clinical biomarkers, we will focus herein on biomarkers which are present in peripheral body fluids such as saliva and blood. In particular, blood biomarkers, such as glial fibrillary acidic protein and salivary/blood S100B, will be discussed together with the use of nucleic acids (eg, DNA) collected from peripheral cells.

Plasma Lipidomic Analyses in Cohorts With mTBI and/or PTSD Reveal Lipids Differentially Associated With Diagnosis and APOE ε4 Carrier Status

“…We also examined lipid species to determine whether specific lipid signatures could differentiate our three diagnostic groups. Functional magnetic resonance imaging and positron emission tomography have suggested metabolic changes in TBI (Dadas et al, 2018) and we have previously shown in these cohorts that several classes of plasma phospholipids including phosphatidylcholine (PC), lysoPC, phosphatidylethanolamine (PE), and lysoPE as well as sphingomyelin (SM) were all decreased in mTBI, PTSD, and mTBI + PTSD groups compared to controls (Emmerich et al, 2016). In the current study, we examined PS an additional PL as well as neutral lipids generally found in plasma lipid-rich lipoprotein particles responsible for transporting these lipids between various tissue including the brain and liver (Jonas and Phillips, 2008;Tracey et al, 2018).…”

“…Protein biomarkers currently used for TBI relate to either structural components of the brain (GFAP, neurofilaments, tau) or act as indicators of BBB injury (S100b, NSE) (Dadas et al, 2018). Therefore, these are likely to be more useful during the acute phases of the injury as a direct consequence of the physical damage but may not be as informative during sub-acute and chronic timepoints when biological changes likely reflect secondary consequences of injury, and the BBB is relatively intact, limiting their ability to enter the peripheral circulation.…”

“…Therefore, these are likely to be more useful during the acute phases of the injury as a direct consequence of the physical damage but may not be as informative during sub-acute and chronic timepoints when biological changes likely reflect secondary consequences of injury, and the BBB is relatively intact, limiting their ability to enter the peripheral circulation. This is especially problematic since the initial features of injury do not necessarily correlate with long-term outcomes for patients (Dadas et al, 2018), particularly in mild injuries where immediate biological effects are subtle, often undetectable, and may only manifest as secondary consequences of the initial insult (Prince and Bruhns, 2017). Therefore, biomarkers associated with mTBI or PTSD could improve diagnosis to ensure appropriate care and management of these conditions.…”

“…Therefore, biomarkers associated with mTBI or PTSD could improve diagnosis to ensure appropriate care and management of these conditions. Although neuroimaging has been an invaluable tool for improving our understanding of TBIand PTSD-related pathophysiology (Dadas et al, 2018;Dretsch et al, 2019) it is still limited in its utility over clinical measures (Dretsch et al, 2017a,b). Further, it is important to develop both cost effective and time efficient tools to track TBI-related changes while minimizing inconvenience to both patients and clinical staff.…”

Multimodal Neuromonitoring: Current Scenario in Neurocritical Care

“…Biomarkers, as NM tool, are used for diagnosis and prognosis of neurological diseases and can be qualitative and quantitative cerebral damage markers. 80 They may be present in blood, CSF, or saliva. They can predict pathophysiology, response to treatment, and side effects.…”