Potential Blood-based Biomarkers for Concussion

Abstract

Mounting research in the field of sports concussion biomarkers has led to a greater understanding of the effects of brain injury from sports. A recent systematic review of clinical studies examining biomarkers of brain injury following sports-related concussion established that almost all studies have been published either in or after the year 2000. In an effort to prevent chronic traumatic encephalopathy and long-term consequences of concussion, early diagnostic and prognostic tools are becoming increasingly important; particularly in sports and in military personnel, where concussions are common occurrences. Early and tailored management of athletes following a concussion with biomarkers could provide them with the best opportunity to avoid further injury. Should blood-based biomarkers for concussion be validated and become widely available, they could have many roles. For instance, a point-of-care test could be used on the field by trained sport medicine professionals to help detect a concussion. In the clinic or hospital setting, it could be used by clinicians to determine the severity of concussion and be used to screen players for neuroimaging (computed tomography and/or magnetic resonance imaging) and further neuropsychological testing. Furthermore, biomarkers could have a role in monitoring progression of injury and recovery and in managing patients at high risk of repeated injury by being incorporated into guidelines for return to duty, work, or sports activities. There may even be a role for biomarkers as surrogate measures of efficacy in the assessment of new treatments and therapies for concussion.

Figure 1

Picture of the neuron and the neuroanatomic locations of potential TBI biomarkers. S100β is the major low affinity calcium binding protein in astrocytes that helps to regulate intracellular levels of calcium. Glial Fibrillary Acidic Protein (GFAP) is a monomeric intermediate protein found in astroglial skeleton that is found in white and gray brain matter and is strongly upregulated during astrogliosis. Neuron specific enolase (NSE) is one of the five isozymes of the gycolytic enzyme enolase found in central and peripheral neuronal cell bodies. UCH-L1 is highly abundant in neurons and was previously used as a histological marker for neurons. Alpha-II-spectrin is the major structural component of the cortical membrane cytoskeleton and is particularly abundant in axons and presynaptic terminals. Tau is an intracellular, microtubule-associated protein that is highly enriched in axons. Neurofilaments are heteropolymeric components of the neuron cytoskeleton. (Taken from Papa, L.: Exploring Serum Biomarkers for Mild Traumatic Brain Injury. In: Brain Injury Principles: Molecular, Neuropsychological, and Rehabilitation Aspects in Brain Injury Models. Kobeissy F. [ed]: CRC Press/Taylor & Francis, 2015, Figure 22.1, p 303)