Biomarkers of mild traumatic brain injury in cerebrospinal fluid and blood

Abstract

Mild traumatic brain injury (TBI), which is defined as a head trauma resulting in a brief loss of consciousness and/or alteration of mental state, is usually benign, but occasionally causes persistent and sometimes progressive symptoms. Whether a threshold for the amount of brain injury and/or individual vulnerability might contribute to the development of these long-term consequences is unknown. Furthermore, reliable diagnostic methods that can establish whether a blow to the head has affected the brain (and in what way) are lacking. In this Review, we discuss potential biomarkers of injury to different structures and cell types in the CNS that can be detected in body fluids. We present arguments in support of the need for further development and validation of such biomarkers, and for their use in assessing patients with head trauma in whom the brain might have been affected. Specifically, we focus on the need for such biomarkers in the management of sports-related concussion, the most common cause of mild TBI in young individuals, to prevent long-term neurological sequelae due to concussive or subconcussive blows to the head.

Figure 1

Possible biomarkers of traumatic brain injury. These molecules include NSE, SBPs and UCH-L1, which are all enriched in the neuronal cytoplasm. NFL is a biomarker of injury to large-calibre myelinated axons. Total tau is a biomarker of injury to thin nonmyelinated axons. APP and amyloid-β are produced in axon terminals and might be involved in synaptic activity and plasticity. Overproduction of amyloid-β in response to trauma could result in formation of diffuse amyloid plaques. Injury to astroglial cells may lead to release of S100-B and GFAP into the extracellular matrix, which might increase S100-B levels in both cerebrospinal fluid and blood. Astrogliosis and post-injury neuroinflammation can result in increased production of interleukins and cytokines. Integrity of the blood–brain barrier is indicated by the cerebrospinal fluid:serum albumin ratio. Abbreviations: APP, amyloid precursor protein; GFAP, glial fibrillary acidic protein; MBP, myelin basic protein; NFL, neurofilament light polypeptide; NSE, γ-enolase; SBPs, spectrin breakdown products; UCH-L1, ubiquitin carboxyl-terminal hydrolase isoenzyme L1.