A Literature Review of Traumatic Brain Injury Biomarkers

Abstract

Research into TBI biomarkers has accelerated rapidly in the past decade owing to the heterogeneous nature of TBI pathologies and management, which pose challenges to TBI evaluation, management, and prognosis. TBI biomarker proteins resulting from axonal, neuronal, or glial cell injuries are widely used and have been extensively studied. However, they might not pass the blood-brain barrier with sufficient amounts to be detected in peripheral blood specimens, and further might not be detectable in the cerebrospinal fluid owing to flow limitations triggered by the injury itself. Despite the advances in TBI research, there is an unmet clinical need to develop and identify novel TBI biomarkers that entirely correlate with TBI pathologies on the molecular level, including mild TBI, and further enable physicians to predict patient outcomes and allow researchers to test neuroprotective agents to limit the extents of injury. Although the extracellular vesicles have been identified and studied long ago, they have recently been revisited and repurposed as potential TBI biomarkers that overcome the many limitations of the traditional blood and CSF assays. Animal and human experiments demonstrated the accuracy of several types of exosomes and miRNAs in detecting mild, moderate, and severe TBI. In this paper, we provide a comprehensive review of the traditional TBI biomarkers that are helpful in clinical practice. Also, we highlight the emerging roles of exosomes and miRNA being the promising candidates under investigation of current research.

Keywords: Biomarkers; Exosomes; Head injury; Traumatic brain injury; miRNA.

Fig. 1

Flow diagram of the different types of TBI biomarkers that denote many processes such as neuronal injury, glial injury, axonal injury, and inflammation. NSE: neuron-specific enolase; UCH-L1: ubiquitin C-terminal hydrolase-L1; GFAP: glial fibrillary acidic protein; and MBP: myelin basic protein

Fig. 2

Bar chart showing area under the curve of diagnostic accuracy of miRNAs in TBI diagnosis. *Combined miRNAs = miR-29c-3p + miR-26b-5p + miR-30e-5p + miR-182-5P + miR-320c + miR-221-3p. Data are generated from the studies listed in Table 2