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.

Neurospecific Molecules Measured in Periphery in Humans: How Do They Correlate with the Brain Levels? A Systematic Review

“…Exosomes are considered to mirror heterogeneous biological changes that occur during the progression of neuropsychiatric diseases [ 67 ]. Animal and human studies demonstrated an accuracy of several types of exosomes and miRNAs in detecting mild, moderate, and severe traumatic brain injury [ 68 ]. Moreover, as a novel class of circulating biomarkers, exosomes can provide new insights on the biophysical and/or biochemical properties of biomolecules of brain origin.…”

Experimental and Clinical Biomarkers for Progressive Evaluation of Neuropathology and Therapeutic Interventions for Acute and Chronic Neurological Disorders

“…miRNAs are a class of small, endogenous, and highly conserved non-coding RNAs that are an average of 17–25 nucleotides in length [ 10 , 256 ]. miRNAs play vital roles in protein synthesis and regulating gene expression in the post-transcriptional phase [ 257 ].…”

“…There are a few miRNAs that are only expressed in a brain-specific or brain-enriched manner [ 258 ]. These endogenous molecular regulators appeared to be distorted in different pathologies, including TBI [ 10 ]. Thus, they have been widely reported as new potential biomarkers for the diagnosis and prognosis of a range of diseases.…”

The evolving role of extracellular vesicles (exosomes) as biomarkers in traumatic brain injury: Clinical perspectives and therapeutic implications

“…However, because of the restrictions in their diffusion over the BBB, blood levels of free circulating proteins and mRNA are readily degraded and can fall below detection levels for identification. Furthermore, the provenance of the tissue is unclear, limiting the interpretation of potential mechanistic contributions (Ghaith et al, 2022 ). As a result, there is an unmet clinical need for accurate biomarkers that can identify all TBIs, including mTBI, and predict the likelihood of developing long-term sequelae, including post-concussive syndrome chronic traumatic encephalopathy (Ghaith et al, 2022 ; Mavroudis et al, 2022 ).…”

“…Furthermore, the provenance of the tissue is unclear, limiting the interpretation of potential mechanistic contributions (Ghaith et al, 2022 ). As a result, there is an unmet clinical need for accurate biomarkers that can identify all TBIs, including mTBI, and predict the likelihood of developing long-term sequelae, including post-concussive syndrome chronic traumatic encephalopathy (Ghaith et al, 2022 ; Mavroudis et al, 2022 ). Recent research has revealed that circulating exosomes enriched for CNS-specific tissue sources may be a method to develop practical biomarkers for TBI, particularly mild TBI, to circumvent these difficulties (Goetzl et al, 2019 , 2020 ; Winston et al, 2019 ; Vaughn et al, 2021 ).…”