Plasma biomarkers in chronic mild traumatic brain injury: A review

Background/Objective: Understanding the biological cascade which results from a mild traumatic brain injury (mTBI) is essential to determine outcomes over time. Acute plasma levels of brain-related injury markers (BRIMS; ubiquitin carboxy-terminal hydrolase L1 [UCH-L1], total tau[t-tau], neurofilament light chain [NfL], S100 calcium-binding protein β [S100β], glial fibrillary acidic protein [GFAP]) are typically elevated in patients post-mTBI, and relate to injury severity, distinguish neuroimaging findings, and to some degree, relate to functional outcomes. However, acute assessment of biomarkers post-injury is not always feasible, and studies assessing biomarkers in the chronic phase of mTBI have yielded less consistent findings. Method: This review aims to (1) summarize the current literature on the most frequently examined BRIMS in mTBI, (2) review prior research in chronic assessment of BRIMS post-mTBI, (3) discuss the relationship between chronically assessed BRIMS and outcomes post-injury, (4) discuss the relationship between chronically assessed BRIMS and cognition including use by neuropsychologists, (5) discuss limitations to chronic assessment, and (6) discuss recent advances in measurement. Results: There is some evidence that NfL and various inflammatory markers may continue to be elevated and differentiate mTBI from controls during the chronic phase of mTBI; however, findings are inconsistent. During the chronic phase, biomarkers such as UCH-L1, S100β, GFAP, and t-tau appear to be mostly comparable between mTBI and controls. Conclusion: Given the limitations in the chronic assessment of plasma biomarkers after mTBI, researchers should continue efforts in discovery-based methods to identify biomarkers which are more reflective of the pathological processes occurring within the chronic phase of mTBI.