Advances in Traumatic Brain Injury Biomarkers

Abstract

Traumatic brain injury (TBI) is increasingly a major cause of disability across the globe. The current methods of diagnosis are inadequate at classifying patients and prognosis. TBI is a diagnostic and therapeutic challenge. There is no Food and Drug Administration (FDA)-approved treatment for TBI yet. It took about 16 years of preclinical research to develop accurate and objective diagnostic measures for TBI. Two brain-specific protein biomarkers, namely, ubiquitin C-terminal hydrolase-L1 and glial fibrillary acidic protein, have been extensively characterized. Recently, the two biomarkers were approved by the FDA as the first blood-based biomarker, Brain Trauma Indicator™ (BTI™), via the Breakthrough Devices Program. This scoping review presents (i) TBI diagnosis challenges, (ii) the process behind the FDA approval of biomarkers, and (iii) known unknowns in TBI biomarker biology. The current lag in TBI incidence and hospitalization can be reduced if digital biomarkers such as hard fall detection are standardized and used as a mechanism to alert paramedics to an unresponsive trauma patient.

Inflammation biomarkers IL‑6 and IL‑10 may improve the diagnostic and prognostic accuracy of currently authorized traumatic brain injury tools

“…UCH-L1 has been previously proposed to be an important index of TBI classification and prognostication ( 23 , 53 ), whilst other studies also support their significant associations with outcome ( 54 ). However, they did not highlight their potential predictive power in TBI prognostic models ( 54 ).…”

“…In terms of molecular biomarkers, ubiquitin C-terminal hydrolase L1 (UCH-L1) is considered to be a protein biomarker for neuronal cell body injury, whereas glial fibrillary acidic protein (GFAP) is generally considered as a biomarker for astro-glial injury (10,22). UCH-L1 is a deubiquitinating neuronal enzyme, whilst GFAP is a monomer of intermediate filaments forming the astrocytic cytoskeleton (23)(24)(25). The i-STAT TBI Plasma test, which measures both UCH-L1 and GFAP, has been approved by the U.S. Food and Drug Administration for the detection of possible candidates for CT scan, between patients with mild TBI discrimination in adults (26).…”

Delayed progressive intracranial bleeding in pediatric acute epidural hemorrhage treated expectantly

“…Current update of diagnostic biomarker is Brain Trauma Indicator™ (BTI™), which is the first blood-based biomarker for TBI, which has been approved by the Food and Drug Administration of the United States (FDA). BTI™ measures assesses two brain-specific protein biomarkers: ubiquitin C-terminal hydrolase-L1 and glial fibrillary acidic protein (GFAP) [9] .…”

Innovative Insights into Traumatic Brain Injuries: Biomarkers and New Pharmacological Targets

“…Emerging evidence underscores the significance of specific blood biomarkers such as neurofilament light chain (NF-L), ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1), Tau, S100B, and glial fibrillary acidic protein (GFAP) [22]. Recently, using the Breakthrough Devices Program, UCH-L1 and GFAP were approved by the Food and Drug Administration (FDA) as the first blood-based biomarker called the Brain Trauma Indicator™ (BTI™) [23].…”