TIME COURSE OF BRAIN INJURY BIOMARKERS ACROSS TBI MODELS: FINDINGS FROM OPERATION BRAIN TRAUMA THERAPY.

This work, part of the Operation Brain Trauma Therapy (OBTT) a multi-center pre-clinical drug screening consortium, investigated the temporal course of circulating brain damage biomarkers and their associations with behavioral and histo-pathological outcomes across multiple traumatic brain injury (TBI) models. Levels of ubiquitin C-terminal hydrolase (UCH-L1) and glial fibrillary acid protein (GFAP) were serially measured 1 hr, 6 hr, and 24 hr following injury in rats subjected to controlled cortical impact (CCI), fluid percussion (FPI), or penetrating ballistic-like brain injury (PBBI). Sham rats underwent all manipulations except trauma. Both biomarkers were significantly increased as early as 1 hr after injury compared to shams with the exception of UCH-L1 in CCI. Higher UCH-L1 levels were consistently observed in sham and injured CCI groups when compared to the other models, albeit the levels remained unchanged over study duration across the groups. Conversely, GFAP concentration changed over time following injury, with magnitude and temporal profile differing significantly by group (interaction P < 0.001). Specifically, contrasting the acute elevation following FPI and PBBI, a delayed peak in GFAP at 6 hr was observed after CCI. UCH-L1 and GFAP at 1 hr correlated with latency to find the platform across models, and with the performance in the probe trial in FPI and PBBI. UCH-L1 at 1 hr also correlated with lesion volume and tissue loss in CCI. This study provides direct evidence of differential release kinetics of GFAP across distinct injury models supporting the adoption of an adjusted diagnostic time window for detection of TBI based on the injury type. Furthermore, these data support the acute measurement of UCH-L1 and GFAP as potential surrogates for behavioral outcomes. [ABSTRACT FROM AUTHOR]