Presentation
Novel Blood Biomarkers of Diffuse Axonal Injury in Moderate-Severe Traumatic Brain Injury Patients
Description
Background and Purpose: Isolated diffuse axonal injury (DAI) is linked to unique biomarker signatures after moderate-severe traumatic brain injury (msTBI). Methods: As part of the NIH funded ProTECTIII/BioProTECT clinical trials, venipuncture serum samples were collected prospectively after acute TBI for analysis of blood biomarkers. Subjects (n=882) with GCS 4-12 were enrolled within 4h of msTBI at 45 US trauma centers. Sample collection occurred at baseline (<4h), 24h, and 48h post-injury. Neuroimaging was reviewed by a board-certified neuroradiologist. In subjects with complete biomarker sets, isolated DAI (DAI+) was identified on baseline CT (n=12) and follow-up CT/MRI (n=6). DAI- subjects (normal neuroimaging/discharge GCS=15, n=11) were age/sex matched from the study cohort. Blood biomarkers (n=187) were analyzed, from a diverse set of susceptible CNS cell types: neurons, microglia, and astrocytes. Multiplexed Olink® proximity extension assays were completed with inter-plate normalization. Temporal and relative changes in biomarker expression were compared across cohorts. Paired Welch’s T-Tests with Bonferroni-Holm post-hoc corrections were utilized to assess significance at p<0.05 (R4.3.3_RStudio2024.04.2+764). Results: Biomarkers that were elevated at baseline in DAI+ relative to DAI- cohorts included two cell-adhesion proteins: GB-2008 (p=0.043), GB-2009 (p<0.001), and one enzyme: GB-2040 (p=0.043). At 24h post-injury, eight biomarkers demonstrated significant elevations in DAI+ vs DAI- cohorts (p<0.019). At 48h post-injury, fifteen biomarkers were significantly elevated in DAI+ vs DAI- cohorts (p<0.042). Seven biomarkers were noted to be elevated across both timepoints for DAI+ patients only, including GB-0183, a novel mitochondrial biomarker. Uniquely, GB-2007, a signal transduction protein, was expressed equally across cohorts at baseline; however, levels increased in DAI+ patients at 24h (p=0.028) and remained low in DAI- patients throughout 48h. Conclusion: Blood biomarkers have unique signatures in msTBI patients with isolated DAI and can provide data-driven guidance for triage, diagnosis, and management after injury. Future research will correlate absolute and relative levels of DAI specific biomarkers with clinical outcomes.Event Type
Late-Breaking Abstract
TimeThursday, October 17th9:15am - 9:35am PDT
LocationHarbor Ballrooms B-C
Science of Neurocritical Care
Head and Spine Trauma
Seizures/EEG
Curing Coma
Intermediate