Angiopoietin2 (Ang2) Levels are Associated with Increased Severity and Unfavorable Outcomes in Traumatic Brain Injury (TBI): A TRACK-TBI Study
Andres Nunez1, Rachel Thomas1, Katie Brecker2, Catherine Demos3, Sonia Jain4, Xiaoying Sun4, Joseph Giacino5, Michael McCrea6, David Okonkwo7, Claudia Robertson8, Pratik Mukherjee9, Kevin Wang10, Ava Puccio7, Andrea Schneider2, Danielle Sandsmark2, Geoffrey Manley11, Alexa Walter2, Ramon Diaz-Arrastia2
1Neurology, University of Pennsylvania, 2University of Pennsylvania, 3MesoScale Discoveries, 4University of California, San Diego, 5Massachusetts General Hospital, 6Medical College of Wisconsin, 7University of Pittsburgh, 8Baylor College of Medicine, 9University of California, San Francisco, 10Morehouse University, 11UCSF Med Ctr/Dept of Neurosurgery
Objective:
Describe the relationship of Ang2 levels in plasma with TBI severity, CT findings, and how it evolves in the first two weeks after injury.
Background:
Ang2 is a naturally occurring antagonist of Tie2 which plays a role in pathophysiological processes related to vascular injury and repair. TBI is often associated with microvascular disruption, and we hypothesize that Ang2 levels measured in plasma are a sensitive biomarker of microvascular injury.
Design/Methods:
A subset of the TRACK-TBI cohort consisting of adults with TBI (n=362), orthopedic injury controls (OI, n=89), and healthy controls (HC, n=64) was analyzed. Plasma was collected at 1 day (D1), 2 weeks (W2), and 6 months (M6) after injury, and Ang2 levels were measured using Meso Scale Discovery (MSD) R-PLEX assay. Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) were measured on MSD Neurology Panel S-Plex.
Results:
The mean age of the TBI participants was 39.8 years. 174 (48%) were GCS 13-15, and 188 (52%) were GCS 3-12. D1 Ang2 levels (median [IQR]) in TBI cases were 2.4 [1.8–3.9] ng/mL, compared to 1.7 [1.3–2.1] ng/mL in HC (p<0.001) and 2.2 [1.6–2.7] ng/mL in OI (p=0.008). Ang2 remained elevated at W2 in GCS 3-12 cases (3.3 [2.3–5.1] ng/mL), but returned to normal by M6. In the GCS 13-15 cases, Ang2 levels had returned to normal by W2. Higher levels on D1 and W2 are associated with TBI severity. D1 Ang2 levels in cases with abnormal CT was 2.9 [2.0–4.5] ng/mL, while in CT negative cases it was 2.0 [1.5–2.5] ng/mL (p<0.0001).
Conclusions:
Ang2 is increased after TBI, and in severely injured cases higher levels persist for 2 weeks. Ang2 is a biomarker of traumatic microvascular injury and deserves further investigation.
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