Objective:

Investigate levels of PlGF in plasma after TBI, and assess relationships to injury severity and evolution. 

Background:

PlGF is an angiogenic factor that plays a key role in vasculogenesis, wound healing, and other physiological processes. It is elevated in cases of vascular cognitive impairment/dementia in elderly patients with white matter hyperintensities (WMHs) on MRI. Microvascular disease, WMHs, and cognitive impairment are often present in victims of TBI at younger ages than in the general population. We hypothesize that PlGF is elevated in plasma after TBI. 

Design/Methods:

A subset of the TRACK-TBI cohort consisting of adults with TBI (n=367), orthopedic injury controls (OC, n=86) and healthy controls (HC, n=69) was analyzed. Plasma was collected 1 day (D1), 2 weeks (W2), and 6 months (M6) post-injury. PlGF was measured using a MesoScale Discovery (MSD) V-Plex assay. 

Results:

TBI participants had a mean (SD) age of 39.6 (16.1) years. Those with GCS 3-12 at presentation (n=179) had significantly elevated PlGF levels on D1 (median [IQR] 12.1 [8.8-16.1] pg/mL), compared to HC (9.1 [7.6-10.7] pg/mL) or OC participants (8.3 [6.3-11.0] pg/mL), p<.0001 for all comparisons. TBI subjects with GCS 13-15 (n=188) did not have elevated PlGF levels (8 [6.6-10.4] pg/mL) on D1. CT positive TBI participants (n=227) had elevated PlGF on D1 (11.4 [8.2-15.4] pg/mL) compared to CT negative participants (7.8 [6.4-10.0] pg/mL) p<.0001. PlGF remained elevated in TBI participants with GCS 3-12 (10.6 [8.6-13.6] pg/mL) compared to GCS 13-15 (7.4 [6.3-9.2] pg/mL) or OC (7.8 [6.6-9.6] pg/mL) at W2 but normalized by M6 (8.3 [6.6-9.7] pg/mL). 

Conclusions:

PlGF is significantly elevated post-TBI in cases with GCS 3-12 on D1 and remains elevated at W2 compared to GC2 13-15 TBI or OC subjects. PlGF shows promise as a biomarker of traumatic microvascular injury, particularly in more severely injured individuals.