Abstract 2686: Plasma HMGB1 Concentration Correlates With The Inflammatory Response Following Stroke
Background: There is an inflammatory response following ischemic stroke that appears to contribute to brain injury and worsen outcome. High-mobility group box 1 (HMBG1) is a nuclear protein that is released from necrotic cells and serves as a “danger signal” which can initiate an inflammatory response in a non-infectious environment. We assessed whether early systemic HMGB1 could serve as a marker for infarct size and predict outcome and whether plasma HMGB1 would correlate with systemic markers of inflammation.
Methods: Plasma HMGB1 concentrations were analyzed in 114 patients with ischemic stroke at 1 (N=38), 3 (N=98), 7 (N=95), 30 (N=89), 90 (N=71), 180 (N=70) and 365 (N=24) days (blood samples were not available for all patients at all time points). A group of 40 “healthy” volunteers served as controls. Infarct volume was determined on diffusion weighted MRI and stroke severity by NIHSS score. The association between plasma HMGB1 and laboratory markers of inflammation was analyzed at each time point. Significance was set at P<0.05.
Results: There was only a modest correlation between the NIHSS score, infarct volume and early plasma HMGB1 (highest value by day 3) after stroke (r=0.248, P=0.009 and r=0.217, P=0.024, respectively). In comparison to controls, plasma HMGB1 was elevated to 30 days after stroke; patients with more severe strokes had higher plasma HMGB1 than patients with less severe stroke (Figure). There was a robust correlation between plasma HMGB1 and white blood cell (WBC) counts that was independent of stroke severity at 1 day after stroke (r=0.449, P=0.005). This relationship between plasma HMGB1 and WBC count persisted to 1 year after stroke (r=0.551, P=0.008) and was driven by polymorphonuclear cells (PMNs). Initial plasma HMGB1 was not predictive of long term outcome.
Conclusions: Plasma HMGB1 is elevated following ischemic stroke, and is higher in patients with more severe strokes. The robust and independent association of HMGB1 with WBC counts following stroke suggests that these cells may be the primary source of plasma HMGB1 following stroke.
- © 2012 by American Heart Association, Inc.