Abstract WP256: Favorable Outcome In Intracerebral Hemorrhage Is Associated With With Higher 15-lox-1 Expression

Abstract

Background: In previous studies, we identified a higher abundance of the docosanoid, Neuroprotectin D1 (NPD1), a lipid anti-inflammatory mediator, in intracerebral hemorrhage (ICH) patients with favorable outcome. In this study, we hypothesized that favorable outcome is due to increased expression of 15-LOX-1, a critical enzyme in the endogenous synthesis of NPD1 compared with patients with unfavorable outcome. Methods: After informed consent, whole blood were collected in PaxGene blood RNA tubes from consecutive patients with acute spontaneous ICH within 48 hours of admission. Total RNA was used for real-time PCR using Taqman probe for 15-LOX-1. The PCR cycle threshold (Ct) of 15-LOX-1 was normalized to the endogenous control GAPDH and fold change determined. Demographic and clinical data were collected. Outcome measures included 90-day modified Rankin score. In this study favorable outcome is defined as MRS 0-3 (n=11) and unfavorable outcome as MRS 4-6 (n=25). Results: Thirty-six patients were included in the study with a mean age of 61.9 years (SD 13.1). In patients with favorable outcome, the mean normalized Ct for 15-LOX-1 was 3.5 (SD 1.8) while in unfavorable was 8.9 (SD 3.8), and for normal healthy was 1.4 (SD 0.4). Expression of 15-LOX-1 was 43-fold higher in patients with favorable outcome. Conclusion: The increased expression of 15-LOX-1 suggests a significant synthesis and abundance of NPD1 in patients with MRS 0-3 compared with patients with MRS 4-6 and suggests that early synthesis and abundance of NPD1 is likely an important protective mediator in ICH pathophysiology