Abstract P430: Inflammatory Survival Gene Expression Patterns Differentiate Favorable and Unfavorable Outcomes Following Surgical Intervention in Intracerebral Hemorrhage

Abstract

Background and Aims: Surgical management of intracerebral (ICH) remains controversial due to unclear benefit. In this study, we analyzed temporal changes in expression of proinflammatory and anti-inflammatory survival genes to discern the molecular differences between favorable and unfavorable outcomes after surgery. Methods: Venous blood collected in Paxgene Blood RNA from ICH patients before surgery at ‘early’ (Day 0-2) and at ‘delayed’ (Day 3-5) timepoints. Extracted total RNA was used for real-time Taqman PCR analysis for anti-inflammatory, survival genes superoxide dismutase 1(SOD1), COX-2, IL-10, peroxisome proliferator activated receptor gamma (PPARG), TGF-B1, and IL-10. The pro-inflammatory genes included arginase-1 (ARG1), TNF, IL-1B, monocyte/macrophage activity markers (CD36, CD163) and NF-kB members (NFKB1, NFKB2, RELA, RELB, REL, NFKBIA). Relative fold changes were determined after normalizing to GAPDH. 90-day Modified Rankin Score (mRS) were collected and classified as favorable, mRS 0-3 (n=4) and unfavorable, mRS 4-6 (n=8). Statistical analysis was carried out by Welch’s ANOVA test (p<0.05). Results: Mean age was 56.25yrs (SD 19.7). ICH location was 10 deep nuclei (thalamus or basal ganglia), 1 cerebellum, and 1 lobar. ICH volume was lower in the mRS 0-3 group (24.15ml SD21.2 vs 35.8ml SD 31.7 p=0.68). All patients had a decompressive hemicraniectomy and 7 included hematoma evacuation. Overall, the NFkB family gene expression was increased at ‘delayed’ relative to the early time points in both groups. However, RELB expression was significantly higher at the early time point of mRS 0-3 compared to mRS 4-6 group. Expression of ARG1, SOD1, COX2, IL-1B, IL-10, TGF-B1, PPARG and CD36 increased significantly at the delayed compared to the early time point. In the unfavorable outcome group (mRS 4-6), TNF expression increased significantly at the delayed timepoints compared to mRS 0-3 which was unchanged. Conclusions: The studied genes were highly expressed and differed significantly between time points. TNF was significantly expressed at the delayed time point in the mRS 4-6 group but unchanged in the mRS 0-3 group. Further studies will explore the role of TNF and related genes in patient selection and outcomes for surgical management of ICH.