531 Novel inflammatory gene expression changes occur within the occluded vasculature of large vessel ischemic stroke

Objectives/Goals: We hypothesized that the bulk transcriptomic profiling of blood collected from within the ischemic vasculature during an acute ischemic stroke with large vessel occlusion (LVO) will contain unique biomarkers that are different from the peripheral circulation and may provide much-needed insight into the underlying pathogenesis of LVO in humans. Methods/Study Population: The transcriptomic biomarkers of Inflammation in Large Vessel Ischemic Stroke pilot study prospectively enrolled patients ≥ 18 years of age with an anterior circulation LVO, treated with endovascular thrombectomy (EVT). Two periprocedural arterial blood samples were obtained (DNA/RNA Shield™ tubes, Zymo Research); 1) proximal to the thrombus, from the internal carotid artery and 2) immediately downstream from the thrombus, by puncturing through the thrombus with the microcatheter. Bulk RNA sequencing was performed and differential gene expression was identified using the Wilcoxon signed rank test for paired data, adjusting for age, sex, use of thrombolytics, last known well to EVT, and thrombolysis in cerebral infarction score. Bioinformatic pathway analyses were computed using MCODE and reactome. Results/Anticipated Results: From May to October 2022, 20 patients were screened and 13 were enrolled (median age 68 [SD 10.1], 47% male, 100% white). A total of 608 differentially expressed genes were found to be significant (p-value) Discussion/Significance of Impact: These results provide evidence of significant gene expression changes occurring within the ischemic vasculature of the brain during LVO, which may correlate with larger ischemic infarct volumes and worse functional outcomes at 90 days. Future studies with larger sample sizes are supported by this work.