Abstract WP209: Changes In Serum Superoxide Dismutase 3 (sod3) Following Acute Ischemic Stroke: A Pilot Study

Abstract

Introduction: Acute ischemic stroke (AIS) elicits peripheral immune activation and reactive inflammatory changes within the lung that contribute to cerebral reperfusion injury. Expression of the antioxidant SOD3 within the lung exerts an intrinsic anti-inflammatory bias on the systemic vasculature. In preclinical models, lung and serum SOD3 levels decline acutely following AIS, while enforced lung SOD3 expression blunts post-stroke inflammation and reperfusion injury. Linking changes in serum SOD3 with stroke severity in a clinical context could have important diagnostic and therapeutic implications. Objectives: 1) Compare serum SOD3 levels among AIS patients vs. controls at initial hospital presentation; 2) Evaluate changes in serum SOD3 in AIS patients during hospitalization; 3) Establish whether serum SOD3 levels correlate with stroke severity. Methods: Inclusion criteria : patients (≥18 years) presenting with AIS (n=7) not treated with either tPA or thrombectomy. Patients with MRI-negative TIA or stroke mimics served as controls (n=8). Exclusion criteria : history of stroke or ICH, seizure at presentation, infection or trauma in the past 30 days, malignancy, autoimmune disease, or major surgery within 90 days. Analyses: Baseline (12-24 hours from LKN) and serial serum samples (1-7 days) were analyzed by automated capillary Western for total SOD3 and compared against the presenting NIH stroke scale score. Results: Analyses revealed 35% (range +9% to -53%) lower initial SOD3 levels in patients with acute ischemic stroke vs. controls, with NIHSS scores ranging from 0 to 10 (median 0.5). Median SOD3 levels in AIS patients were 45,204, 31214, and 41,133 AUC (area under curve) at 12, 24, and 72 hours, respectively. While differences between median peak to nadir SOD3 levels were significant (52117 ± 16052 vs. 27798 ± 7529, p=0.015, two-tailed t-test) in AIS patients, serum SOD3 levels did not correlate with stroke severity. Conclusion: These results suggest minor ischemic stroke is associated with acute reductions in serum SOD3. While further study is required, this finding has potential clinical implications when considering the potential utility of SOD3 as a disease marker and potential therapeutic in the setting of AIS.