Abstract Body (Do not enter title and authors here): Background: Acute ischemic stroke (AIS) is a leading cause of mortality and disability globally, disproportionately affecting Black and Latinx populations who experience increased morbidity and mortality compared to their white counterparts. At one month, roughly 50% of AIS survivors experience mood disturbances (e.g., anger, irritability, and aggression) and exhibit a lower health-related quality of life (HRQOL) compared to pre-AIS levels. Downstream biomarkers of mitochondrial dysfunction such as oxidative stress may be important pathophysiological mechanisms underlying mood disturbance symptoms, stroke severity, and long-term functional recovery.

Purpose: To examine associations among early and late peripheral plasma lipid levels, mood disturbance symptoms (e.g., anger, irritability), and HRQOL outcome over 3 months (baseline/study day 5, and months 1, 3) in persons following AIS.

Methods: The pilot study is a non-probability, convenience sample of adult subjects (> 18 years of age) with a diagnosis of AIS. Lipidomics analysis was performed using liquid chromatography-mass spectrometry (LC-MS) of untargeted lipids. The Agilent 6545 LC/Q-TOF platform was used to determine the absolute concentration of lipid species from peripheral plasma samples collected days 1, 3, 5 and months 1 and 3 post-AIS. General linear mixed models were used to test the predictive association of lipidomic biomarker mean value of peripheral plasma lipid levels and symptoms and outcomes over time (baseline and months 1 and 3).

Results: We analyzed 82 subjects (age = 64 ± 12.1, 52% male, 78% Black, and 94% with hypertension). Elevated oxidative stress biomarkers (e.g., lipoxygenases, arachidonic acid, glycosylphosphatidylinositol) were associated with higher severity of anger and irritability symptoms, and a poorer HRQOL from baseline to 1- and 3-months post-AIS (p=0.04).

Conclusion: An untargeted LC-MS lipidomics approach was used to identify lipids following AIS. Because oxidative stress plays a key regulatory role in complex downstream cellular function, these findings may be of great significance in understanding AIS pathophysiology that has the potential to inform personalized preventive strategies.