167 High Throughput Metabolite Profiling Identifies Plasma Anandamide as a Biomarker of Functional Outcome After Aneurysmal Subarachnoid Hemorrhage
Abstract INTRODUCTION The quantification of metabolites in plasma samples in patients with aneurysmal subarachnoid hemorrhage (aSAH) can highlight important alterations in critical metabolic pathways. As metabolites reflect changes associated with disease conditions, metabolite profiling (metabolomics) can identify candidate biomarkers for disease and potentially uncover pathways for intervention. METHODS We performed high throughput metabolite profiling across a broad spectrum of chemical classes (173 metabolites) on plasma samples taken from 119 patients with aSAH. Samples were drawn at 3 time points following ictus: 2–4, 7–10, and 12–14 days. Univariate and logistic regression analyses were performed to examine the relation of each metabolite with multiple outcome variables, including short- and long-term functional outcome (modified Rankin Scale, mRS). RESULTS >A good functional outcome (mRS 0–2) was found in 63.1% and 66.7% of patients at 30 and 90 days, respectively, following aSAH. Plasma concentrations of the endogenous cannabinoid anandamide during days 2–4 after aneurysmal SAH were decreased by 48.1% (P < 0.0001) and 57.6% (P <0.0001) in patients with mRS 0–2 at 30 and 90 days, respectively. A similar statistical result was noted with plasma anandamide concentrations averaged across all time periods. Logistic regression further demonstrated that anandamide remained an independent predictor of functional outcome (30 days: P = 0.04; 90 days: P = 0.03), even after adjusting for other factors that influence outcome, including age, World Federation of Neurological Surgeons grade (WFNS), Fisher grade, and symptomatic vasospasm. CONCLUSION Decreased plasma anandamide following aSAH predicts a good functional outcome at 30 and 90 days. While a role for anandamide in aneurysmal SAH has not been previously reported, elevated anandamide levels have been implicated in neuronal apoptosis and cerebral edema in the acutely injured brain. These data highlight the increasing capability of metabolomics techniques in profiling large-sized cohorts to illuminate novel markers of disease and potential metabolic regulators.