Ceramide Dynamics and Prognostic Value in Acute and Subacute Ischemic Stroke: Preliminary Findings in a Clinical Cohort

Abstract

Background: Ceramides are implicated in sphingolipid signaling. Elevated ceramide levels have been associated with increased cardiovascular risk, but information on their role in acute ischemic stroke (AIS) is limited. The purpose of this study is to investigate the temporal dynamics of ceramide levels in AIS and assess their prognostic utility for long-term outcomes. Methods: This is a prospective pilot study of patients with AIS admitted to Mayo Clinic within 12 h of last known well (LKW). Ceramides were assessed by liquid chromatography mass spectrometry at two time points: T1 (within 12 h of LKW) and T2 (1 - 7 days from LKW). Wilcoxon signed rank test was used to compare paired ceramide levels and ratios. Ordinal logistic regression was used for assessment of associations with long-term outcomes. Results: Twenty-three patients met inclusion criteria (median (range)): age (76 years (45 - 95)); body mass index (25.6 (20.5 - 46.6)); National Institutes of Health Stroke Scale (NIHSS) score (5 (0 - 27)); infarct volume (1.4 cm 3 (0.0 - 36.5)). Long-chain ceramides increased between T1 and T2 whereas very-long chain ceramides decreased, P < 0.05. Upon stratification of patients by prior statin exposure, increase in long-chain ceramide level was present only in statin-naive patients. Greater neurological disability at follow-up was associated with higher ceramide score, C(18:0)/C(24:0) ratio and higher levels of glycated hemoglobin. Conclusions: Long-chain and very-long-chain ceramide are actively implicated in pathologic processes in acute and subacute phases of stroke, with their dynamics being inversely related and potentially modulated by statin therapy. Ceramide levels and ratios might be useful for prognosis of long-term neurological outcomes. J Neurol Res. 2020;10(6):209-219 doi: https://doi.org/10.14740/jnr633