Plasma ceramides are associated with outcomes in acute ischemic stroke patients

Abstract

Sphingolipids are major constituents of eukaryotic cell membranes and play key roles in cellular regulatory processes. Our recent results in an experimental stroke animal model demonstrated changes in sphingolipids in response to acute ischemic brain injury. This study aimed to investigate the plasma levels of sphingosine-1-phosphate (S1P) and ceramides in acute ischemic stroke (AIS) patients and their associations with functional outcomes. Plasma samples were collected from patients with AIS at <48 and 48-72h post stroke and from nonstroke controls. The levels of S1P and ceramides with different fatty acyl chain lengths were measured by the ultra-high-pressure liquid chromatography-electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS). A poor functional outcome was defined as a modified Rankin Scale (mRS) score ≥2 at 3 months after AIS. The results showed that S1P and very-long-chain ceramides were significantly decreased in AIS patients (n=87; poor outcome, 56.3%) compared to nonstroke controls (n=30). In contrast, long-chain ceramides were significantly increased in AIS patients. More importantly, higher levels of Cer(d18:1/18:0), Cer(d18:1/20:0), and Cer(d18:1/22:0) at 48-72h were significantly associated with poor functional outcomes after adjusting for potential clinical confounders, including age, sex, hypertension, and National Institutes of Health Stroke Scale score at admission. Our study supported the dynamic metabolism of sphingolipids after the occurrence of AIS. Ceramides could be potential prognostic markers for patients with AIS.