Abstract
Background: The pathogenesis of brain injury after subarachnoid hemorrhage (SAH) is multifactorial and not completely understood. We recently described that profound changes in the ceramide (Cer) profile occur after SAH. Cer is an endogenous sphingolipid associated with brain-cell death. Dihydroceramide (DH-Cer) is an inactive sphingolipid that is metabolized into Cer by desaturases. In this study we sought to investigate if a differential metabolism of Cer into DH-Cer occurs in SAH and if this is related to vasospasm (VS) and outcome. Methods: Cerebrospinal fluid (CSF) Cer and DH-Cer levels were determined by mass spectrometry in control subjects and patients with Fisher 3 grade SAH within 48 hours of the bleed. Patients were prospectively followed and subcategorized based on the presence or absence of symptomatic VS (sVS versus no-sVS) and modified Rankin Scale (mRS) at discharge. Results: A total of 8 controls and 23 SAH patients were enrolled in the study. Compared to controls, patients with SAH had higher CSF levels of total Cer (12.41±8.84 versus 54.65±49.30 pmol/mL, p=0.001) and DH-Cer (1.44±1.05 versus 4.73±3.43 pmol/mL, p<0.0001). Cer/DH-Cer ratios in both groups were comparable (p>0.05). Within the SAH group, sVS had higher Cer and DH-Cer levels than no-sVS (104.23±56.97 versus 28.60±16.91 pmol/mL, p=0.001 for Cer; 7.87±4.03 versus 3.12±1.88 pmol/mL, p=0.005 for DH-Cer). In addition, the sVS group had lower Cer/DH-Cer ratios than no-sVS (0.11±0.03 versus 0.08±0.02; p=0.009). Compared to individuals with good outcome (mRS≤3), SAH patients with poor outcome (mRS≥4) had lower Cer/DH-Cer ratios (0.12±0.04 versus 0.09±0.02; p=0.04) Conclusions: CSF levels of Cer and DH-Cer increase after SAH, particularly in individuals with sVS and poor neurological outcome at discharge. The distinctive Cer/DH-Cer ratios observed in sVS and no-sVS groups suggest that differences in sphingolipid metabolism exist in these subgroups.
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