Correlation of F4-neuroprostanes levels in cerebrospinal fluid with outcome of aneurysmal subarachnoid hemorrhage in humans

Aneurysmal subarachnoid hemorrhage (aSAH) is one type of hemorrhagic stroke in humans. F2-isoprostanes (F2-IsoPs) and F4-neuroprostanes (F4-NPs), derived from arachidonic acid and docosahexaenoic acid (DHA), respectively, are specific markers of lipid peroxidation. We previously demonstrated that F2-IsoPs levels in cerebrospinal fluid (CSF) of aSAH patients positively correlated with poor clinical conditions. In this work, we refined F4-NPs analysis and investigated the role of potential oxidative damage to neurons in aSAH patients by detecting F4-NPs in CSF. [2H4]-15-F2t-IsoP, rather than [18O2]-17-F4c-NP or [2H4]-PGF2α, was used as the internal standard for F4-NPs analysis. One problem of the use of [18O2]-17-F4c-NP was the potential interference resulting from F2-dihomo-IsoPs in CSF. CSF specimens of 15 aSAH patients for up to 10 days and those of 12 non-aSAH controls were analyzed. First day, mean, and peak levels of F4-NPs were all significantly higher in aSAH patients than in controls and correlated with the Fisher Scale and 3-month Glasgow Outcome Scale, but only mean levels of F4-NPs correlated with Hunt and Hess Grade. The results first demonstrate oxidative damage to DHA in brain tissue following aSAH and suggest that F4-NPs in CSF could be a better predictor for outcome of aSAH than F2-IsoPs at early time points.