Intracranial aneurysms often remain asymptomatic until rupture, causing aneurysmal subarachnoid hemorrhage (aSAH). aSAH frequently leads to cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI), significantly increasing the risk of severe neurological deficits and mortality. Identifying reliable biomarkers, such as lipid peroxidation metabolites (LPMs), is crucial for early prediction and timely intervention. This study summarizes current knowledge on LPMs as potential biomarkers for CVS and DCI after aSAH. A systematic review was conducted following PRISMA guidelines. Two independent authors searched PubMed, Web of Science, and Scopus for articles studying the association between non-enzymatic and enzymatic lipid metabolites and CVS or DCI after aSAH. Quality and risk of bias were evaluated using the Newcastle-Ottawa Scale. Extracted data included metabolite concentrations, biological sample types, timing of collection, patient demographics, clinical severity of aSAH, Fisher's grade, DCI definition, and relationship to DCI. Of 519 records screened, 17 studies were included. Lipid metabolites were measured in blood (5 studies), cerebrospinal fluid (11 studies), and urine (2 studies). F2-isoprostanes (F2-IsoPs), studied in 7 articles, were linked to increased DCI risk, with elevated levels observed within three days post-aSAH. Isofurans (IsoFs) predicted DCI risk between days 5 and 8 post-aSAH, while elevated cholesteryl ester hydroperoxide (CEOOH) levels on day 2 linked to symptomatic vasospasm. Enzymatic arachidonic acid (AA) metabolites, including 6-keto-prostaglandin F1-α, prostaglandin D2, and leukotriene C4, were also associated with early DCI risk. To the best of our knowledge, this review is the first to comprehensively assess all LPMs in relation to CVS and DCI. Elevated concentrations of F2-IsoPs and enzymatic AA derivatives may serve as biomarkers for DCI prediction in aSAH. These findings highlight the need to explore the potential of LPMs, paving the way for risk stratification and timely interventions to improve patient outcomes and aid researchers in developing predictive scoring systems for DCI. Clinical trial number Not applicable.
Keywords: Biomarkers; Cerebral vasospasm; Delayed cerebral ischemia; Oxidative stress; Subarachnoid hemorrhage.
© 2025. The Author(s).