Isofurans and isoprostanes as markers of delayed brain injury and mitochondrial dysfunction following aneurysmal subarachnoid hemorrhage. A prospective observational study

Introduction F2-Isoprostanes (F2-IsoPs) and Isofurans (IsoF), specific markers of lipid peroxidation in vivo, have been reported to be elevated and have prognostic implications following subarachnoid hemorrhage (SAH). Platelet activation and vasoconstriction are attributed to these compounds. Elevated IsoF: F2-IsoPs ratios have been previously suggested as indicative of mitochondrial dysfunction. In this small study we examined their performance as specific biomarkers for delayed brain injury (DBI) development following SAH. We also explored if evidence of mitochondrial dysfunction could be found in a cohort of SAH patients. Methods Eighteen patients with SAH and 7 controls with normal neuroimaging and CSF analysis results underwent CSF sampling and abstraction of clinical, demographic, and laboratory data. Samples (two) of CSF were collected on day 1 and once on days 5-8 post-bleed. F2-IsoP and IsoF assays were performed at Vanderbilt Eicosanoid Core Lab by gas chromatography/mass spectroscopy. Levels are expressed in median (IQR) for non-parametric data. Repeated sample measurement were compared using the Wilcoxon signed-rank test, whereas the Mann Whitney test was used for other non-parametric data. Results Mean age was 61.2 + 15.7 (SAH cases) vs. 47.6 + 10 (controls) years, and 80% of SAH patients were female. Median Hunt-Hess score was 3 (2-4) and modified Fisher scale 3 (3-4). Thirty nine percent of patients developed DBI. F2-IsoP were significantly higher in SAH cases than in controls [47.5 (30.2-53.5) vs. 26.0 (21.2-34.5) pg/mL]. No significant differences were observed in patients with or without DBI [41 (33.5-52) vs. 44 (28.5-55.5) pg/mL]. IsoF were elevated in the second CSF sample in 9 patients, but undetectable in the remainder cases and all controls. Patients who developed DBI had significantly higher IsoF than cases who did not [(57 (34-72) vs. 0 (0-34) pg/mL]. Patients who met criteria for delayed injury had a significantly higher IsoF: F2IsoPs ratio on the late CSF sample [1.03 (1-1.38) vs. 0 (0-0.52)]. Conclusions Preliminary findings from this study suggest that IsoF may represent a specific biomarker predicting DBI following SAH and provide possible evidence of CNS mitochondrial dysfunction in SAH. Future studies to further explore the value of IsoF as biomarkers of secondary brain injury and the contribution of mitochondrial dysfunction and ferroptosis to clinical outcomes following SAH seem warranted.