Eicosanoid Ratios Predict the Development of Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage. (16th November 2020)

• Record Type: Journal Article
• Authors: Siler, Dominic A; Semonche, Alexa; Liu, Jesse J.X; Martini, Ross; Hinson, Holly; Cetas, Justin S
• Is Part Of: Neurosurgery. Volume 67(2010)Supplement 1
• Publication Date: 2020-11-16
• Subjects: Nervous system -- Surgery -- Periodicals; 617.48005
• DOI: 10.1093/neuros/nyaa447_256
• Languages: English
• ISSNs: 0148-396X

Abstract

Abstract: INTRODUCTION: Delayed cerebral ischemia (DCI) is a life-threatening complication of aneurysmal subarachnoid hemorrhage (SAH). The vasoactive P450 eicosanoids, 20-hydroxyeicosatetraenoic acid (20-HETE) and 14, 15-epoxyeicosatrienoic acid (14, 15-EET), are associated development of DCI after SAH and are thought to play opposing roles in DCI risk. METHODS: For preclinical studies, rats received intracisternal blood injections as a model of SAH. Hemorrhage severity was recorded as well as the ratio of 14, 15-EET/20-HETE in CSF. The blood flow response to cortical spreading depolarization was recorded as a surrogate for microvascular dysregulation. For clinical studies, CSF samples were drawn prospectively from SAH patients at multiple time points after admission. 20-HETE and 14, 15-EET levels in CSF samples were quantified using mass spectroscopy. RESULTS: Rats with greater hemorrhage severity had significantly lower median 14, 15-EET/20-HETE ratios compared to those with lesser or no hemorrhage. Patients who developed DCI had significantly lower median 14, 15-EET/20-HETE ratios compared to those who did not at both early and late time points (days 1–4: 0.0977 vs. 0.214; days 7–10: 0.317 vs. 0.961). A lower 14, 15 EET/20-HETE ratio within days 1–4 was associated with large-vessel vasospasm and worse outcome at discharge. CONCLUSION: Altered CSF 14, 15-EET/20-HETE ratios are driven, in part, by hemorrhage severity and may reflect a mechanistic dysfunction in microvascular tone that contributes to DCI. Further studies investigating CSF eicosanoids as therapeutic targets in SAH are warranted.