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Research Article | Open Access

Eicosanoid ratios are associated with hemorrhage severity and predict development of delayed cerebral ischemia following subarachnoid hemorrhage

Dominic A. Silera, Alexa M. Semonchea,b, Ravi Samathama, Jesse J. Liua, Ross P. Martinic, Nabil J. Alkayedc, Holly E. Hinsond, Justin S. Cetase( )
Department of Neurological Surgery, Oregon Health & Science University, 3303 SW Bond Ave, Portland, OR 97239, United States
Department of Neurosurgery, Rutgers Robert Wood Johnson, 1 Robert Wood Johnson Pl, New Brunswick, NJ 08901, United States
Department of Anesthesiology and Perioperative Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, United States
Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, United States
Department of Neurosurgery, University of Arizona, Tucson, AZ 85724 , United States
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Abstract

Delayed cerebral ischemia (DCI) is a life-threatening complication of aneurysmal subarachnoid hemorrhage (aSAH). The vasoactive P450 eicosanoids 20-hydroxyeicosatretraenoate (20-HETE) and 14,15-epoxyeicosatrenoate (14,15-EET) are associated with the development of DCI and may play opposing roles in DCI risk. We hypothesized that the ratio of these opposing eicosanoids in cerebrospinal fluid (CSF) is associated with hemorrhage severity and the risk of developing DCI after aSAH. In a preclinical model, rats received intracisternal blood injections to approximate aSAH. Hemorrhage severity, cerebral blood flow (CBF), cortical spreading depolarizations were recorded, and CSF eicosanoid levels were quantified using mass spectrometry. In a parallel clinical study, CSF samples were collected and analyzed prospectively from subjects with aSAH and outcomes were tracked. Preclinically, rats with greater hemorrhage severity had impaired CBF and lower median 14,15-EET/20-HETE ratios compared to those with lesser or no hemorrhage. In aSAH patients, the CSF 14,15-EET/20-HETE ratio was negatively correlated with hemorrhage grade on imaging. Patients who developed DCI had lower median 14,15-EET/20-HETE ratios compared to those without DCI. The CSF 14,15-EET/20-HETE ratio correlates with hemorrhage severity and may reflect a mechanistic underpinning of microvascular dysfunction that contributes to DCI. These results suggest that vasoactive eicosanoids may be a therapeutic target in aSAH.

Keywords

Cerebral ischemiaSubarachnoid hemorrhageEicosanoidsVasospasm14,15 epoxyeicosatrienoate (14,15-EET)20-Hydroxyeicosatetraenoate (20-HETE)

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Brain Hemorrhages
Volume 3 Issue 4,
December 2022
Pages 135-142
DOI: 10.1016/j.hest.2022.05.004
Cite this article:
Siler DA, Semonche AM, Samatham R, et al. Eicosanoid ratios are associated with hemorrhage severity and predict development of delayed cerebral ischemia following subarachnoid hemorrhage. Brain Hemorrhages, 2022, 3(4): 135-142. https://doi.org/10.1016/j.hest.2022.05.004

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Received: 15 April 2022
Revised: 09 May 2022
Accepted: 10 May 2022
Published: 18 May 2022
© 2022 International Hemorrhagic Stroke Association.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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