类二十烷酸比值与出血严重程度相关,可预测蛛网膜下腔出血后迟发性脑缺血的发展

IF 1.3 Q4 CLINICAL NEUROLOGY
Dominic A. Siler , Alexa M. Semonche , Ravi Samatham , Jesse J. Liu , Ross P. Martini , Nabil J. Alkayed , Holly E. Hinson , Justin S. Cetas
{"title":"类二十烷酸比值与出血严重程度相关,可预测蛛网膜下腔出血后迟发性脑缺血的发展","authors":"Dominic A. Siler ,&nbsp;Alexa M. Semonche ,&nbsp;Ravi Samatham ,&nbsp;Jesse J. Liu ,&nbsp;Ross P. Martini ,&nbsp;Nabil J. Alkayed ,&nbsp;Holly E. Hinson ,&nbsp;Justin S. Cetas","doi":"10.1016/j.hest.2022.05.004","DOIUrl":null,"url":null,"abstract":"<div><p>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<em>,</em> 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.</p></div>","PeriodicalId":33969,"journal":{"name":"Brain Hemorrhages","volume":"3 4","pages":"Pages 135-142"},"PeriodicalIF":1.3000,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589238X22000225/pdfft?md5=e788109266a6318eeac951f6abbeda4b&pid=1-s2.0-S2589238X22000225-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Eicosanoid ratios are associated with hemorrhage severity and predict development of delayed cerebral ischemia following subarachnoid hemorrhage\",\"authors\":\"Dominic A. Siler ,&nbsp;Alexa M. Semonche ,&nbsp;Ravi Samatham ,&nbsp;Jesse J. Liu ,&nbsp;Ross P. Martini ,&nbsp;Nabil J. Alkayed ,&nbsp;Holly E. Hinson ,&nbsp;Justin S. Cetas\",\"doi\":\"10.1016/j.hest.2022.05.004\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>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<em>,</em> 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.</p></div>\",\"PeriodicalId\":33969,\"journal\":{\"name\":\"Brain Hemorrhages\",\"volume\":\"3 4\",\"pages\":\"Pages 135-142\"},\"PeriodicalIF\":1.3000,\"publicationDate\":\"2022-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2589238X22000225/pdfft?md5=e788109266a6318eeac951f6abbeda4b&pid=1-s2.0-S2589238X22000225-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Brain Hemorrhages\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2589238X22000225\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Brain Hemorrhages","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2589238X22000225","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0

摘要

延迟性脑缺血(DCI)是动脉瘤性蛛网膜下腔出血(aSAH)的致命并发症。血管活性P450类二十烷酸20-羟基二十烷酸二糖酸酯(20-HETE)和14,15-环氧二十烷酸二糖酸酯(14,15- eet)与DCI的发生有关,并可能在DCI风险中发挥相反的作用。我们假设脑脊液(CSF)中这些相反的二十烷类化合物的比例与aSAH后出血严重程度和发生DCI的风险有关。在临床前模型中,大鼠接受腹腔内血液注射以近似aSAH。记录出血严重程度、脑血流(CBF)、皮质扩张性去极化,并用质谱法测定脑脊液类二十烷水平。在一项平行临床研究中,从aSAH患者收集脑脊液样本并进行前瞻性分析,并跟踪结果。临床前,与出血较少或无出血的大鼠相比,出血严重程度较大的大鼠CBF受损,中位14,15- eet /20-HETE比率较低。在aSAH患者中,脑脊液14,15- eet /20-HETE比值与影像学上的出血分级呈负相关。与没有DCI的患者相比,发生DCI的患者的中位14,15- eet /20-HETE比率较低。脑脊液14,15- eet /20-HETE比值与出血严重程度相关,可能反映了导致DCI的微血管功能障碍的机制基础。这些结果提示血管活性类二十烷可能是aSAH的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Eicosanoid ratios are associated with hemorrhage severity and predict development of delayed cerebral ischemia following subarachnoid hemorrhage

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.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Brain Hemorrhages
Brain Hemorrhages Medicine-Surgery
CiteScore
2.90
自引率
0.00%
发文量
52
审稿时长
22 days
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信