MicroRNA Endotypes of Systemic Inflammation in Sub-Arachnoid hemorrhaGE (MESSAGE)

蛛网膜下腔出血全身炎症的 MicroRNA 内型 (MESSAGE)

• 批准号: 10704331
• 负责人: Sherry Hsiang-Yi Chou
• 金额: $ 18.2万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10704331
• 关键词: MicroRNA; Endotypes; Systemic; Inflammation; Sub

PROJECT SUMMARY Aneurysmal subarachnoid hemorrhage (SAH) is disproportionately lethal and morbid for young patients, causes extensive long-term disability, and results in significant health-economic burden to society. SAH is a heterogeneous condition. A unique feature of SAH is that, in addition to brain injury, patients can develop an acute and severe systemic illness with multiple extra-cerebral organ dysfunctions and a systemic inflammatory response syndrome. Several recent SAH clinical trials all failed to show therapeutic benefit partly due to the high degree of disease heterogeneity. A major barrier to a therapeutic breakthrough in SAH is the lack of appropriate biomarkers to identify patients most at risk for subsequent injury, complications, and bad outcome in this heterogenous population. Endotypes are biological subtypes defined by distinct pathophysiologic mechanisms that could be identified by corresponding biomarkers. Discovery of novel endotypes has led to major therapeutic breakthroughs in cancer and autoimmune diseases. MicroRNAs (miRs) are a novel class of molecules with ideal characteristics as potential biomarkers for systemic response to SAH because miRs are very stable in blood, very specific in their cells of origin and destination, can modulate biological processes in recipient cells by regulating gene expression, and are known to mediate inflammation and immune function. We have promising preliminary data showing that early increase in blood miR-26a after SAH is associated with favorable long-term outcome and possibly reduced risk for delayed cerebral ischemia (DCI), a major cause of morbidity. We hypothesize that blood miR-26a is an early biomarker for SAH long-term outcome and that miR-26a may modulate systemic inflammatory host response and reduce delayed cerebral ischemia (DCI). We propose to investigate miR-26a as a potential biomarker in an existing SAH patient cohort and biobank while simultaneously recruiting a separate, independent replication SAH cohort for prospective validation of this biomarker. As miRs may function in networks, we will explore the global blood miR transcriptome in a subset of patients to identify possible miR networks associated with SAH outcome and with DCI. To examine biological plausibility of miR- 26a in defining a novel inflammation endotype in SAH, we will explore the relationship between blood miR-26a expression and subsequent manifestations of clinical systemic inflammatory response syndrome and changes in blood inflammatory cytokine levels.

项目摘要 动脉瘤性蛛网膜下腔出血（SAH）在年轻患者中是不成比例的致命和病态， 广泛的长期残疾，给社会造成重大的健康经济负担。SAH是一个 非均质条件SAH的一个独特特征是，除了脑损伤外，患者还可以发展为 急性和严重的全身性疾病，伴有多种脑外器官功能障碍和全身性炎症 反应综合征最近的几项SAH临床试验均未能显示治疗益处，部分原因是 疾病高度异质性。SAH治疗突破的主要障碍是缺乏 适当的生物标志物，以识别最有可能发生后续损伤、并发症和不良结局的患者 在这个异质的群体中。 内型是由不同的病理生理机制定义的生物亚型，可以通过以下方式鉴定： 相应的生物标志物。新型内型的发现导致了癌症治疗的重大突破 和自身免疫性疾病。microRNA（miRs）是一类具有理想特性的新型分子， 因为miR在血液中非常稳定，在其表达中非常特异， 来源和目的细胞，可以通过调节基因表达来调节受体细胞中的生物过程， 并且已知介导炎症和免疫功能。我们有初步数据显示， SAH后血液miR-26 a的早期增加与良好的长期结局相关， 迟发性脑缺血（DCI）的风险，这是发病的主要原因。 我们假设血液中的miR-26 a是SAH长期预后的早期生物标志物，并且miR-26 a可能与SAH的预后有关。 调节全身炎症宿主反应并减少迟发性脑缺血（DCI）。我们建议 在现有SAH患者队列和生物库中研究miR-26 a作为潜在生物标志物，同时 招募一个单独的、独立复制的SAH队列，用于该生物标志物的前瞻性验证。作为最低限度反应 可能在网络中发挥作用，我们将探索患者子集中的整体血液miR转录组，以确定 可能与SAH结局和DCI相关的miR网络。为了检测miR-121的生物学可接受性， 在定义SAH中新的炎症内型时，我们将探讨血液miR-26 a与SAH中的炎症内型之间的关系。 临床全身炎症反应综合征的表达和后续表现及变化 血液中的炎症细胞因子水平。

项目成果

A Nail in The Brain: Delayed Traumatic Pseudoaneurysm.

大脑中的钉子：迟发性外伤性假性动脉瘤。

• DOI: 10.1007/s12028-019-00798-1
• 发表时间: 2020
• 期刊: Neurocritical care
• 影响因子: 3.5
• 作者: Vadamalai,Karthik;Hirzallah,MohammadI;Chou,SherryHsiang-Yi
• 通讯作者: Chou,SherryHsiang-Yi

Biospecimens and Molecular and Cellular Biomarkers in Aneurysmal Subarachnoid Hemorrhage Studies: Common Data Elements and Standard Reporting Recommendations.

• DOI: 10.1007/s12028-019-00725-4
• 发表时间: 2019-06
• 期刊: Neurocritical care
• 影响因子: 3.5
• 作者: Chou SH;Macdonald RL;Keller E;Unruptured Intracranial Aneurysms and SAH CDE Project Investigators
• 通讯作者: Unruptured Intracranial Aneurysms and SAH CDE Project Investigators

Proceedings of the First Curing Coma Campaign NIH Symposium: Challenging the Future of Research for Coma and Disorders of Consciousness.

• DOI: 10.1007/s12028-021-01260-x
• 发表时间: 2021-07
• 期刊: Neurocritical care
• 影响因子: 3.5
• 作者: Claassen J;Akbari Y;Alexander S;Bader MK;Bell K;Bleck TP;Boly M;Brown J;Chou SH;Diringer MN;Edlow BL;Foreman B;Giacino JT;Gosseries O;Green T;Greer DM;Hanley DF;Hartings JA;Helbok R;Hemphill JC;Hinson HE;Hirsch K;Human T;James ML;Ko N;Kondziella D;Livesay S;Madden LK;Mainali S;Mayer SA;McCredie V;McNett MM;Meyfroidt G;Monti MM;Muehlschlegel S;Murthy S;Nyquist P;Olson DM;Provencio JJ;Rosenthal E;Sampaio Silva G;Sarasso S;Schiff ND;Sharshar T;Shutter L;Stevens RD;Vespa P;Videtta W;Wagner A;Ziai W;Whyte J;Zink E;Suarez JI;Curing Coma Campaign
• 通讯作者: Curing Coma Campaign

Glycemic Gap Predicts in-Hospital Mortality in Diabetic Patients with Intracerebral Hemorrhage.

血糖差距可预测糖尿病脑出血患者的院内死亡率。

• DOI: 10.1016/j.jstrokecerebrovasdis.2021.105669
• 发表时间: 2021
• 期刊: Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
• 作者: Zarean,Elaheh;Lattanzi,Simona;Looha,MehdiAzizmohammad;Napoli,MarioDi;Chou,SherryH-Y;Jafarli,Alibay;Torbey,Michel;Divani,AfshinA
• 通讯作者: Divani,AfshinA