权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Rheoerythrocrine dysfunction in stroke and remote ischemic conditioning (REDS)

中风和远程缺血调节 (REDS) 中的红细胞分泌功能障碍

基本信息

批准号：
10565864
负责人：
DAVID C. HESS
金额：
$ 19.96万
依托单位：
AUGUSTA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-01 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10565864
关键词：
5&apos -AMP-activated protein kinase Accident and Emergency department Affect Ambulances Biological Markers Blinded Blood Blood Cells Blood Pressure Blood Vessels Blood flow Blood specimen Brain Cells Cerebrovascular Circulation Clinical Clinical Trials Controlled Clinical Trials Data Denmark Development Diameter Disabled Persons Disease Endothelial Cells Erythrocytes FDA approved Flow Cytometry Functional disorder Helicopter Hospitals Hypoxia Injury Ischemia Ischemic Stroke Limb structure Measures Microcirculation Mus NOS3 gene Nitrites Organ Outcome Oxygen Patients Pharmacodynamics Phase Plasma Play Pre-hospital setting Proteins Randomized Role SKIL gene Source Stroke Testing Therapeutic Traumatic Brain Injury Vasodilation Work acute stroke arm comorbidity conditioning endovascular thrombectomy functional improvement improved improved outcome indexing ischemic conditioning neuroprotection novel novel marker novel therapeutics outcome prediction pharmacodynamic biomarker post stroke pre-clinical response shear stress stroke clinical trials stroke patient stroke therapy stroke trials thrombolysis

项目摘要

Despite the efficacy of endovascular thrombectomy (ET), 50% of the patients remain disabled at 3 months. Adjunctive therapies to thrombolysis and ET are needed that provide “bridging neuroprotection” and improve collaterals. Remote ischemic conditioning (RIC), the simple and safe repetitive inflation-deflation of a blood pressure (BP) cuff on the limbs, improves collateral blood flow in acute stroke. RIC is now being tested in a large phase III randomized, sham-controlled, prehospital acute stroke trial of 1500 subjects in Denmark, the RESIST trial. While nitric oxide synthase 3 (NOS3) was thought restricted to endothelial cells, it is now known that red blood cells (RBCs) express NOS3 and that this erythrocyte NOS3 (eryNOS3) may play a critical role in microvascular blood flow and organ protection during ischemia. We have developed two putative “rheo- erythocrine” biomarkers: RBC deformability by ektacytometry and eryNOS3 by flow cytometry. Our hypothesis is that RBC deformability and eryNOS3 are “pharmacodynamic” biomarkers of RIC and will be related to improved outcome in acute stroke. To test this hypothesis we will utilize the clinical trial platform of the RESIST trial for a biomarker substudy. Our specific aims include: Aim 1: Determine if RIC improves rheoerythrocrine biomarkers (RBC deformability, increases activated eryNOS3) and/or increases plasma nitrite compared to sham RIC .Aim 2: Determine if rheo-erythrocrine biomarkers are related to improved short term (24 hr) or long term (90 day mRS) clinical outcome. We expect that RBC deformability and eryNOS3 will be biomarkers of the conditioning response (pharmacodynamic) and predictive of improved clinical outcome in stroke patients.

尽管血管内血栓切除术 (ET) 有效，但 50% 的患者在 3 个月后仍处于残疾状态。需要溶栓和 ET 的辅助疗法来提供“桥接神经保护”并改善抵押品。远程缺血调节 (RIC)，简单且安全的重复性血液充气-放气四肢压力 (BP) 袖带可改善急性中风时的侧支血流。 RIC 目前正在大规模测试 RESIST 在丹麦对 1500 名受试者进行了 III 期随机、假手术对照、院前急性卒中试验审判。虽然一氧化氮合酶 3 (NOS3) 被认为仅限于内皮细胞，但现在已知红色血细胞 (RBC) 表达 NOS3，这种红细胞 NOS3 (eryNOS3) 可能在缺血时的微血管血流和器官保护。我们开发了两种假定的“流变- “红分泌”生物标志物：通过 ektacytometry 测定红细胞变形能力，通过流式细胞术测定 eryNOS3。我们的假设红细胞变形能力和eryNOS3是RIC的“药效学”生物标志物，并且与改善急性中风的预后。为了验证这一假设，我们将利用 RESIST 的临床试验平台生物标志物亚研究试验。我们的具体目标包括：目标 1：确定 RIC 是否可以改善流红细胞分泌与假手术相比，生物标志物（红细胞变形性、激活的 eryNOS3 增加）和/或血浆亚硝酸盐增加 RIC 目标 2：确定流变红细胞生物标志物是否与短期（24 小时）或长期改善相关（90 天 mRS）临床结果。我们预计红细胞变形能力和 eryNOS3 将成为调节反应（药效学）并预测中风患者临床结果的改善。

项目成果

期刊论文数量（14）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Recycled Translation: Repurposing Drugs for Stroke.

DOI：
10.1007/s12975-022-01000-z
发表时间：
2022-12
期刊：
TRANSLATIONAL STROKE RESEARCH
影响因子：
6.9
作者：
Spellicy, Samantha E.;Hess, David C.
通讯作者：
Hess, David C.

Remote Ischemic Conditioning: Feasible and Potentially Beneficial for Ischemic Stroke.

DOI：
10.1001/jama.2022.13365
发表时间：
2022-08-16
期刊：
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
影响因子：
120.7
作者：
Hess, David C.;Blauenfeldt, Rolf A.;Andersen, Grethe
通讯作者：
Andersen, Grethe

Preclinical evaluation of circadian rhythm in ischemic stroke outcomes.

缺血性卒中结果中昼夜节律的临床前评估。

DOI：
发表时间：
2021
期刊：
Conditioning medicine
影响因子：
0
作者：
Kamat,PradipK;Khan,MohammadBadruzzaman;Wood,Kristofer;Siddiqui,Shahneela;Rudic,DanielR;Dhandapani,Krishnan;Waller,Jennifer;Hess,DavidC
通讯作者：
Hess,DavidC

The Immunomodulatory Capacity of Induced Pluripotent Stem Cells in the Post-stroke Environment.