Remote ischemic Conditioning Promotes Cerebrovascular Recovery after Intracerebral Hemorrhage

远程缺血调理促进脑出血后脑血管恢复

基本信息

批准号：
10240740
负责人：
KRISHNAN M. DHANDAPANI
金额：
$ 38.09万
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：
2020-09-01 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10240740
关键词：
5&apos -AMP-activated protein kinase Acute Affect Age American Anti-Inflammatory Agents Architecture Arteries Blood Pressure Blood Vessels Blood capillaries Bone Marrow Brain Brain Injuries Brain hemorrhage Canis familiaris Cells Cerebral Amyloid Angiopathy Cerebral Ischemia Cerebral hemisphere hemorrhage Cerebral small vessel disease Cerebrovascular Circulation Chronic Clinical Clinical Trials Cyclic AMP-Dependent Protein Kinases Development Drug Kinetics Endothelium Essential Fatty Acids Excision Exercise Exhibits Extracellular Matrix Proteins FDA approved Goals Hematoma Human Hypertension Immune Inflammation Intervention Intracranial Arterial Stenosis Ischemia Ischemic Stroke Limb structure Mediating Mediator of activation protein Medical Assistance Metabolic Mus Myelogenous Myeloid Cell Activation Myocardial Infarction Nervous System Physiology Neurologic Neurological outcome Neuroprotective Agents Nutrient Omega-3 Fatty Acids Outcome Pathway interactions Patients Phase I Clinical Trials Pre-Clinical Model Production Protein Kinase Proteins Quality of life Recovery Regulation Research Resolution Rupture Safety Stroke Subarachnoid Hemorrhage Survivors Testing Therapeutic Tissues Vascular Dementia Vascular remodeling angiogenesis arm arteriole blood vessel development cerebrovascular chromosome 1 loss clinical translation comorbidity cost effective dietary disability endothelial stem cell improved injured innovation ischemic conditioning limb ischemia macrophage mortality neovascularization neural network neurogenesis neurological recovery neurorestoration preservation repaired response restoration sex stem cells targeted treatment tissue repair translational study white matter injury

项目摘要

PROJECT SUMMARY Intracerebral hemorrhage (ICH), the most common form of hemorrhagic stroke, accounts for up to 15% of all strokes. ICH, which affects 67,000 Americans annually, induces the highest acute mortality and the worst long- term neurological outcomes of all types of stroke. Primary ICH is caused by the rupture of small vessels damaged by chronic hypertension or cerebral amyloid angiopathy. The resultant hematoma disrupts neural networks and damages the vascular architecture, culminating in a loss of brain function and the need for lifelong medical assistance. Re-establishment of a functional cerebrovascular network of small arteries and arterioles is a prerequisite for the removal of damaged tissue and for restoration of cerebral blood flow to deliver nutrients, trophic factors, and stem cells within the injured brain. Thus, there is a dire need for neurorestorative therapies that provide cerebrovascular recovery after ICH. Remote ischemic conditioning (RIC), the repetitive delivery of sub-lethal ischemia to a remote limb, demonstrated safety, versatility, and efficacy in early stage clinical trials; however, the utility of RIC after ICH remains understudied. The objective of this proposal is to test the overarching hypothesis that RIC induces vascular remodeling and improves long-term neurological function via anti-inflammatory myeloid cell activation after ICH. Specific Aim 1 will test the hypothesis that myeloid AMPKα1 mediates RIC-induced vascular repair after ICH. Specific Aim 2 will test the hypothesis that RIC increases angiogenesis via Del-1 release after ICH. Specific Aim 3 will test the hypothesis that delayed implementation of RIC improves chronic ICH outcomes in a sex- and age-independent manner. Expected outcomes of the proposed research include the identification of RIC as a clinically-safe, non-invasive intervention to promote cerebrovascular recovery after ICH. As ICH patients exhibit high permanent disability rates that diminish quality of life, our proposed research will identify a simple therapy to harness an endogenous pathway of neurological repair, providing an innovative and cost-effective approach to rehabilitate chronic ICH patients. .

项目概要脑出血 (ICH) 是出血性中风最常见的形式，占所有出血性中风的 15% 脑卒中每年影响 67,000 名美国人，导致最高的急性死亡率和最严重的长期死亡率。所有类型中风的术语神经学结果原发性脑出血是由受损的小血管破裂引起的。由慢性高血压或脑淀粉样血管病引起的血肿会破坏神经网络并损害血管结构，最终导致大脑功能丧失和需要终身医疗护理重建小动脉和小动脉的功能性脑血管网络是一种帮助。去除受损组织和恢复脑血流以输送营养的先决条件，因此，迫切需要神经恢复疗法。在 ICH 后提供脑血管恢复。远端肢体亚致死性缺血，在早期临床试验中证明了安全性、多功能性和有效性；然而，ICH 后 RIC 的效用仍未得到充分研究。本提案的目的是测试 RIC 诱导血管重塑并改善长期神经功能的总体假设 ICH 后通过抗炎性骨髓细胞激活特定目标 1 将检验骨髓细胞的假设。 AMPKα1 介导 ICH 后 RIC 诱导的血管修复。具体目标 2 将检验 RIC 的假设。 ICH 后通过 Del-1 释放增加血管生成特定目标 3 将检验延迟的假设。 RIC 的实施以与性别和年龄无关的方式改善慢性 ICH 结局。拟议研究的结果包括将 RIC 确定为一种临床安全、非侵入性的药物由于 ICH 患者表现出高度的永久性残疾，因此需要进行干预以促进 ICH 后的脑血管恢复。降低生活质量的比率，我们提出的研究将确定一种简单的疗法来利用内源性神经修复途径，为慢性脑出血的康复提供一种创新且具有成本效益的方法患者。。