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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：
10035049
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/10035049
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 Diet 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 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. .

项目总结