Impacts of the systemic milieu on stroke outcome

全身环境对卒中结果的影响

基本信息

批准号：
9264598
负责人：
Kunlin Jin
金额：
$ 18.25万
依托单位：
UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-05-01 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9264598
关键词：
Acute myocardial infarction Affect Age Age-associated memory impairment Aging Animals Biological Markers Blood Brain Brain Injuries Cardiac Myocytes Cell physiology Clinical Disease Employee Strikes Environment Exposure to Goals Haptoglobins Heart Hypertrophy Histology Human Impaired cognition Impairment Incidence Individual Infarction Injectable Intraperitoneal Injections Ischemic Stroke Knowledge Liver Longevity MicroRNAs Molecular Molecular Profiling Motor Mus Muscle Neurodegenerative Disorders Neurologic Deficit Organism Outcome Parabiosis Plasma Proteomics Quantitative Reverse Transcriptase PCR Rattus Recovery of Function Research Risk Factors Role Serum Source Spinal Cord Stem cells Stroke Testing Therapeutic Transfusion Translating United States Western Blotting Work age related age-related muscle loss aged cognitive function disability effective therapy exosome experimental study functional outcomes improved innovation intraperitoneal motor deficit motor impairment myogenesis neurobehavioral test neuron loss novel novel therapeutic intervention prevent protein expression repaired screening stroke recovery stroke treatment young adult

项目摘要

Abstract: Compelling evidence indicates that systemic factors in the blood profoundly reverse aging related impairments, as exposure of aged mice to young blood using parabiosis (an approach for exchanging systemic milieu) and/or transfusion is capable of rejuvenating stem cell function in muscle, liver, spinal cord and brain and improving cognitive function, and ameliorates cardiac hypertrophy. Very recent studies also showed that a healthy animal could extend life span of a partner exposed to a lethal treatment or disease. These findings suggest that systemic milieu of a healthy young partner may be beneficial for an aged organism. However, it is currently unknown whether a healthy systemic milieu contributes to functional recovery after ischemic stroke. Our preliminary study showed that intraperitoneal administration of young plasma into ischemic stroke rats significantly reduced infarct volume and ameliorated motor impairment, compared with vehicle group. On the contrary, intraperitoneal administration of old plasma into young ischemic rats worsened their brain injury and motor deficits. Using a proteomic approach, we identified several new factors affecting stroke recovery. Therefore, the central hypothesis of this proposal is that: (a) the neurological deficits after ischemic stroke in aged rats are reversible upon exposure to young systemic milieu and (b) the underlying mechanism is likely due to the altered levels of soluble systemic factors in the young and aged rats. Our SPECIFIC AIM is to determine the effect of young adult (3-month-old) and old (24-month-old) systemic environment on functional outcome of ischemic stroke rats, and identify the potential systemic factors affecting stroke recovery. The rationale for the proposed research is that successful completion of the proposed experiments will provide missing, fundamental knowledge regarding the impact of the systemic milieu on functional recovery of young and aged ischemic rats. Identifying beneficial and detrimental molecules from young and old blood may result in new and innovative approaches to prevent or treatment of a variety of aged-related diseases including stroke.

抽象的：令人信服的证据表明，血液中的全身因素可以深刻逆转与衰老相关的疾病。损害，因为老年小鼠使用联体共生（一种交换的方法）接触年轻的血液全身环境）和/或输血能够恢复肌肉、肝脏、脊髓中的干细胞功能脊髓和大脑，改善认知功能，并改善心脏肥大。最近研究还表明，健康的动物可以延长暴露于致命物质的伴侣的寿命。治疗或疾病。这些发现表明，健康的年轻伴侣的系统环境可能是对衰老的机体有益。然而，目前尚不清楚健康的系统环境是否有助于缺血性中风后的功能恢复。我们的初步研究表明腹腔注射年轻血浆给缺血性中风大鼠可显着减少梗塞与媒介物组相比，体积和运动障碍得到改善。相反，对年轻缺血大鼠腹腔注射旧血浆会加重其脑损伤，运动缺陷。使用蛋白质组学方法，我们确定了影响中风恢复的几个新因素。因此，本提案的中心假设是：（a）缺血后的神经功能缺损老年大鼠的中风在暴露于年轻的全身环境后是可逆的，并且（b）潜在的机制可能是由于年轻和老年大鼠中可溶性全身因子水平的改变所致。我们的具体目标是确定年轻人（3 个月大）和老年人（24 个月大）的效果全身环境对缺血性卒中大鼠功能结果的影响，并确定潜在的全身环境影响中风康复的因素。拟议研究的基本原理是成功完成拟议的实验将提供有关影响的缺失的基本知识全身环境对年轻和老年缺血大鼠功能恢复的影响。识别有益的和来自年轻人和老年人血液中的有害分子可能会产生新的和创新的方法预防或治疗包括中风在内的多种与老年相关的疾病。