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，血液中的全身因素与衰老有关损害，作为使用抛物线的老年小鼠暴露于年轻血液（一种交换方法）全身环境）和/或输血能够使肌肉，肝脏，脊柱中的干细胞功能恢复活力绳索和大脑，改善认知功能，并改善心脏肥大。非常最近研究还表明，健康的动物可以延长暴露于致命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老年生物有益。但是，目前尚不清楚健康的系统环境是否缺血性中风后有助于功能恢复。我们的初步研究表明腹膜内给予年轻血浆入缺血性卒中大鼠大鼠的梗塞显着降低了梗塞与车辆组相比，体积和改善运动障碍。相反，将旧血浆腹膜内施用到年轻的缺血大鼠中，使他们的脑损伤恶化，运动不足。使用蛋白质组学方法，我们确定了几个影响中风恢复的新因素。因此，该提议的核心假设是：（a）缺血后的神经缺陷暴露于年轻的系统环境和（b）基础时，年龄大鼠的中风是可逆的机制可能是由于年轻大鼠和老年大鼠的可溶性系统因素水平改变所致。我们的具体目的是确定年轻成年（3个月大）和老（24个月大）的影响缺血性中风大鼠功能结果的系统环境，并识别潜在的全身性影响中风恢复的因素。拟议研究的理由是成功完成拟议的实验将提供有关缺失的基本知识全身环境关于年轻和老年缺血大鼠的功能恢复。确定有益和年轻和老血的有害分子可能会导致新的和创新的方法防止或治疗各种老年相关疾病，包括中风。