Impacts of the systemic milieu on stroke outcome

摘要： 令人信服的证据表明，血液中的系统性因素在很大程度上逆转了衰老 损伤，如使用异种共生使老年小鼠暴露在年轻血液中(一种交换方法 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 改善认知功能，改善心肌肥厚。非常近 研究还表明，一只健康的动物可以延长接触致命病毒的配偶的寿命。 治疗或疾病。这些发现表明，健康的年轻伴侣的全身环境可能是 对衰老的生物体有益。然而，目前尚不清楚是否有一个健康的全身环境 有助于缺血性中风后的功能恢复。我们的初步研究表明 缺血性卒中大鼠腹腔注射青年血浆可显著减少脑梗塞 与赋形剂组比较，大鼠运动功能障碍明显减轻。相反地, 幼年脑缺血大鼠腹腔注射老年血浆可加重脑损伤和脑损伤 运动障碍。利用蛋白质组学方法，我们确定了几个影响中风康复的新因素。 因此，这一建议的中心假设是：(A)缺血后的神经功能障碍 老年大鼠卒中是可逆的，暴露在年轻的全身环境和(B)潜在的 其机制可能是由于幼年和老年大鼠体内可溶性系统因子水平的改变。 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局的影响 影响卒中康复的因素。这项拟议研究的理由是成功完成 所提议的实验将提供关于 全身环境对青年和老年脑缺血大鼠功能恢复的影响。确定有益的和 来自年轻人和老年人血液的有害分子可能会导致新的和创新的方法 预防或治疗各种与衰老有关的疾病，包括中风。

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.