Psychosocial Stress and Behavioral Response to Stroke

描述(由申请人提供)：来自临床研究的大量证据表明，中风后的预后强烈地受到心理社会因素的影响。具有高水平社会支持或大型社会网络的患者在中风后表现出比社交孤立的人更快和更广泛的功能恢复。相比之下，感觉到的社会孤立会预测脑血管疾病的发病率和死亡率。同样的效果可以在动物身上重现；社会互动改善了实验性中风后的行为缺陷，减少了组织学损害，而社会隔离则增强了缺血性损害。调节社会环境、行为反应和疾病结果之间相互作用的机制尚不清楚。年龄越大，患包括脑血管疾病在内的许多慢性病的风险就越高。随着人口老龄化，中风的发病率和患病率将继续上升，导致我们社区中中风幸存者的数量不断增加。许多老年人面临着巨大的心理社会压力和孤立(失去配偶、抑郁、虚弱等)，然而，还没有研究探讨心理社会因素影响老年动物行为和结果的机制。我们将在社会隔离和配对居住的男性中使用短暂性局灶性脑缺血模型。我们将研究老化对隔离对中风损伤量、免疫反应和行为恢复的有害影响的贡献。外周和中枢免疫系统的组成部分将被检查和操纵。 公共卫生相关性：中风现在是美国残疾的主要原因。社会隔离预测脑血管疾病的发病率和死亡率。将在啮齿动物模型中研究调节社会环境、行为反应和疾病结果之间相互作用的机制。

DESCRIPTION (provided by applicant): Considerable evidence from clinical studies has shown that outcomes after stroke are strongly influenced by psychosocial factors. Patients with high levels of social support or large social networks exhibit more rapid and extensive functional recovery after stroke than socially isolated individuals. In contrast, perceived social isolation predicts morbidity and mortality from cerebrovascular disease. These same effects can be reproducibly demonstrated in animals; social interaction improves behavioral deficits and reduces histological damage after experimental stroke, whereas social isolation enhances ischemic damage. The mechanisms that mediate the interactions between the social environment, behavioral responses, and disease outcomes remain unclear. Advancing age is associated with an increased risk for the development of many chronic diseases including cerebrovascular disease. With our aging population, the incidence and prevalence of stroke will continue to rise, leading to increasing numbers of stroke survivors in our communities. Many older individuals are exposed to significant psychosocial stress and isolation (loss of spouse, depression, frailty etc.), however no studies have investigated the mechanisms by which psychosocial factors influence behavioral and outcomes in aged animals. We will utilize a transient focal ischemia model in socially isolated and pair housed males. We will examine the contribution of aging to the detrimental effects of isolation on the amount of stroke damage, the immune response, and behavioral recovery. Components of the peripheral and central immune system will be examined and manipulated. PUBLIC HEALTH RELEVANCE: Stroke is now the leading cause of disability in the United States. Social isolation predicts morbidity and mortality from cerebrovascular disease. The mechanisms that mediate the interactions between the social environment, behavioral responses, and disease outcomes will be studied in a rodent model.