Department of Neuroscience, The Ohio State University, Columbus, OH 43210, USA.
Exp Neurol. 2012 Jan;233(1):33-9. doi: 10.1016/j.expneurol.2011.01.016. Epub 2011 Jan 28.
Stress is a universal experience for living organisms. Under many circumstances activation of the hypothalamic-pituitary adrenal (HPA) axis is an adaptive response to stress. However, when stress or HPA activation is prolonged or its timing immediately precedes or coincides with an ongoing neurodegenerative process, the results can be deleterious. A causal relationship among stress, HPA axis activity, and stroke outcome exists. Stress is one of many potential triggers of ischemic stroke and sustained elevations in glucocorticoids compromise neuronal survival following an ischemic attack. Indeed, glucocorticoid exposure is a critical determinant of stroke outcome; prior exposure to stress and elevated peri-ischemic glucocorticoid concentrations are associated with poor outcome among stroke patients and in rodent models of cerebral ischemia. Likely, stress and glucocorticoid exposure exacerbate stroke by sensitizing the neuroimmune response to ischemia; stroke induces an upregulation of pro-inflammatory cytokines which contributes to migration of leukocytes into cerebral tissue and neuronal death. Social isolation also appears to compromise stroke outcome through priming of the neuroimmune system. Among individuals who survive the stroke, residual inflammation is apt to further compromise quality of life via its effect on cognitive function and affect. A better understanding of the mechanisms through which stress and social environment modulate neuroimmune function could lead to improved treatment of stroke and other neurodegenerative diseases.
压力是生物体普遍经历的一种现象。在许多情况下，下丘脑-垂体-肾上腺 (HPA) 轴的激活是对压力的适应性反应。然而，当压力或 HPA 激活持续时间延长，或者其时间正好在正在进行的神经退行性过程之前或同时发生时，结果可能是有害的。压力、HPA 轴活动与中风结果之间存在因果关系。压力是缺血性中风的众多潜在触发因素之一，持续升高的糖皮质激素会损害缺血攻击后的神经元存活。事实上，糖皮质激素暴露是中风结果的一个关键决定因素；中风患者和大脑局部缺血的啮齿动物模型中，先前的压力暴露和升高的围缺血性糖皮质激素浓度与不良结果相关。可能是压力和糖皮质激素暴露通过使神经免疫反应对缺血敏感而加重中风；中风会诱导促炎细胞因子的上调，导致白细胞迁移到脑组织和神经元死亡。社会隔离似乎也通过神经免疫系统的启动来损害中风结果。在幸存的中风患者中，残留的炎症很可能通过其对认知功能和情绪的影响进一步损害生活质量。更好地了解压力和社会环境调节神经免疫功能的机制，可能会导致中风和其他神经退行性疾病的治疗得到改善。
