Emsley Hedley C A, Smith Craig J, Tyrrell Pippa J, Hopkins Stephen J
Division of Neuroscience, The Walton Centre for Neurology and Neurosurgery, The University of Liverpool, Liverpool, L9 7LJ, UK.
Neurocrit Care. 2008;9(1):125-38. doi: 10.1007/s12028-007-9035-x.
Thrombolysis heralded a new era of acute intervention for ischemic stroke, accompanied by an increasing need for comprehensive acute critical care support. There remains the prospect of novel cerebral protection strategies. Cerebral ischemia initiates a complex cascade of events at genomic, molecular, and cellular levels, and inflammation is important in this cascade, both in the CNS and in the periphery. Closely linked events are induction of a classic acute phase protein response, activation of the hypothalamic-pituitary-adrenal axis (HPAA) and sympathetic nervous system (SNS), and rise in body temperature, all of which appear to importantly influence the outcome. Thrombolysis aside, various therapeutic strategies have been trialed without success recently, primarily directed at influencing neuronal activity and survival directly. Inflammation itself offers an attractive target, mainly because of its potential to exacerbate the spread of damage to the ischemic penumbra. A promising novel therapeutic approach is the interleukin-1 receptor antagonist (IL-1ra), which limits the action of the cytokine IL-1, a pivotal mediator in the pathophysiology of acute neurodegeneration. Critical care has much to offer some patients after acute ischemic stroke, including the delivery of acute interventions, often with very short therapeutic time windows, physiological support, and the management of complications. We discuss inflammation and its mediators in acute ischemic stroke, the systemic stress, and acute phase protein responses to acute ischemic stroke, how inflammation is relevant in deteriorating ischemic stroke, the impact of physiological variables, and both current and emerging interventions for acute ischemic stroke.
溶栓开启了缺血性卒中急性干预的新时代，同时对全面的急性重症监护支持的需求也与日俱增。新型脑保护策略仍有前景。脑缺血在基因组、分子和细胞水平引发一系列复杂事件，炎症在这一事件链中起着重要作用，在中枢神经系统和外周均是如此。紧密相关的事件包括经典急性期蛋白反应的诱导、下丘脑-垂体-肾上腺轴（HPAA）和交感神经系统（SNS）的激活以及体温升高，所有这些似乎都对预后有重要影响。除溶栓外，各种治疗策略最近试验均未成功，主要是直接针对影响神经元活动和存活。炎症本身提供了一个有吸引力的靶点，主要是因为它有可能加剧对缺血半暗带损伤的扩散。一种有前景的新型治疗方法是白细胞介素-1受体拮抗剂（IL-1ra），它能限制细胞因子IL-1的作用，IL-1是急性神经退行性病变病理生理学中的关键介质。重症监护能为急性缺血性卒中后的一些患者提供很多帮助，包括实施急性干预（通常治疗时间窗非常短）、生理支持以及并发症管理。我们讨论急性缺血性卒中中的炎症及其介质、全身应激以及对急性缺血性卒中的急性期蛋白反应、炎症在缺血性卒中恶化中的相关性、生理变量的影响以及急性缺血性卒中的当前和新兴干预措施。
