DISCHARGE-1: Depolarisations in ISChaemia after subarachnoid HAemoRrhaGE-1

细胞毒性水肿一词描述了大脑中神经元肿胀的“海啸”样过程，当被动阳离子穿过细胞膜的流入超过ATP依赖性钠泵活性，然后水流入时，就会引发这种过程。取决于招募额外泵活性的能力，细胞毒性水肿是否可逆。因此，细胞毒性水肿标志着从生命到神经元死亡的过渡，这些神经系统疾病在死亡率，发病率和经济成本方面给我们的社会带来最大的健康负担：中风和缺氧。弥散加权成像在临床上用于早期检测细胞毒性水肿，但不适合连续床旁监测。大量的实验工作已经确定，皮层扩散去极化（CSD）是导致和维持细胞毒性水肿的机制。最近已经开发了使用硬膜下电极条记录患者的CSD的技术。本文提出的前瞻性、多中心、诊断性研究将利用这一点对迟发性缺血性卒中进行实时诊断，迟发性缺血性卒中是卒中的一种模型疾病，因为它是在最初的蛛网膜下腔出血后几天在重症监护医生的眼睛下发生的。其目的是确定CSD并确定允许未来神经保护治疗分层的临界值。这将把CSD概念转化为临床实践，为治疗开发提供新的靶点，并为神经保护剂的概念验证研究提供一种新的类型，允许非常早期的选择性干预。

The term cytotoxic oedema describes the ‘Tsunami’-like process of neuronal swelling in the brain that is ignited when passive cation influx across the cellular membranes exceeds ATP-dependent sodium pump activity followed by water influx. Dependent on the capacity to recruit additional pump activity, the cytotoxic oedema is reversible or not. Thus, the cytotoxic oedema marks the transition from life to neuronal death in those neurological conditions that place the highest health burden on our society in terms of mortality, morbidity and economic costs: stroke and hypoxia. Diffusion-weighted imaging is clinically used for early detection of cytotoxic oedema but unsuitable for continuous bedside monitoring. Extensive experimental work has established that cortical spreading depolarisation (CSD) is the mechanism that causes and maintains the cytotoxic oedema. Technology has been developed recently to record CSDs in patients using subdural electrode strips. The here proposed prospective, multicentre, diagnostic study will make use of this for real-time diagnosis of delayed ischaemic stroke, a model disease for stroke since it develops under the eyes of the intensivist several days after the initial aneurysmal subarachnoid haemorrhage. It is aimed to characterise CSDs and determine a cut-off value that will allow future neuroprotective treatment stratification. This will translate the CSD concept into clinical practice, provide novel targets for treatment development and a novel type of proof of concept study on neuroprotectants that allows very early selective intervention.