Clinical Stimulation and Spreading Depolarization

项目摘要/摘要 临床刺激和生理波动是患者早期处理的正常部分 严重中风。然而，间歇性刺激(诱导大脑激活)或生理刺激是可能的 侮辱(如低血压)实际上可以通过触发破坏性的扩散除极(SD)而造成伤害 脆弱大脑中的事件。这是基于1)最近在中风小鼠模型上进行的临床前研究，2)我们的 自己的初步数据表明，这些事件与随后的SD有关，以及3) 一项主要的关键试验显示，接受早期活动的中风患者的预后更差。它是 因此，严格评估常规临床干预措施对人类SD的影响至关重要。 研究对象。目前的研究是我们长期目标的一部分，重点是了解这些机制， 急性神经损伤中与SD相关的后果和治疗方法。使用此应用程序，我们 寻求确定重症监护病房中的正常干预是否与风险增加相关 大半球卒中患者感觉运动皮质中的SD。我们将使用硬膜下评估这一点 皮质脑电图仪电极与组织氧探头配对位于感觉运动区邻近 需要去骨瓣减压术的大面积半球卒中患者的梗塞边缘。我们会 然后执行长期视频脑电记录，以评估刺激事件并收集连续 生理测量，所有时间与标清记录锁定。SD也将根据标准标准进行评分。 我们将评估更多的刺激事件或更多的暂时性生理侮辱是否与 SD使用了几种统计方法。这些分析将提供基本的见解，以了解这种 事件可能会引发SD，预计会导致中风结果恶化。这样的发现将会 对患者的重要意义，特别是严重中风患者，早期积极活动对 已被证明会导致更差的结果和更大的中风。如果更糟糕的结果发生在 这些研究被证实与SD的触发有关，这将为以后的研究提供基础 努力减轻这些影响或以SD为目标来改善结果。

PROJECT SUMMARY/ ABSTRACT Clinical stimulation and physiologic fluctuations are a normal part of the early management of patients with severe strokes. It is possible, however, that episodic stimulation (inducing brain activation) or physiologic insults (such as hypotension) could in fact cause harm by triggering damaging spreading depolarization (SD) events in vulnerable brain. This is based on 1) a recent pre-clinical study in a mouse model of stroke, 2) our own preliminary data suggesting that such events are associated with subsequent SD, and 3) results of a major pivotal trial that showed worse outcomes in stroke patients who received early mobilization. It is therefore critically important to rigorously assess the effects of routine clinical interventions on SD in human subjects. The current study is part of our long-term goals, focused on understanding the mechanisms, consequences, and therapeutic approaches related to SD in acute neurological injury. With this application, we seek to determine whether normal interventions in the intensive care unit are associated with an increased risk of SD in the sensorimotor cortex in patients with large hemispheric strokes. We will assess this using subdural electrocorticography electrodes paired with tissue oxygen probes in the sensorimotor region adjacent to the infarct border in patients with large hemispheric stroke who require decompressive hemicraniectomy. We will then perform long term video EEG recordings to assess for stimulation events and collect continuous physiological measurements, all time locked with SD recordings. SD will also be scored with standard criteria. We will these assess whether more stimulation events or more transient physiologic insults are associated with SD using several statistical approaches. These analyses will provide fundamental insights into whether such events could trigger SD, which is expected to result in worsening stroke outcomes. Such findings would have important implications for patients, particularly with severe stroke, where early aggressive mobilization has been demonstrated to result in worse outcomes and larger strokes. If the mechanism of worse outcomes in these studies is confirmed to be related to SD triggering, then this would provide the foundation for future efforts to mitigate these effects or target SD to improve outcomes.