Clinical Stimulation and Spreading Depolarization

临床刺激和扩散去极化

• 批准号: 10660795
• 负责人: Andrew Phillip Carlson
• 金额: $ 38.13万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10660795
• 关键词: Acute; Brain; Clinical; Clinical Trials; Coupled; Critical Care; Data; Early Mobilizations; Edema; Electrocorticogram; Electrodes; Electroencephalography; Event; Foundations; Future; Goals; Human; Hyperthermia; Hypotension; Hypotensives; Hypoxia; Infarction; Intensive Care Units; Intervention; Ischemia; Ischemic Stroke; Life; Link; Measurement; Metabolic; Metabolic stress; Monitor; Nervous System Trauma; Neurologic Examination; Outcome; Oxygen; Patient Care; Patients; Physical Stimulation; Physiological; Physiology; Public Health; Recovery; Research; Retrospective Studies; Risk; Risk Factors; Stroke; Subarachnoid Hemorrhage; Testing; Therapeutic; Therapeutic Intervention; Time; Tissues; Traumatic Brain Injury; Video Recording; Work; brain tissue; disability; hemodynamics; human subject; improved; improved outcome; insight; mortality; mouse model; novel; novel therapeutic intervention; post stroke; pre-clinical; preclinical study; preservation; standard of care; stroke model; stroke outcome; stroke patient; tactile stimulation; tissue oxygenation

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.

项目概要/摘要 临床刺激和生理波动是患者早期治疗的正常部分 严重中风。然而，情景刺激（诱导大脑激活）或生理刺激是可能的。 侮辱（例如低血压）实际上可能会通过引发破坏性的扩散去极化（SD）而造成伤害 脆弱大脑中的事件。这是基于 1) 最近对小鼠中风模型进行的临床前研究，2) 我们的 自己的初步数据表明此类事件与随后的 SD 相关，并且 3） 一项重大关键试验显示，接受早期活动的中风患者预后较差。这是 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 科目。当前的研究是我们长期目标的一部分，重点是了解机制， 急性神经损伤中与 SD 相关的后果和治疗方法。通过这个应用程序，我们 寻求确定重症监护病房的正常干预是否与风险增加相关 大面积半球中风患者感觉运动皮层的 SD 变化。我们将使用硬膜下评估这一点 皮层电图电极与邻近感觉运动区域的组织氧探针配对 需要进行去骨瓣减压术的大面积半球卒中患者的梗塞边界。我们将 然后进行长期视频脑电图记录以评估刺激事件并收集连续的 生理测量，所有时间均通过 SD 录音锁定。 SD 也将按照标准标准进行评分。 我们将评估更多的刺激事件或更多的短暂生理损伤是否与 SD 使用多种统计方法。这些分析将为了解这种情况是否存在提供基本见解。 事件可能引发 SD，预计会导致中风结果恶化。这样的发现将有 对患者有重要影响，特别是严重中风患者，早期积极活动已 已被证明会导致更糟糕的结果和更大的中风。如果更坏结果的机制 这些研究被证实与SD触发有关，那么这将为未来的研究奠定基础 努力减轻这些影响或以可持续发展为目标来改善结果。