Treatment of status epilepticus: a translational proposal.

癫痫持续状态的治疗：一项转化建议。

• 批准号: 8763864
• 负责人: CLAUDE G WASTERLAIN
• 金额: --
• 依托单位: VA GREATER LOS ANGELES HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2017-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8763864
• 关键词: Behavioral; Blood - brain barrier anatomy; Brain; Cardiac Surgery procedures; Cells; Chemicals; Complication; Conscious; Cool-X-A; Data; Drug Combinations; Effectiveness; Electroconvulsive Shock; Electroencephalography; Encephalopathies; Epilepsy; Epileptogenesis; Experimental Models; Exposure to; Grant; Head; Heart Arrest; Hippocampus (Brain); Inflammation; Intensive Care; Intensive Care Units; Life Support Systems; Lithium; Measures; Mediating; Methodology; Methods; Midazolam; Modeling; Monitor; Morbidity - disease rate; Neonatal; Neuronal Injury; Operative Surgical Procedures; Outcome; Parietal Lobe; Pathology; Patients; Perforant Pathway; Pharmaceutical Preparations; Pharmacotherapy; Pilocarpine; Recovery; Recurrence; Refractory; Seizures; Series; Severities; Status Epilepticus; Surface; Technology; Temperature; Testing; Time; Traumatic Brain Injury; Veterans; alternative treatment; cell mediated immune response; cooperative study; improved; morris water maze; mortality; natural hypothermia; neonatal hypoxic-ischemic brain injury; neurosurgery; prevent; public health relevance

DESCRIPTION (provided by applicant): PROJECT SUMMARY This project proposes to study hypothermia as a treatment of refractory status epilepticus (RSE). RSE is an increasingly common problem in VA Intensive Care Units. This may be due to improvement in life support systems and ICU technology, to increased availability of EEG recordings and increased recognition of "subtle" status epilepticus (SE) and other factors. The results of treatment of RSE are very poor, with high mortality and morbidity. New treatments are needed. Deep hypothermia (200 C) is used clinically during cardiac surgery and neurosurgery. Moderate hypothermia (32-330 C) is used routinely in the treatment of neonatal hypoxic- ischemic encephalopathy, of post-cardiac arrest encephalopathy and of traumatic brain injury. Hypothermia has proved safe and effective in those conditions. It has also been shown to inhibit seizure activity. Yet, it is rarely used to treat RSE, and we lack a basic understanding of its indications and effectiveness in RSE. We will test the hypothesis that deep hypothermia reduces seizure activity in two models of experimental status epilepticus induced respectively by chemical (lithium and pilocarpine) or by electrical (perforant path) stimulation of the brain. We will compare deep and mild hypothermia, and will test different durations of mild hypothermia, to find out whether longer durations of mild hypothermia can be as effective in terminating RSE as short durations of deep hypothermia. We will compare two methods for delivering hypothermia: whole body cooling and head cooling ("cool cap"). For the same level of cooling of parietal cortex, we expect whole body cooling is more effective than the "cool cap" method in terminating SE. Finally, we will study the effect of hypothermia treatment on the long-term consequences of RSE: neuronal injury, blood-brain barrier breakdown, cell-mediated inflammation, epileptogenesis and behavioral deficits. We expect hypothermia treatment to reduce all of these complications. At the end of this study, we expect to be able to define the depth, duration and method of hypothermia that is most effective in the treatment of experimental status epilepticus.

描述（由申请人提供）： 本项目旨在研究低温治疗难治性癫痫持续状态（RSE）。RSE是VA重症监护病房中越来越常见的问题。这可能是由于生命支持系统和ICU技术的改进，EEG记录的可用性增加以及对“微妙”癫痫持续状态（SE）和其他因素的认识增加。RSE的治疗效果很差，死亡率和发病率很高。需要新的治疗方法。深低温（200 ℃）在心脏手术和神经外科手术中被临床使用。中度低温（32-330 ℃）通常用于治疗新生儿缺氧缺血性脑病、心脏骤停后脑病和创伤性脑损伤。低温已被证明在这些条件下安全有效。它也被证明可以抑制癫痫发作。然而，它很少用于治疗RSE，我们缺乏对RSE的适应症和有效性的基本了解。我们将在两种实验性癫痫持续状态模型中检验深低温降低癫痫发作活动的假设，这两种模型分别由化学（锂和毛果芸香碱）或电（穿通通路）刺激诱导。 大脑我们将比较深低温和轻度低温，并将测试不同持续时间的轻度低温，以找出是否更长的持续时间的轻度低温可以有效地终止RSE作为短时间的深低温。我们将比较两种降低体温的方法：全身冷却和头部冷却（“冷却帽”）。对于顶叶皮层的相同冷却水平，我们预计全身冷却在终止SE方面比“冷却帽”方法更有效。最后，我们将研究低温治疗对RSE长期后果的影响：神经元损伤，血脑屏障破坏，细胞介导的炎症，癫痫发生和行为缺陷。我们希望低温治疗能减少所有这些并发症。在这项研究的最后，我们希望能够确定在实验性癫痫持续状态的治疗中最有效的低温的深度，持续时间和方法。