Seizure control by electric field control

通过电场控制进行咬合控制

• 批准号: 10641916
• 负责人: DOMINIQUE M DURAND
• 金额: $ 39.02万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10641916
• 关键词: Acute; Antiepileptic Agents; Brain; Characteristics; Chronic; Closure by clamp; Communication; Computer Models; Computer Simulation; Coupling; Data; Electrodes; Electrophysiology (science); Epilepsy; Extracellular Space; Focal Seizure; Furosemide; Generations; Goals; Hippocampus; Human; Image; In Vitro; Iron; Kainic Acid; Laboratories; Mediating; Membrane; Methodology; Methods; Modeling; Nerve Block; Neurons; Osmolar Concentration; Partial Epilepsies; Patients; Pharmaceutical Preparations; Play; Preparation; Recurrence; Research; Resistance; Rodent; Role; Seizures; System; Techniques; Technology; Temporal Lobe Epilepsy; Testing; Tissues; Travel; Treatment Efficacy; alternative treatment; design; efficacy testing; electric field; experimental study; extracellular; in vivo; neural; neuroimaging; neurotechnology; new technology; novel; novel strategies; novel therapeutics; optogenetics; prevent; recruit; voltage; voltage clamp

Abstract A seizure is an abnormal neural activity in the brain and the main characteristic of epilepsy. About one-third of the patients have seizures resistant to anti-epileptic medication and therefore, an alternative treatment is necessary. Recent studies show that neurons can be recruited and seizures can propagate by a mechanism known as electric field coupling. Our laboratory has shown that canceling the electric field in the extracellular space can prevent neural propagation and recruitment. We now propose to develop a novel neurotechnology that not only can control the propagation of seizures but prevent the seizure from being generated by controlling the extracellular electric field. With a combined methodology of in-vitro electrophysiology with state-of-the-art neural imaging, computer modeling and in-vivo preparations in rodents, we will implement the seizure control system and study its mechanism with four specific aims: 1) Prevent neuronal synchronization in hyperexcitable neural tissue, 2) Develop a novel technology of extracellular voltage clamp to control seizures in-vivo, 3) Determine the mechanisms of seizure control by an extracellular voltage clamp system, 4) Determine the role of the extracellular space in the clamping efficiency. Current electrical responsive control therapy detects a seizure and then applies stimulation. The proposed neurotechnology will prevent the synchronization between neurons to stop the generation of seizures before they arise at very low current amplitude thereby providing a novel therapeutic paradigm for treating epilepsy.

摘要 癫痫发作是大脑中的一种异常神经活动，也是癫痫的主要特征。大约三分之一的人 患者癫痫发作对抗癫痫药物有抵抗力，因此，另一种治疗方法是 这是必要的。最近的研究表明，神经元可以被招募，癫痫发作可以通过某种机制传播 这被称为电场耦合。我们的实验室已经证明，消除细胞外的电场 太空可以阻止神经的传播和招募。我们现在提议开发一种新的神经技术 不仅可以控制癫痫的传播，而且可以通过控制 胞外电场。采用体外电生理学和最新技术相结合的方法 在啮齿动物的神经成像、计算机建模和体内准备方面，我们将实施癫痫控制 系统研究其作用机制，有四个具体目的：1)防止过度兴奋的神经元同步化 神经组织，2)开发一种新的细胞外电压钳技术来控制体内癫痫发作，3) 确定细胞外电压钳系统控制癫痫发作的机制，4)确定 细胞外间隙对钳制效率的影响。目前的电反应控制疗法检测到癫痫发作 然后施加刺激。这项拟议的神经技术将阻止神经元之间的同步 在极低的电流幅度出现之前阻止癫痫的产生，从而提供了一种新的 治疗癫痫的治疗范例。