Distributed microstimulation for epilepsy

分布式微刺激治疗癫痫

基本信息

批准号：
7667763
负责人：
ROBERT E GROSS
金额：
$ 16.84万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-01 至 2010-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7667763
关键词：
Action Potentials Adherent Culture Affective Algorithms American Animal Model Architecture Attenuated Axon Back Behavioral Biomedical Engineering Brain Cell Culture Techniques Characteristics Cognitive Collaborations Complex Custom Data Disabled Persons Electric Stimulation Electrodes Electroencephalogram Epilepsy Excitatory Postsynaptic Potentials Feedback Frequencies Generations Goals Human Implant In Vitro Lead Measures Medical Methodology Methods Microelectrodes Modeling Monitor Neurons Operative Surgical Procedures Partial Epilepsies Patients Pattern Plague Population Preparation Property Rattus Recurrence Rodent Scientist Seizures System Testing Tissues Translating Translational Research Weight Work abstracting base brain electrical activity brain tissue design electric field electric impedance extracellular feeding in vivo microstimulation neuronal cell body novel novel strategies prevent public health relevance relating to nervous system success voltage

项目摘要

DESCRIPTION (provided by applicants): Abstract Uncontrolled epileptic seizures plague more than one million Americans, despite the best medical and surgical treatments available. Novel therapies are desperately needed. We have formed a productive collaboration between a biomedical engineer and a translational clinician-scientist to pioneer a novel approach to suppressing generation of seizures using direct closed-loop multielectrode microstimulation of the epileptic focus. The method is based on our exciting in vitro work in which epileptiform activity in neuronal cultures was completely blocked by low voltage, low frequency microstimulation, distributed across multiple electrodes. The goal of the present project is to translate these results in vivo. We have manufactured a novel custom-designed system to simultaneously stimulate and record from chronically implanted microelectrodes in a closed-loop feedback fashion. We will optimize the parameters and materials to effectively maintain the firing rate of neurons in the epileptic focus in a range from which bursts of action potential - which underlie epileptic seizures - are prevented from occurring. Our success will be measured by demonstrating modulation of electrographic (EEG) and behavioral seizure activity in our rat model of focal onset seizures. If successful, this work will lead to a new treatment for patients disabled by intractable focal onset seizures. PUBLIC HEALTH RELEVANCE: To treat intractable focal-onset epileptic seizures, we propose a novel approach in which electrical stimulation - continuously delivered to the epileptic focus through arrays of microelectrodes - is tuned to maintain neural activity in a range from which epileptic seizures cannot arise. In this approach, which is based on our ability to completely suppress epileptiform bursts of action potentials in a cell culture model, state-control methodology prevents seizures from arising, rather than attempting to abort seizures after they arise. This translational research in a rodent focal epilepsy model hopefully will lead to a much needed novel treatment for patients with disabling, intractable focal-onset seizures.

描述（由申请人提供）：尽管可用的医疗和手术治疗最好，但抽象的不受控制的癫痫发作遭受了超过一百万美国人的困扰。迫切需要新颖的疗法。我们已经在生物医学工程师和转化临床医生科学家之间建立了一种富有成效的合作，以使用一种新的方法来抑制癫痫焦点的直接闭环多电极微刺激。该方法基于我们令人兴奋的体外工作，在该工作中，神经元培养物中的癫痫样活性被低压，低频微刺激（分布在多个电极上）完全阻塞。本项目的目的是在体内翻译这些结果。我们已经制造了一种新型的定制设计系统，以闭环反馈方式同时刺激和记录了慢性植入的微电极。我们将优化参数和材料，以有效地维持癫痫焦点中神经元的发射速率，从而阻止了动作电位爆发的爆发（这些动作电位爆发）被阻止发生。我们的成功将通过证明对局灶性发作大鼠模型中电学（EEG）和行为癫痫活性的调节来衡量。如果成功，这项工作将导致针对顽固性局灶性发作癫痫发作残疾患者的新治疗方法。公共卫生相关性：为了治疗顽固性的焦点发作性癫痫发作，我们提出了一种新的方法，其中通过各种微电极阵列将电刺激（连续地传递至癫痫发生的焦点） - 以维持神经活动，以在其中癫痫发作的范围内保持癫痫发作。在这种方法中，这是基于我们完全抑制细胞培养模型中癫痫样爆发的作用电位爆发的能力，状态控制方法论可以防止癫痫发作，而不是试图在出现后尝试中止癫痫发作。在啮齿动物局灶性癫痫模型中的这项翻译研究有望为残疾，可怕的焦点发作性癫痫发作的患者提供急需的新颖治疗方法。