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）：摘要尽管有最好的医疗和手术治疗方法，但不受控制的癫痫发作仍然困扰着超过一百万美国人。迫切需要新的疗法。我们在生物医学工程师和转化临床医生科学家之间建立了富有成效的合作，开创了一种利用直接闭环多电极微刺激癫痫病灶来抑制癫痫发作的新方法。该方法基于我们令人兴奋的体外工作，其中神经元培养物中的癫痫样活动被分布在多个电极上的低电压、低频微刺激完全阻断。本项目的目标是将这些结果转化为体内。我们制造了一种新颖的定制设计系统，以闭环反馈方式同时刺激和记录长期植入的微电极。我们将优化参数和材料，以有效地将癫痫病灶中神经元的放电率维持在一定范围内，从而防止发生癫痫发作的动作电位爆发。我们的成功将通过在局灶性癫痫发作的大鼠模型中展示电图（EEG）和行为癫痫活动的调节来衡量。如果成功，这项工作将为因顽固性局灶性癫痫发作而致残的患者提供新的治疗方法。公共健康相关性：为了治疗难治性局灶性癫痫发作，我们提出了一种新方法，其中通过微电极阵列持续向癫痫病灶传递电刺激，以将神经活动维持在不会发生癫痫发作的范围内。在这种方法中，基于我们在细胞培养模型中完全抑制癫痫样动作电位爆发的能力，状态控制方法可以防止癫痫发作，而不是在癫痫发作发生后试图中止癫痫发作。这项啮齿动物局灶性癫痫模型的转化研究有望为患有致残、顽固性局灶性癫痫发作的患者带来急需的新型治疗方法。