Detection and Control of Epilepsy

癫痫的检测和控制

• 批准号: 8139519
• 负责人: DOMINIQUE M DURAND
• 金额: $ 7.05万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8139519
• 关键词: 4-Aminopyridine; Adult; Affect; Animal Model; Animal Testing; Animals; Antiepileptic Agents; Axon; Brain; Breeding; Cell Nucleus; Cells; Chronic; Collaborations; Conflict (Psychology); Contralateral; Deep Brain Stimulation; Detection; Development; Diagnosis; Dimensions; Drug resistance; Dyes; Effectiveness; Electric Stimulation; Electrical Stimulation of the Brain; Electrodes; Electrophysiology (science); Engineering; Epilepsy; Excision; Fiber; Free Will; Frequencies; Gene Mutation; Genetic; Genetic Models; Goals; Hippocampus (Brain); Human; Image; In Vitro; Laboratories; Literature; Location; Long-Term Depression; Measures; Memory; Methods; Microelectrodes; Modality; Modeling; Movement Disorders; Mus; Muscle; Mutation; Neuraxis; Neurons; Operative Surgical Procedures; Outcome; Outcomes Research; Parkinson Disease; Partial Epilepsies; Pathway interactions; Patients; Pharmaceutical Preparations; Physiologic pulse; Picrotoxin; Population; Potassium Channel Blockers; Preparation; Prosthesis; Rattus; Recurrence; Relative (related person); Research; Research Personnel; Seizures; Side; Slice; Societies; Sodium Channel; Symptoms; Synaptic Transmission; Syndrome; Technology; Temporal Lobe; Temporal Lobe Epilepsy; Testing; Therapeutic; Therapeutic Agents; Tissues; Transgenic Mice; Unconscious State; base; clinical application; cost; design; experience; implantation; in vitro testing; in vivo; in vivo Model; innovation; insight; nervous system disorder; neural prosthesis; neuronal cell body; neuroprosthesis; neurotechnology; novel; novel strategies; postnatal; prevent; public health relevance; relating to nervous system; research study; synaptic depression; tool; voltage

DESCRIPTION (provided by investigator): Epilepsy is one of the most prevalent neurological disorder. Patients with epilepsy experience recurrent seizures that can cause a variety of symptoms ranging from muscle stiffness to loss of consciousness. Partial epilepsy is the most common syndrome in adult epilepsy patients and mesial temporal lobe epilepsy (MTLE) is the most common form of partial epilepsy. Epilepsy is characterized by the abnormal synchronization of large numbers of neurons. Current therapeutic agents cannot control seizures in 25% of all epileptic patients. Although electrical stimulation of the brain has been very effective to suppress some symptoms of Parkinson's disease, the level of seizure suppression by stimulation has been limited. The reason for this low therapeutic outcome could be attributed to an inadequate target for stimulation, lack of understanding of the mechanisms and non-optimum stimulation parameters. We propose to develop a method to suppress seizures by applying electrical stimulation to the commissural fiber tract that innervates both hippocampi (major epileptogenic foci in MTLE) from a single electrode location. Specifically, we propose to 1) evaluate the effect of low frequency stimulation 2) determine the effect of high frequency stimulation 3) study the mechanisms of the effect of stimulation, 4) analyze the spatial extent of the suppression/excitation effect in an intact hippocampal in-vitro preparation and 5) suppress seizures in a drug-free genetic model of epilepsy in mice. Current therapeutic agents are incapable of controlling seizure activity in 25% of all epileptic patients. The results of this neuro-technology project should provide valuable insights into the mechanisms underlying seizure suppression with electrical stimulation as well as establishing the preliminary design for an effective neural prosthesis for the control of seizures in patients with epilepsy. PUBLIC HEALTH RELEVANCE: About 3 million people have been diagnosed with epilepsy and the cost to the society is about $12.5B/year. Yet, only 25% of patients can receive some therapeutic benefits from anti-epileptic medication. We propose to develop an alternative therapeutic modality to surgical resection that relies on electrical stimulation of the brain to control seizures.

描述（由研究者提供）：癫痫是最常见的神经系统疾病之一。癫痫患者反复发作，可引起各种症状，从肌肉僵硬到意识丧失。部分性癫痫是成人癫痫患者中最常见的综合征，而内侧颞叶癫痫（MTLE）是部分性癫痫最常见的形式。癫痫的特点是大量神经元异常同步。目前的治疗药物不能控制25%的癫痫患者的癫痫发作。虽然脑电刺激对抑制帕金森病的某些症状非常有效，但刺激抑制癫痫发作的程度有限。这种低治疗效果的原因可能是刺激靶点不充分，缺乏对机制的理解和非最佳刺激参数。我们建议开发一种方法，通过从单个电极位置对支配两个海马（MTLE的主要致痫灶）的交联纤维束施加电刺激来抑制癫痫发作。具体而言，我们建议：1)评估低频刺激的效果；2)确定高频刺激的效果；3)研究刺激作用的机制；4)分析完整海马体外制备中抑制/兴奋效应的空间范围；5)在小鼠癫痫无药遗传模型中抑制癫痫发作。目前的治疗药物不能控制25%的癫痫患者的发作活动。这项神经技术项目的结果将为电刺激抑制癫痫发作的机制提供有价值的见解，并为有效控制癫痫患者癫痫发作的神经假体建立初步设计。公共卫生相关性：约有300万人被诊断患有癫痫，每年给社会造成的损失约为125亿美元。然而，只有25%的患者可以从抗癫痫药物中获得一些治疗效果。我们建议开发一种替代手术切除的治疗方式，依靠脑电刺激来控制癫痫发作。