Low-frequency stimulation of fiber tracts to control seizures

低频刺激纤维束以控制癫痫发作

• 批准号: 10517517
• 负责人: DOMINIQUE M DURAND
• 金额: $ 33.45万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-12-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10517517
• 关键词: 4-Aminopyridine; Acute; Animal Model; Animals; Anterior; Auras; Bilateral; Brain; Cell Nucleus; Chronic; Collaborations; Commissure; Corpus Callosum; Deep Brain Stimulation; Development; Electric Stimulation; Electrodes; Engineering; Epilepsy; Excision; Fiber; Focal Seizure; Frequencies; Generalized seizures; Hippocampus; In Vitro; Injections; Intractable Epilepsy; Kainic Acid; Limbic System; Location; Methods; Modality; Modeling; Monitor; Motor Cortex; Neurons; Operative Surgical Procedures; Partial Epilepsies; Patients; Pharmaceutical Preparations; Pharmacology; Phase I Clinical Trials; Preparation; Procedures; Protocols documentation; Published Comment; Quality of life; Recurrence; Resected; Rest; Scientist; Seizures; Side; Site; Slice; Symptoms; Technology; Temporal Lobe Epilepsy; Testing; Tetanus Toxin; Thalamic structure; Therapeutic; Therapeutic Agents; Thick; Translating; Unconscious State; Work; clinical translation; commercialization; comparative efficacy; experience; gray matter; improved; in vivo; nervous system disorder; novel; phase II trial; prevent; voltage

Abstract Epilepsy is one of the most prevalent neurological disorders. Patients with epilepsy experience recurrent seizures that can cause a variety of symptoms ranging from auras to loss of consciousness. Epilepsy is characterized by the abnormal firing of large numbers of neurons and current therapeutic agents cannot control seizures in 25% of all epileptic patients. We have previously shown that a novel brain stimulation method targeting fiber tracts (fornix) instead of grey matter at low frequency (1-20Hz) is effective to suppress seizures in animal models and patients with mesial temporal lobe epilepsy (MTLE). We propose to target another prominent fiber tract, the corpus callosum (CC) to suppress cortical seizures and to compare this technology to two state-the-art methods that stimulate at high frequency either the focus directly or the anterior nucleus of the thalamus. Specifically, we propose to determine if stimulation of the CC at low frequency can decrease focal seizures by selectively activating the CC fibers innervating the focus in an acute model (Aim 1) or in focal chronic model of epilepsy with tetanus toxin (Aim 2). We then propose to determine if fiber tract stimulation can improve seizure control of activity generated by multiple foci compared to stimulation of the anterior nucleus of the thalamus (Aim3) or with kainic acid in chronic model (Aim4). Finally, we will study the mechanisms of the CC stimulation using in-vitro cortical brain slices obtained from animals in previous aims. The project will be carried with a collaboration between scientists, engineers and clinicians and if successful could be translated into a novel patient-specific therapeutic modality for the control of cortical seizures in patients with intractable epilepsy.

摘要