Low-frequency stimulation of fiber tracts to control seizures

低频刺激纤维束以控制癫痫发作

基本信息

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
项目类别：
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

项目摘要

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.

抽象的癫痫是最普遍的神经系统疾病之一。癫痫经历的患者复发性癫痫发作可能导致各种症状，从光环到丧失意识。癫痫的特征是大量神经元和当前的治疗剂无法控制所有癫痫患者中25％的癫痫发作。我们有以前表明，一种针对纤维道的新型大脑刺激方法（fornix）而不是低频（1-20Hz）的灰质可有效抑制动物模型中的癫痫发作和中腹叶癫痫（MTLE）的患者。我们建议针对另一个突出的纤维道，call体（CC）抑制皮质癫痫发作并进行比较针对两种在高频刺激焦点刺激的现状方法的技术直接或丘脑的前核。具体来说，我们建议确定是否低频刺激CC可以通过选择性激活该局部癫痫发作来降低局灶性癫痫发作 CC纤维在急性模型（AIM 1）或癫痫病模型中支配重点与破伤风毒素（AIM 2）。然后，我们建议确定纤维道刺激是否可以改善与前刺激相比，由多个病灶产生的活性控制丘脑的核（AIM3）或慢性模型中的海藻酸（AIM4）。最后，我们将学习使用从动物中获得的维氏皮质脑切片的CC刺激机制先前的目标。该项目将与科学家，工程师和临床医生，如果成功的话，可以转化为一种新颖的患者特异性治疗方式用于控制顽固性癫痫患者的皮质癫痫发作。