Antiepileptogenesis by Transcranial Magnetic Stimulation

经颅磁刺激抗癫痫发生

基本信息

批准号：
8062000
负责人：
Alexander Rotenberg
金额：
$ 17.33万
依托单位：
BOSTON CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-04-01 至 2012-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8062000
关键词：
Acute Affect Animal Model Animals Anticonvulsants Antiepileptogenic Attention Brain Cell Death Chronic Chronic Phase Clinical Collection D Glutamate DNA Fragmentation Data Doctor of Medicine Doctor of Philosophy Down-Regulation Electric Stimulation Electroencephalography Electromagnetics Epilepsy Epileptogenesis Evaluation Event FDA approved FOS gene Frequencies Future Glutamate Receptor Goals Hippocampus (Brain)Human In Situ In Vitro Injection of therapeutic agent Interneurons Investigation Isoxazoles Label Lead Literature Long-Term Depression Long-Term Potentiation Methods Modality Modeling Molecular Mechanisms of Action Monitor N-Methylaspartate Neuronal Injury Neurons Painless Pathologic Patients Peripheral Nerve Stimulation Phase Physiologic pulse Physiology Process Property Propionic Acids Protein Dephosphorylation Protocols documentation Pyramidal Cells Rattus Recurrence Research Role Seizures Slice Staging Status Epilepticus Stimulus Surface Synapses Testing Therapeutic Training Transcranial magnetic stimulation Work base brain tissue cell injury in vivo kainate magnetic field mossy fiber neuropsychiatry novel therapeutics prevent prophylactic receptor repetitive transcranial magnetic stimulation research study tool

项目摘要

DESCRIPTION (provided by applicant): Status epilepticus (SE) is often the triggering event for epileptogenesis, a sequence of neuronal changes that lead to abnormal excitation and ultimately to epilepsy. Epileptogenesis is dependent in large part on lasting enhancement of excitatory synaptic strength that is similar to the long-term potentiation (LTP) seen with experimental high frequency repetitive neuronal stimulation. In this regard, we propose to investigate the anti-epileptogenic potential of transcranial magnetic stimulation (IMS), a noninvasive method for repetitive neuronal activation that is coming to attention as a new therapeutic tool in epilepsy. The attractive properties of TMS are its ability to 1) terminate seizures and to 2) produce a lasting decrease in synaptic strength. The latter effect may be similar to the long-term depression (LTD) that is LTP's inhibitory counterpart. Accordingly, our overall hypothesis is that the anticonvulsive and LTD-like effects of low frequency repetitive (rTMS) can interfere with SE-triggered epileptogenesis and prevent the expression of epilepsy. TMS is based on the principle of electromagnetic induction where intracranial stimulating currents are generated by a strong extracranial magnetic field. TMS is safe, painless and inexpensive. Its anticonvulsive capacity is demonstrated in a small number of human trials showing a reduction seizure frequency reduction in epileptic patients treated with rTMS. However, its mechanism of action is poorly understood. Therefore, this developing field would benefit from animal model research for elucidation of basic TMS physiology, and for evaluation of its therapeutic potential. We recently developed methods for simultaneous TMS and electroencephalography (EEG) in seizing rats, and identified new potent anti-convulsive effect. We now propose to use the rat kainate (KA) SE model to test the capacity of TMS to 1) stop SE and prevent the seizure-associate neuronal injury, and 2) prevent SE-triggered epileptogenesis. Further, to evaluate the TMS-related cellular and molecular mechanisms of action, we will test whether low frequency rTMS can induce LTD by extending our methods to in vitro hippocampal slice recording. To achieve these overall goals, we will extend our studies to include in vitro and ex vivo hippocampal slice recordings.

描述（由申请人提供）：状态癫痫症（SE）通常是癫痫发生的触发事件，这是导致异常激发并最终导致癫痫病的一系列神经元变化。癫痫发生在很大程度上取决于持续增强的兴奋性突触强度，这与实验高频重复性神经元刺激相似。在这方面，我们建议研究经颅磁刺激（IMS）的抗癫痫发作潜力，这是一种无创的重复神经元激活的方法，它正引起人们对癫痫中一种新的治疗工具的关注。 TMS的吸引力是其能够1）终止癫痫发作的能力，而2）突触强度持续下降。后一种效应可能类似于LTP的抑制作用的长期抑郁（LTD）。因此，我们的总体假设是，低频重复（RTMS）的抗惊厥和LTD样效应会干扰SE触发的癫痫发生并防止癫痫的表达。 TMS基于电磁诱导的原理，其中颅内刺激电流由强颅外磁场产生。 TMS安全，无痛且便宜。在少数人类试验中证明了它的抗惊厥能力，表明用RTMS治疗的癫痫患者的癫痫发作频率降低。但是，其作用机理知之甚少。因此，这种发展的领域将受益于动物模型研究，以阐明基本TMS生理学，并评估其治疗潜力。我们最近开发了同时进行TMS和脑电图（EEG）的方法，并确定了新的有效的抗惊厥作用。现在，我们建议使用大鼠海藻（KA）SE模型测试TMS对1）停止SE的能力并防止癫痫发作缔合性神经元损伤，2）防止SE触发的癫痫发生。此外，为了评估与TMS相关的细胞和分子作用机制，我们将测试低频RTMS是否可以通过将我们的方法扩展到体外海马切片记录来诱导LTD。为了实现这些总体目标，我们将扩展研究以包括体外和离体海马切片记录。