Adaptive control of epileptic seizures using a genetically encoded sensor

使用基因编码传感器自适应控制癫痫发作

• 批准号: 8445212
• 负责人: Assaf A Gilad
• 金额: $ 31.2万
• 依托单位: HUGO W. MOSER RES INST KENNEDY KRIEGER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8445212
• 关键词: Acids; Adverse effects; Affect; Agreement; Animal Model; Anterior Nuclear Group; Antiepileptic Agents; Area; Bilateral; Brain; Brain Diseases; Calcium; Catfish; Cells; Chronic; Complex; Coupled; Data; Development; Devices; Electrodes; Electronics; Engineering; Epilepsy; Experimental Animal Model; Experimental Models; Frequencies; Funding; Glass; Goals; Hippocampus (Brain); Human; Implant; Interneurons; Lead; Methods; Neuronal Plasticity; Neurons; Oocytes; Operative Surgical Procedures; Organ; Patients; Population; Power Sources; Probability; Proteins; Radio; Rattus; Reporting; Seizures; Severities; Signal Transduction; Syndrome; System; Techniques; Technology; Temporal Lobe Epilepsy; Testing; Therapeutic; Time; Viral Vector; Xenopus laevis; base; brain surgery; directed evolution; efficacy testing; expression cloning; hippocampal pyramidal neuron; kainate; magnetic field; minimally invasive; nervous system disorder; new technology; novel; optical imaging; promoter; sensor; tool

DESCRIPTION (provided by applicant): About 35% of epileptic patients do not respond to antiepileptic drugs. Of these, only a quarter of them can be treated by resective surgery. Patients who have seizures arising from eloquent cortex, or which are multi-focal, bilateral or generalized are not candidates for resective surgery. For these patients, one currently available therapy is neurostimulation via electrodes. Neurostimulation reduces the probability of seizure occurrence and propagation either by manipulating remote control systems or by interfering with the epileptogenic zone itself. Recent evidence suggests that epileptic seizures in humans may be better controlled with adaptive (closed-loop), i.e. seizure-triggered stimulation. This requires a complex setup that integrates an implanted stimulation device coupled with real-time analysis techniques. Indeed, recent studies demonstrate that closed-loop stimulation in patients effectively decrease seizure frequency and severity. However, this invasive approach suffers from the need to implant complex, large and expansive electronic devices which depend on an external power supply, the need for major and sometimes repetitive brain surgeries and the unexpected and undesirable side effects that the actual placement of the neurostimulation electrodes often produces. We aim to develop an alternative, minimally-invasive, neuronal specific therapeutic strategy to adaptively control neuronal firing rates in the epileptic brain. o test the efficacy of this new technology, we will use the kainate acid model of experimental epilepsy in rats that has been demonstrated to produce an epilepsy syndrome similar to human temporal lobe epilepsy. At the end of the funding period we anticipate the development of a novel technology that could revolutionize therapeutic strategies of epilepsy management as well as introduce a new neuroscientific tool for studying the activity of neuronal networks associated with normal brain functions, other brain disorders and neuroplasticity.

描述（由申请人提供）：大约 35% 的癫痫患者对抗癫痫药物没有反应。其中，只有四分之一可以通过切除手术治疗。患有口语皮质癫痫发作、多灶性、双侧或全身性癫痫发作的患者不适合进行切除手术。对于这些患者，目前可用的一种治疗方法是通过电极进行神经刺激。神经刺激通过操纵远程控制系统或干扰致痫区本身来降低癫痫发作和传播的可能性。最近的证据表明，人类的癫痫发作可以通过适应性（闭环）即癫痫发作触发的刺激得到更好的控制。这需要 一种复杂的设置，集成了植入的刺激设备和实时分析技术。事实上，最近的研究表明，对患者进行闭环刺激可以有效降低癫痫发作频率和严重程度。然而，这种侵入性方法需要植入依赖于外部电源的复杂、大型和扩展的电子设备，需要进行重大且有时重复的脑部手术，以及神经刺激电极的实际放置经常产生意想不到的和不良的副作用。 我们的目标是开发一种替代性的、微创的、神经元特异性的治疗策略，以适应性地控制癫痫大脑中的神经元放电率。 为了测试这项新技术的功效，我们将使用大鼠实验性癫痫的红藻氨酸模型，该模型已被证明可以产生类似于人类颞叶癫痫的癫痫综合征。在资助期结束时，我们预计将开发出一种新技术，该技术可以彻底改变癫痫管理的治疗策略，并引入一种新的神经科学工具来研究与正常大脑功能、其他大脑疾病和神经可塑性相关的神经网络活动。