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: 8333669
• 负责人: Assaf A Gilad
• 金额: $ 32.33万
• 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/8333669
• 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）：约35％的癫痫患者对抗癫痫药不反应。其中，只有四分之一可以通过改良手术来治疗。由雄辩的皮质或多焦点，双边或广义的癫痫发作的患者不是候选手术的候选者。对于这些患者，目前可用的治疗是通过电极神经刺激。神经刺激通过操纵遥控系统或干扰癫痫发作区本身来降低癫痫发作的可能性和传播的可能性。最近的证据表明，可以通过适应性（闭环）更好地控制人类中的癫痫发作，即癫痫发作触发的刺激。这需要 一种集成植入刺激装置以及实时分析技术的复杂设置。实际上，最近的研究表明，患者的闭环刺激有效降低了癫痫发作的频率和严重程度。但是，这种侵入性方法遭受了需要植入复杂，大型和膨胀的电子设备，这些设备取决于外部电源，需要进行重复的，有时是重复性的脑手术以及出乎意料的和不良的副作用，而神经刺激电极的实际放置通常会产生。 我们旨在制定一种替代性，微创的，神经元特定的治疗策略，以适应性地控制癫痫大脑中的神经元发射率。 o测试这项新技术的功效，我们将使用大鼠的实验性癫痫的海藻酸模型，该模型已被证明会产生类似于人类颞叶癫痫类似的癫痫综合征。在资金期结束时，我们预计开发了一种新型技术，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，用于研究与正常脑功能，其他脑部障碍，其他脑部障碍和神经肿瘤性相关的神经元网络的活性。