Noninvasive Seizure Screening in Preclinical Models of Epilepsy

癫痫临床前模型中的无创性癫痫筛查

• 批准号: 9557948
• 负责人: Sridhar Sunderam
• 金额: $ 22.75万
• 依托单位: SIGNAL SOLUTIONS, LLC
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-15 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9557948
• 关键词: Aftercare; Algorithms; Alzheimer' s Disease; Animal Experimentation; Animal Model; Animals; Antiepileptic Agents; Behavior; Behavior monitoring; Behavioral; Brain; Cataplexy; Chronic; Circadian Rhythms; Communities; Computer software; Convulsants; Custom; Detection; Development; Devices; Disease; Drug Screening; Electroencephalography; Environment; Epilepsy; Epileptogenesis; Evaluation; Floor; Frontal Lobe Epilepsy; Funding; Genes; Genetic Models; Government; Image; Implanted Electrodes; Industrialization; Investigation; Kentucky; Knock-out; Label; Laboratory Animals; Lafora Disease; Measurement; Measures; Methods; Modeling; Monitor; Mus; Narcolepsy; Operative Surgical Procedures; Outcome; Persons; Pharmacologic Substance; Phase; Post-Traumatic Epilepsy; Pre-Clinical Model; Research; Research Personnel; Resources; Rodent; Rodent Model; Seizures; Severities; Signal Transduction; Sleep; Sleep Stages; Small Business Technology Transfer Research; Status Epilepticus; System; Technology; Temporal Lobe Epilepsy; Testing; Therapeutic; Time; Training; United States National Institutes of Health; Universities; Validation; Video Recording; Visual; Wakefulness; Work; base; commercialization; dravet syndrome; imager; implantation; interest; natural hypothermia; neonatal stroke; new technology; perinatal stroke; pressure; respiratory; screening; sensor; therapy development; trait; treatment effect; voltage

Noninvasive Seizure Screening in Preclinical Models of Epilepsy There is an urgent need for research into treatment options for epilepsy and other seizure disorders. Animal models are increasingly used to understand disease mechanisms and to screen promising therapeutic approaches. Animal epilepsy model use typically requires expensive and labor-intensive experimentation, with invasive EEG measurements being the preferred method of validation. This severely limits the pace and scale of investigation. In models of acquired epilepsy, animals usually undergo treatment to induce status epilepticus— a period of unremitting seizure—followed by a latent period during which the brain rewires itself to generate spontaneously recurring seizures, evidence of chronic epilepsy. The duration of the latent period and the likelihood that an animal will develop epilepsy are both uncertain. Animals must be observed for weeks to confirm epilepsy before they are ready for experimentation. During this latent period, seizures are commonly documented by visual observation or video review, which are tedious and prone to error. A commercial system for automated noninvasive seizure detection would therefore be attractive to epilepsy researchers. Signal Solutions, LLC, has developed technology based on piezoelectric sensors for noninvasive, high- throughput behavioral monitoring of rodents that is currently used by research groups around the world to identify genes related to sleep and circadian rhythms. The system discriminates sleep from wakefulness with over 90% accuracy. The Sunderam Lab at the University of Kentucky has further demonstrated using EEG analysis that these piezo sensors can be used to label REM and NREM stages of sleep in mice. In this STTR proposal, PI Sunderam and co-investigator Bauer will work with Signal Solutions to develop methods based on the piezo technology for accurate noninvasive seizure screening in rodent models of epilepsy. The result will be a validated system that minimizes the need for invasive and resource-intensive EEG analysis or tedious video monitoring. The objectives of the project are the following: 1. Test the feasibility of coarse detection of epilepsy onset in rodents using a noninvasive piezo sensor; 2. Train a piezo classifier to accurately detect and quantify seizures in rodents with confirmed epilepsy; and 3. Test the utility of a miniature piezo sensor for seizure screening and an infrared imager for seizure verification and severity assessment. The envisioned product is a turnkey system for convenient and noninvasive seizure screening in small animal models of epilepsy in custom or commercial cages. Potential customers include academic research labs as well as labs in the pharmaceutical sector engaged in high-volume screening of antiepileptic drugs.

癫痫的临床前模型中的无创癫痫发作筛查 迫切需要研究癫痫和其他癫痫病的治疗选择。动物 模型越来越多地用于理解疾病机制并筛查有希望的治疗 方法。动物癫痫模型的使用通常需要昂贵且劳动密集型的实验，并需要 侵入性脑电图测量是首选的验证方法。这严重限制了 投资。在获得癫痫的模型中，动物通常接受治疗以诱导癫痫持续状态 - 一个不易癫痫发作的时期 - 由一个潜在时期遵循，在此期间，大脑会重新布线产生 赞成癫痫发作，慢性癫痫的证据。潜在时期和 动物发育癫痫的可能性都是不确定的。必须观察动物数周 在准备实验之前确认发作。在这个潜在时期，癫痫发作通常是 通过视觉观察或视频审查记录，这些审查乏味且容易出错。商业系统 因此，对于自动化的非侵入性癫痫发作检测将对癫痫研究人员有吸引力。 Signal Solutions，LLC已开发了基于压电传感器的技术，用于非侵入性，高级 全球研究小组目前使用的啮齿动物的吞吐量行为监测 识别与睡眠和昼夜节律有关的基因。该系统将睡眠与清醒区分开 超过90％的精度。肯塔基大学的Sunderam实验室已进一步证明 分析这些压电传感器可用于标记小鼠睡眠的REM和NREM阶段。 在此STTR提案中，Pi Sunderam和共同研究器Bauer将使用信号解决方案来开发 基于压电技术的方法，用于精确的无创癫痫发作筛查 癫痫。结果将是一个经过验证的系统，可最大程度地减少对侵入性和资源密集型脑电图的需求 分析或乏味的视频监控。项目的目标如下：1。测试可行性 使用非侵入性压电传感器对啮齿动物中癫痫发作的粗略检测； 2。训练压电分类器 准确检测并量化确认癫痫的啮齿动物的癫痫发作；和3。测试微型的实用程序 用于癫痫发作的压电传感器和用于癫痫发作验证和严重性评估的红外成像仪。 设想的产品是一个交钥匙系统，用于在小动物中方便且无创癫痫发作筛查 定制或商业笼子中的癫痫模型。潜在客户也包括学术研究实验室 作为药物领域的实验室，从事抗癫痫药的大规模筛查。