Noninvasive Seizure Screening in Preclinical Models of Epilepsy

癫痫临床前模型的无创性癫痫筛查 迫切需要研究癫痫和其他癫痫发作障碍的治疗方案。动物 模型越来越多地被用于了解疾病机制和筛选有前景的治疗方法 接近了。动物癫痫模型的使用通常需要昂贵和劳动密集型的实验， 有创性脑电测量是验证的首选方法。这严重限制了 调查。在获得性癫痫模型中，动物通常接受治疗以诱导癫痫持续状态- 无休止的癫痫发作--之后是一段潜伏期，在此期间大脑重新连接自身以产生 自发性癫痫发作，慢性癫痫的证据。潜伏期的持续时间和 动物罹患癫痫的可能性都是不确定的。动物必须观察数周才能 在他们准备好进行实验之前，先确认癫痫。在这一潜伏期内，癫痫发作通常 通过目视观察或视频审查来记录，这些方法繁琐且容易出错。一个商业体系 因此，自动化的非侵入性癫痫检测将吸引癫痫研究人员。 Signal Solutions，LLC已开发出基于压电式传感器的技术，用于非侵入性、高效率、 对啮齿动物的吞吐行为监测，目前由世界各地的研究小组用于 识别与睡眠和昼夜节律相关的基因。该系统通过以下方式区分睡眠和清醒 准确率超过90%。肯塔基大学的桑德兰实验室进一步展示了使用脑电 分析表明，这些压电传感器可以用来标记小鼠睡眠的REM和NREM阶段。 在这份STTR提案中，Pi Sunderam和合作调查员Bauer将与Signal Solutions合作开发 方法基于压电技术的鼠类模型无创性惊厥精确筛查 癫痫。其结果将是一个经过验证的系统，它将最大限度地减少对侵入性和资源密集型脑电的需求 分析或繁琐的视频监控。该项目的目标如下：1.测试项目的可行性 使用非侵入性压电传感器粗略检测啮齿类动物癫痫发作；2.训练压电分类器以 准确检测和量化确诊为癫痫的啮齿类动物的癫痫发作；以及3.测试微型仪器的实用性 用于癫痫筛查的压电传感器和用于癫痫验证和严重程度评估的红外成像仪。 设想的产品是一种交钥匙系统，用于对小动物进行方便和非侵入性的癫痫筛查 定制或商业笼子中的癫痫模型。潜在客户还包括学术研究实验室。 因为制药部门的实验室从事大量抗癫痫药物的筛选。

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.