Eslami Faezeh, Djedovic Arden, Loeb Jeffrey A
Department of Neurology and Rehabilitation, University of Illinois Chicago, 912 S Wood Street, 174N NPI M/C 796, Chicago, IL 60612, USA.
Brain Sci. 2024 Jun 25;14(7):634. doi: 10.3390/brainsci14070634.
Focal forms of epilepsy can result from a wide range of insults and can vary from focal symptoms to generalized convulsions. Most drugs that have been developed for epilepsy focus on the prevention of seizures. On Electroencephalography (EEG), seizures are characterized by a repetitive buildup of epileptic waveforms that can spread across the brain. Brain regions that produce seizures generate far more frequent 'interictal' spikes seen between seizures, and in animal models, these spikes occur prior to the development of seizures. Interictal spiking by itself has been shown to have significant adverse clinical effects on cognition and behavior in both patients and animal models. While the exact relationships between interictal spiking and seizures are not well defined, interictal spikes serve as an important biomarker that, for some forms of epilepsy, can serve as a surrogate biomarker and as a druggable target. While there are many animal models of seizures for drug development, here we review models of interictal spiking, focusing on tetanus toxin, to study the relationship between interictal spiking, seizures, cognition, and behavior. Studies on human cortical regions with frequent interictal spiking have identified potential therapeutic targets; therefore, having a highly consistent model of spiking will be invaluable not only for unraveling the initial stages of the pathological cascade leading to seizure development but also for testing novel therapeutics. This review offers a succinct overview of the use of tetanus toxin animal models for studying and therapeutic development for interictal spiking.
局灶性癫痫可由多种损伤引起，症状可从局灶性症状到全身性惊厥不等。大多数已开发的抗癫痫药物都侧重于预防癫痫发作。在脑电图（EEG）上，癫痫发作的特征是癫痫波形的重复增强，可在大脑中传播。产生癫痫发作的脑区在发作间期会产生更为频繁的“发作间期”尖峰，在动物模型中，这些尖峰在癫痫发作发展之前就会出现。在患者和动物模型中，发作间期尖峰本身已被证明会对认知和行为产生重大不良临床影响。虽然发作间期尖峰与癫痫发作的确切关系尚未明确，但发作间期尖峰是一种重要的生物标志物，对于某些形式的癫痫，它可以作为替代生物标志物和可药物治疗靶点。虽然有许多用于药物开发的癫痫发作动物模型，但在这里我们回顾发作间期尖峰模型，重点是破伤风毒素，以研究发作间期尖峰、癫痫发作、认知和行为之间的关系。对发作间期尖峰频繁的人类皮质区域的研究已经确定了潜在的治疗靶点；因此，拥有一个高度一致的尖峰模型不仅对于揭示导致癫痫发作发展的病理级联反应的初始阶段具有重要价值，而且对于测试新型治疗方法也具有重要价值。本综述简要概述了破伤风毒素动物模型在发作间期尖峰研究和治疗开发中的应用。
