Post-traumatic epilepsy (PTE) is acquired epilepsy after traumatic brain injury (TBI). Despite the availability of more than 20 antiseizure medications (ASMs), there is no way at present to prevent epileptogenesis in TBI survivors, and many cases of PTE become drug-resistant. Importantly, the adverse effects of ASMs can significantly affect patients' quality of life. Mammalian models are commonly used for studying refractory PTE, but are expensive and laborious. Zebrafish models have become popular for studying epilepsy, but most focus on larvae, and there have been no reports to date of pharmacological screening in an adult zebrafish model of acquired epilepsy. Valid animal models are critical for understanding PTE and for developing novel therapeutics. The aim of the present study was to characterize the cognitive impairments of a zebrafish model of TBI that leads to the development of PTE. Using combined behavioral and electrophysiological approaches, we also characterized the pharmacological effects of the most commonly used ASMs to manage PTE (valproate, carbamazepine, and phenytoin). Zebrafish with PTE exhibited impairments in learning and memory, difficulty in decision making, and reduced social preference. Valproate and carbamazepine had a limited protective effect against behavioral seizures, and all three drugs failed to significantly reduce electrographical seizures. The negative impacts of TBI and ASMs in zebrafish parallel those observed in other animals, making the zebrafish model of PTE a promising high-throughput model of refractory and drug-resistant epilepsy.

中文翻译：

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斑马鱼的创伤后癫痫具有耐药性并损害认知功能

创伤后癫痫（PTE）是创伤性脑损伤（TBI）后的获得性癫痫。尽管有超过 20 种抗癫痫药物 (ASM) 可用，但目前还没有办法预防 TBI 幸存者的癫痫发生，并且许多 PTE 病例变得耐药。重要的是，ASM 的不良反应会显着影响患者的生活质量。哺乳动物模型通常用于研究难治性 PTE，但价格昂贵且费力。斑马鱼模型已成为研究癫痫症的流行模型，但大多数集中在幼虫身上，迄今为止还没有关于成年斑马鱼获得性癫痫模型的药理学筛查的报道。有效的动物模型对于理解 PTE 和开发新疗法至关重要。本研究的目的是描述导致 PTE 发展的 TBI 斑马鱼模型的认知障碍。使用组合的行为和电生理方法，我们还描述了最常用的 ASM 管理 PTE（丙戊酸盐、卡马西平和苯妥英）的药理作用。患有 PTE 的斑马鱼表现出学习和记忆障碍、决策困难和社会偏好降低。丙戊酸盐和卡马西平对行为性癫痫发作的保护作用有限，三种药物均未能显着减少电图癫痫发作。TBI 和 ASMs 在斑马鱼中的负面影响与在其他动物中观察到的相似，使 PTE 的斑马鱼模型成为一种有前途的难治性和耐药性癫痫的高通量模型。