Traumatic brain injury (TBI) is a leading cause of death and disability in young adults worldwide. TBI survival is associated with persistent neuropsychiatric and neurological impairments, including posttraumatic epilepsy (PTE). To date, no pharmaceutical treatment has been found to prevent PTE or ameliorate neurological/neuropsychiatric deficits after TBI. Brain trauma results in immediate mechanical damage to brain cells and blood vessels that may never be fully restored given the limited regenerative capacity of brain tissue. This primary insult unleashes cascades of events, prominently including neuroinflammation and massive oxidative stress that evolve over time, expanding the brain injury, but also clearing cellular debris and establishing homeostasis in the region of damage. Accumulating evidence suggests that oxidative stress and neuroinflammatory sequelae of TBI contribute to posttraumatic epileptogenesis. This review will focus on possible roles of reactive oxygen species (ROS), their interactions with neuroinflammation in posttraumatic epileptogenesis, and emerging therapeutic strategies after TBI. We propose that inhibitors of the professional ROS-generating enzymes, the NADPH oxygenases and myeloperoxidase alone, or combined with selective inhibition of cyclooxygenase mediated signaling may have promise for the treatment or prevention of PTE and other sequelae of TBI.

This article is part of the special issue entitled ‘New Epilepsy Therapies for the 21st Century – From Antiseizure Drugs to Prevention, Modification and Cure of Epilepsy’.

创伤性脑损伤 (TBI) 是全世界年轻人死亡和残疾的主要原因。TBI 存活与持续的神经精神和神经功能障碍有关，包括创伤后癫痫 (PTE)。迄今为止，尚未发现药物治疗可以预防 PTE 或改善 TBI 后的神经/神经精神缺陷。脑外伤会立即对脑细胞和血管造成机械损伤，鉴于脑组织的再生能力有限，这种损伤可能永远无法完全恢复。这种主要的损伤会引发一系列事件，主要包括随着时间的推移而发生的神经炎症和大量氧化应激，扩大脑损伤，但也会清除细胞碎片并在损伤区域建立稳态。越来越多的证据表明，氧化应激和 TBI 的神经炎症后遗症会导致创伤后癫痫的发生。本综述将重点关注活性氧 (ROS) 的可能作用、它们与创伤后癫痫发生中神经炎症的相互作用，以及 TBI 后新兴的治疗策略。我们认为，专业ROS生成酶、NADPH加氧酶和髓过氧化物酶的抑制剂单独使用，或与环氧合酶介导的信号传导的选择性抑制相结合，可能有望治疗或预防 PTE 和 TBI 的其他后遗症。

本文是题为“21 世纪癫痫新疗法——从抗癫痫药物到癫痫的预防、改变和治愈”特刊的一部分。