Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University Health Science Center, Bryan, Texas.
Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University Health Science Center, Bryan, Texas
Pharmacol Rev. 2022 Apr;74(2):387-438. doi: 10.1124/pharmrev.121.000375.
Post-traumatic epilepsy (PTE) is one of the most devastating long-term, network consequences of traumatic brain injury (TBI). There is currently no approved treatment that can prevent onset of spontaneous seizures associated with brain injury, and many cases of PTE are refractory to antiseizure medications. Post-traumatic epileptogenesis is an enduring process by which a normal brain exhibits hypersynchronous excitability after a head injury incident. Understanding the neural networks and molecular pathologies involved in epileptogenesis are key to preventing its development or modifying disease progression. In this article, we describe a critical appraisal of the current state of PTE research with an emphasis on experimental models, molecular mechanisms of post-traumatic epileptogenesis, potential biomarkers, and the burden of PTE-associated comorbidities. The goal of epilepsy research is to identify new therapeutic strategies that can prevent PTE development or interrupt the epileptogenic process and relieve associated neuropsychiatric comorbidities. Therefore, we also describe current preclinical and clinical data on the treatment of PTE sequelae. Differences in injury patterns, latency period, and biomarkers are outlined in the context of animal model validation, pathophysiology, seizure frequency, and behavior. Improving TBI recovery and preventing seizure onset are complex and challenging tasks; however, much progress has been made within this decade demonstrating disease modifying, anti-inflammatory, and neuroprotective strategies, suggesting this goal is pragmatic. Our understanding of PTE is continuously evolving, and improved preclinical models allow for accelerated testing of critically needed novel therapeutic interventions in military and civilian persons at high risk for PTE and its devastating comorbidities. SIGNIFICANCE STATEMENT: Post-traumatic epilepsy is a chronic seizure condition after brain injury. With few models and limited understanding of the underlying progression of epileptogenesis, progress is extremely slow to find a preventative treatment for PTE. This study reviews the current state of modeling, pathology, biomarkers, and potential interventions for PTE and comorbidities. There's new optimism in finding a drug therapy for preventing PTE in people at risk, such as after traumatic brain injury, concussion, and serious brain injuries, especially in military persons.
创伤性脑损伤（TBI）后的癫痫（PTE）是最具破坏性的长期网络后果之一。目前尚无批准的治疗方法可以预防与脑损伤相关的自发性发作，许多 PTE 病例对抗癫痫药物耐药。创伤后癫痫发生是一种持久的过程，即正常大脑在头部受伤后表现出过度同步的兴奋性。了解癫痫发生中的神经网络和分子病理学是预防其发展或改变疾病进程的关键。在本文中，我们描述了对 PTE 研究现状的批判性评估，重点是实验模型、创伤后癫痫发生的分子机制、潜在的生物标志物以及 PTE 相关合并症的负担。癫痫研究的目标是确定新的治疗策略，以预防 PTE 的发生或中断致痫过程并缓解相关的神经精神合并症。因此，我们还描述了目前关于 PTE 后遗症治疗的临床前和临床数据。在动物模型验证、发病机制、癫痫发作频率和行为方面，我们概述了损伤模式、潜伏期和生物标志物的差异。改善 TBI 恢复和预防发作是复杂而具有挑战性的任务；然而，在这十年内，已经取得了很大的进展，证明了疾病修饰、抗炎和神经保护策略，表明这一目标是务实的。我们对 PTE 的理解在不断发展，改进的临床前模型允许加速测试对 PTE 及其破坏性合并症高危人群具有重要意义的新型治疗干预措施。意义：创伤后癫痫是脑损伤后的慢性癫痫发作。由于模型有限，对癫痫发生的潜在进展了解甚少，因此寻找预防 PTE 的治疗方法进展非常缓慢。本研究综述了 PTE 及其合并症的建模、病理学、生物标志物和潜在干预措施的现状。在高危人群中寻找预防 PTE 的药物治疗方法（如创伤性脑损伤、脑震荡和严重脑损伤后），例如在军事人员中，有了新的乐观情绪。
