Department of Pharmacology, University of Arizona College of Medicine, 1501 N. Campbell Avenue, Tucson, AZ 85724-5050, USA.
Neuropharmacology. 2013 Jun;69:3-15. doi: 10.1016/j.neuropharm.2012.01.022. Epub 2012 Feb 4.
The "latent period" between brain injury and clinical epilepsy is widely regarded to be a seizure-free, pre-epileptic state during which a time-consuming cascade of molecular events and structural changes gradually mediates the process of "epileptogenesis." The concept of the "latent period" as the duration of "epileptogenesis" implies that epilepsy is not an immediate result of brain injury, and that anti-epileptogenic strategies need to target delayed secondary mechanisms that develop sometime after an initial injury. However, depth recordings made directly from the dentate granule cell layers in awake rats after convulsive status epilepticus-induced injury have now shown that whenever perforant pathway stimulation-induced status epilepticus produces extensive hilar neuron loss and entorhinal cortical injury, hyperexcitable granule cells immediately generate spontaneous epileptiform discharges and focal or generalized behavioral seizures. This indicates that hippocampal injury caused by convulsive status epilepticus is immediately epileptogenic and that hippocampal epileptogenesis requires no delayed secondary mechanism. When latent periods do exist after injury, we hypothesize that less extensive cell loss causes an extended period during which initially subclinical focal seizures gradually increase in duration to produce the first clinical seizure. Thus, the "latent period" is suggested to be a state of "epileptic maturation," rather than a prolonged period of "epileptogenesis," and therefore the antiepileptogenic therapeutic window may only remain open during the first week after injury, when some delayed cell death may still be preventable. Following the perhaps unavoidable development of the first focal seizures ("epileptogenesis"), the most fruitful therapeutic strategy may be to interrupt the process of "epileptic maturation," thereby keeping focal seizures focal. This article is part of the Special Issue entitled 'New Targets and Approaches to the Treatment of Epilepsy'.
“潜伏期”是指脑损伤与临床癫痫之间的无癫痫发作、癫痫前期状态，在此期间，分子事件和结构变化的级联反应会逐渐介导“癫痫发生”过程。“潜伏期”作为“癫痫发生”持续时间的概念表明，癫痫不是脑损伤的直接结果，抗癫痫发生策略需要针对初始损伤后一段时间才发展的延迟性二级机制。然而，直接在清醒大鼠的齿状回颗粒细胞层进行深度记录，发现惊厥性癫痫持续状态诱导损伤后，只要穿通纤维通路刺激诱导的癫痫持续状态导致广泛的颗粒细胞层神经元丢失和内嗅皮质损伤，兴奋性过高的颗粒细胞就会立即产生自发性癫痫样放电和局灶性或全身性行为性癫痫发作。这表明，惊厥性癫痫持续状态引起的海马损伤立即具有致癫痫性，海马癫痫发生不需要延迟的二级机制。当损伤后确实存在潜伏期时，我们假设较轻的细胞丢失会导致一个延长的时期，在此期间，最初的亚临床局灶性癫痫逐渐延长，从而导致首次临床癫痫发作。因此，“潜伏期”被认为是一种“癫痫成熟”状态，而不是“癫痫发生”的延长时期，因此抗癫痫发生的治疗窗口可能仅在损伤后第一周内保持开放，此时一些延迟性细胞死亡可能仍然可以预防。在首次局灶性癫痫发作（“癫痫发生”）的发展之后，最有效的治疗策略可能是中断“癫痫成熟”过程，从而使局灶性癫痫保持局灶性。本文是特刊“癫痫治疗的新靶点和新方法”的一部分。
