Radzik Iwona, Miziak Barbara, Dudka Jarosław, Chrościńska-Krawczyk Magdalena, Czuczwar Stanisław J
Department of Pathophysiology, Medical University of Lublin, Lublin, Poland.
Department of Toxicology, Medical University of Lublin, Lublin, Poland; Independent Medical Biology Unit, Medical University of Lublin, Lublin, Poland.
Pharmacol Rep. 2015 Jun;67(3):663-8. doi: 10.1016/j.pharep.2015.01.016. Epub 2015 Feb 9.
Epilepsy is a common neurologic disease, affecting about 1-2% of the population. In around 30% of patients with epilepsy, their seizures are not satisfactorily controlled and drug-resistant epilepsy constitutes a real therapeutic challenge. Consequently, there are efforts aimed at the inhibition of epileptogenesis, a process of converting a normal into an epileptic brain. Data on this problem have been mainly obtained in post-status epilepticus rodent models in which spontaneous seizure activity and behavioral disturbances develop over time. Among antiepileptic drugs, diazepam at high dose of 20mg/kg given during status epilepticus, significantly inhibited the development of spontaneous seizures and also, a strong neuroprotective effect was evident. Also gabapentin and valproate (over a period of 40 days) proved effective in the inhibition of spontaneous seizure activity and reduction of behavioral deficit. However, there are also data that valproate (over 28 days) significantly improved the behavioral performance without affecting the occurrence of spontaneous seizures. A number of antiepileptic drugs, carbamazepine, lamotrigine, levetiracetam, phenobarbital, and topiramate were completely ineffective. Among non-antiepileptic drugs, some promise show rapamycin, losartan and combinations of anti-inflammatory drugs, targeting different inflammatory pathways. Inhibition of epileptogenesis may become a valuable therapeutic approach provided that there are reliable markers of this process. Actually, such markers begin to emerge.
癫痫是一种常见的神经系统疾病，影响着约1%至2%的人口。在大约30%的癫痫患者中，他们的癫痫发作未能得到令人满意的控制，耐药性癫痫构成了真正的治疗挑战。因此，人们致力于抑制癫痫发生，即把正常大脑转变为癫痫大脑的过程。关于这个问题的数据主要是在癫痫持续状态后的啮齿动物模型中获得的，在这些模型中，随着时间的推移会出现自发癫痫活动和行为障碍。在抗癫痫药物中，癫痫持续状态期间给予高剂量（20mg/kg）的地西泮可显著抑制自发癫痫发作的发展，并且还具有明显的强大神经保护作用。加巴喷丁和丙戊酸盐（在40天的时间段内）也被证明对抑制自发癫痫活动和减少行为缺陷有效。然而，也有数据表明丙戊酸盐（超过28天）可显著改善行为表现，而不影响自发癫痫发作的发生。一些抗癫痫药物，如卡马西平、拉莫三嗪、左乙拉西坦、苯巴比妥和托吡酯则完全无效。在非抗癫痫药物中，一些药物如雷帕霉素、氯沙坦以及针对不同炎症途径的抗炎药物组合显示出了一定前景。如果有该过程的可靠标志物，抑制癫痫发生可能会成为一种有价值的治疗方法。实际上，这样的标志物已开始出现。
