Department of Pathophysiology, Medical University of Lublin, 20-090 Lublin, Poland.
Laboratory of Ischemic and Neurodegenerative Brain Research, Mossakowski Medical Research Centre, Polish Academy of Sciences, 02-106 Warsaw, Poland.
Int J Mol Sci. 2020 Mar 28;21(7):2340. doi: 10.3390/ijms21072340.
Generally, the prevalence of epilepsy does not exceed 0.9% of the population and approximately 70% of epilepsy patients may be adequately controlled with antiepileptic drugs (AEDs). Moreover, status epilepticus (SE) or even a single seizure may produce neurodegeneration within the brain and SE has been recognized as one of acute brain insults leading to acquired epilepsy via the process of epileptogenesis. Two questions thus arise: (1) Are AEDs able to inhibit SE-induced neurodegeneration? and (2) if so, can a probable neuroprotective potential of particular AEDs stop epileptogenesis? An affirmative answer to the second question would practically point to the preventive potential of a given neuroprotective AED following acute brain insults. The available experimental data indicate that diazepam (at low and high doses), gabapentin, pregabalin, topiramate and valproate exhibited potent or moderate neuroprotective effects in diverse models of SE in rats. However, only diazepam (at high doses), gabapentin and pregabalin exerted some protective activity against acquired epilepsy (spontaneous seizures). As regards valproate, its effects on spontaneous seizures were equivocal. With isobolography, some supra-additive combinations of AEDs have been delineated against experimental seizures. One of such combinations, levetiracetam + topiramate proved highly synergistic in two models of seizures and this particular combination significantly inhibited epileptogenesis in rats following status SE. Importantly, no neuroprotection was evident. It may be strikingly concluded that there is no correlation between neuroprotection and antiepileptogenesis. Probably, preclinically verified combinations of AEDs may be considered for an anti-epileptogenic therapy.
一般来说，癫痫的患病率不超过人口的 0.9%，大约 70%的癫痫患者可以通过抗癫痫药物（AEDs）得到充分控制。此外，癫痫持续状态（SE）甚至单次发作都可能导致大脑内的神经退行性变，SE 已被认为是导致获得性癫痫的急性脑损伤之一，通过癫痫发生的过程。因此，出现了两个问题：（1）AED 能否抑制 SE 诱导的神经退行性变？（2）如果可以，特定 AED 的可能神经保护潜能是否可以阻止癫痫发生？对第二个问题的肯定回答实际上将指向特定神经保护 AED 在急性脑损伤后的预防潜力。现有的实验数据表明，地西泮（低剂量和高剂量）、加巴喷丁、普瑞巴林、托吡酯和丙戊酸钠在大鼠 SE 的不同模型中表现出强大或中等的神经保护作用。然而，只有地西泮（高剂量）、加巴喷丁和普瑞巴林对获得性癫痫（自发性癫痫）表现出一些保护活性。至于丙戊酸钠，其对自发性癫痫的影响尚无定论。通过等辐射图，已经确定了一些 AED 的超加和组合对实验性癫痫发作具有治疗作用。其中一种组合，左乙拉西坦+托吡酯在两种癫痫发作模型中表现出高度协同作用，这种特定组合在 SE 后显著抑制了大鼠的癫痫发生。重要的是，没有明显的神经保护作用。可以得出结论，神经保护与抗癫痫发生之间没有相关性。也许，可以考虑在临床前验证的 AED 组合用于抗癫痫发生治疗。
