Velísek Libor, Velísková Jana
The Saul R. Korey of Department of Neurology, Einstein/Montefiore Comprehensive Epilepsy Management Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Recent Pat CNS Drug Discov. 2008 Jun;3(2):128-37. doi: 10.2174/157488908784534577.
Current epilepsy therapy is symptomatic using antiepileptic drugs. This therapy suppresses seizures but does not prevent or cure epilepsy. Treatment strategies that could interfere with the process leading to epilepsy (epileptogenesis) would have significant benefits over the current approach. Neuronal damage contributing to restructuralization of the neuronal networks (especially in the hippocampus during temporal lobe epilepsy) is one of the significant components of ongoing epileptogenesis. Thus, treatment strategies alleviating seizure induced neuronal damage may become significant players against the deteriorating process of epileptogenesis. Current antiepileptic drugs, especially valproic acid, have some neuroprotective potential. However, frequently this potential is either insufficient or the side effects of long-term therapy cancel out the benefits. The attention is therefore aimed at different classes of drugs with already established neuroprotective potential. Steroid hormones are under investigation, especially two groups of these compounds: beta-estradiol and the selective estrogen receptor modulators--SERM. In low doses, beta-estradiol has neuroprotective potency in neurodegenerative diseases. However, its use in seizure-induced neuroprotection is confounded by the common perception of proconvulsant features of estrogens. Here, we review that both proconvulsant and neuroprotective features apply only under specific conditions and may be separated by therapy taking into account the dosage paradigm, timing, sex of the subjects and their gonadal hormone status. Several studies have demonstrated that beta-estradiol has indeed potency to protect neurons from seizure-induced damage. Additional studies are required to further elucidate the effects, exact conditions, and especially mechanisms of action of beta-estradiol in seizure-induced neuroprotection since new specific SERM may help to avoid some undesirable effects.
目前的癫痫治疗采用抗癫痫药物，属于对症治疗。这种疗法可抑制癫痫发作，但无法预防或治愈癫痫。能够干扰导致癫痫（癫痫发生）过程的治疗策略将比当前方法具有显著优势。导致神经网络重构（尤其是颞叶癫痫时海马体中的神经网络重构）的神经元损伤是正在进行的癫痫发生的重要组成部分之一。因此，减轻癫痫发作引起的神经元损伤的治疗策略可能成为对抗癫痫发生恶化过程的重要手段。目前的抗癫痫药物，尤其是丙戊酸，具有一定的神经保护潜力。然而，这种潜力往往不足，或者长期治疗的副作用抵消了益处。因此，人们将注意力转向具有已确定神经保护潜力的不同类别药物。类固醇激素正在研究中，尤其是其中两组化合物：β-雌二醇和选择性雌激素受体调节剂（SERM）。低剂量时，β-雌二醇在神经退行性疾病中具有神经保护作用。然而，由于人们普遍认为雌激素具有促惊厥特性，其在癫痫发作诱导的神经保护中的应用受到了困扰。在此，我们回顾指出，促惊厥和神经保护特性仅在特定条件下适用，并且可以通过考虑剂量模式、时间、受试者性别及其性腺激素状态的治疗来区分。多项研究表明，β-雌二醇确实具有保护神经元免受癫痫发作诱导损伤的能力。由于新的特异性SERM可能有助于避免一些不良影响，因此需要进一步研究以阐明β-雌二醇在癫痫发作诱导的神经保护中的作用、确切条件，尤其是作用机制。
