Pediatric Department of Qilu Hospital, Shandong University, Jinan, China.
Med Hypotheses. 2011 Feb;76(2):184-6. doi: 10.1016/j.mehy.2010.09.013.
Epileptogenesis is defined as the process of developing epilepsy - a disorder characterized by recurrent seizures - following an initial insult. Neuronal death, aberrant synaptic plasticity and neuroinflammation play essential roles in epileptogenesis. An effective neuroprotective therapeutic agent should counteract one or, ideally, all the above-mentioned mechanisms. However, antiepileptic drugs obtainable nowadays can only suppress seizures, without antiepileptogenic effects. Matrix metalloproteinase-9 (MMP-9) is a member of matrix metalloproteinase (MMP) family that remodels the extracellular matrix. Recently, cumulative evidence indicates that MMP-9, a key participant in neuronal death, aberrant synaptic plasticity and neuroinflammation, is upregulated in experimental epilepsy models. Increased MMP-9 is also implicated in clinical epilepsy studies. Thus, we hypothesize that MMP-9 may be a novel therapeutic target for epilepsy and some agents, such as S24994, atorvastatin and minocycline, may be potential antiepileptogenic drugs.
癫痫发生定义为在初始损伤后发展为癫痫 - 一种以反复发作为特征的疾病。神经元死亡、异常的突触可塑性和神经炎症在癫痫发生中起重要作用。有效的神经保护治疗剂应该对抗一种或理想情况下所有上述机制。然而,目前可获得的抗癫痫药物只能抑制发作,而没有抗癫痫发生的作用。基质金属蛋白酶-9(MMP-9)是基质金属蛋白酶(MMP)家族的一员,可重塑细胞外基质。最近,越来越多的证据表明,MMP-9 是神经元死亡、异常的突触可塑性和神经炎症的关键参与者,在实验性癫痫模型中上调。MMP-9 的增加也与临床癫痫研究有关。因此,我们假设 MMP-9 可能是癫痫的一个新的治疗靶点,一些药物,如 S24994、阿托伐他汀和米诺环素,可能是潜在的抗癫痫药物。