Santana-Gómez César Emmanuel, Orozco-Suárez Sandra Adela, Talevi Alan, Bruno-Blanch Luis, Magdaleno-Madrigal Víctor Manuel, Fernández-Mas Rodrigo, Rocha Luisa
Department of Pharmacobiology, Center for Research and Advanced Studies (CINVESTAV), Mexico City, Mexico.
Unit for Medical Research in Neurological Diseases, Specialties Hospital, National Medical Center SXXI (CMN-SXXI), Mexico City, Mexico.
Neurotoxicology. 2017 Mar;59:110-120. doi: 10.1016/j.neuro.2017.01.009. Epub 2017 Feb 4.
Propylparaben (PPB) induces cardioprotection after ischemia-reperfusion injury by inhibiting voltage-dependent Na channels. The present study focuses on investigating whether the i.p. application of 178mg/kg PPB after pilocarpine-induced status epilepticus (SE) reduces the acute and long-term consequences of seizure activity. Initially, we investigated the effects of a single administration of PPB after SE. Our results revealed that compared to rats receiving diazepam (DZP) plus vehicle after 2h of SE, animals receiving a single dose of PPB 1h after DZP injection presented 126% (p<0.001) lower extracellular levels of glutamate in the hippocampus. This effect was associated with an increased potency of low-frequency oscillations (0.1-13Hz bands, p<0.001), a reduced potency of 30-250Hz bands (p<0.001) and less neuronal damage in the hippocampus. The second experiment examined whether the subchronic administration of PPB during the post-SE period is able to prevent the long-term consequences of seizure activity. In comparison to animals that were treated subchronically with vehicle after SE, rats administered with PPB for 5 days presented lower hippocampal excitability and interictal glutamate release, astrogliosis, and neuroprotection in the dentate gyrus. Our data indicate that PPB, when applied after SE, can be used as a therapeutic strategy to reduce the consequences of seizure activity.
对羟基苯甲酸丙酯(PPB)通过抑制电压依赖性钠通道在缺血再灌注损伤后诱导心脏保护作用。本研究着重调查在匹鲁卡品诱导的癫痫持续状态(SE)后腹腔注射178mg/kg的PPB是否能减轻癫痫活动的急性和长期后果。最初,我们研究了SE后单次给予PPB的效果。我们的结果显示,与在SE 2小时后接受地西泮(DZP)加赋形剂的大鼠相比,在DZP注射1小时后接受单次剂量PPB的动物海马中谷氨酸的细胞外水平降低了126%(p<0.001)。这种效应与低频振荡(0.1-13Hz频段,p<0.001)的增强、30-250Hz频段的减弱(p<0.001)以及海马中神经元损伤的减少有关。第二个实验研究了在SE后时期亚慢性给予PPB是否能够预防癫痫活动的长期后果。与SE后用赋形剂进行亚慢性治疗的动物相比,给予PPB 5天的大鼠海马兴奋性降低,发作间期谷氨酸释放减少,齿状回星形胶质细胞增生减少,具有神经保护作用。我们的数据表明,在SE后应用PPB可作为一种治疗策略来减轻癫痫活动的后果。