Epilepsy Center, Department of Neurosurgery, University Hospital Freiburg, Breisacher Straße 64, 79106 Freiburg, Germany.
Biomed Res Int. 2013;2013:497485. doi: 10.1155/2013/497485. Epub 2013 Sep 14.
In neocortical epilepsies not satisfactorily responsive to systemic antiepileptic drug therapy, local application of antiepileptic agents onto the epileptic focus may enhance treatment efficacy and tolerability. We describe the effects of focally applied valproate (VPA) in a newly emerging rat model of neocortical epilepsy induced by tetanus toxin (TeT) plus cobalt chloride (CoCl₂).
In rats, VPA (n = 5) or sodium chloride (NaCl) (n = 5) containing polycaprolactone (PCL) implants were applied onto the right motor cortex treated before with a triple injection of 75 ng TeT plus 15 mg CoCl₂. Video-EEG monitoring was performed with intracortical depth electrodes.
All rats randomized to the NaCl group died within one week after surgery. In contrast, the rats treated with local VPA survived significantly longer (P < 0.01). In both groups, witnessed deaths occurred in the context of seizures. At least 3/4 of the rats surviving the first postoperative day developed neocortical epilepsy with recurrent spontaneous seizures.
The novel TeT/CoCl₂ approach targets at a new model of neocortical epilepsy in rats and allows the investigation of local epilepsy therapy strategies. In this vehicle-controlled study, local application of VPA significantly enhanced survival in rats, possibly by focal antiepileptic or antiepileptogenic mechanisms.
在全身性抗癫痫药物治疗效果不理想的新皮层癫痫中，将抗癫痫药物局部应用于癫痫灶可能会提高治疗效果和耐受性。我们描述了局部应用丙戊酸钠（VPA）在破伤风毒素（TeT）加氯化钴（CoCl₂）诱导的新出现的大鼠新皮层癫痫模型中的作用。
在大鼠中，将含有聚己内酯（PCL）的 VPA（n = 5）或氯化钠（NaCl）（n = 5）植入物应用于之前接受过 75ng TeT 加 15mg CoCl₂三重注射的右侧运动皮层。使用皮层内深部电极进行视频-脑电图监测。
所有随机分配到 NaCl 组的大鼠均在手术后一周内死亡。相比之下，接受局部 VPA 治疗的大鼠存活时间明显更长（P < 0.01）。在两组中，有目击记录的死亡都发生在癫痫发作的背景下。至少有 3/4 在术后第一天存活下来的大鼠发展为新皮层癫痫，伴有反复自发发作。
新的 TeT/CoCl₂方法针对大鼠的新皮层癫痫模型，并允许研究局部癫痫治疗策略。在这项对照研究中，局部应用 VPA 显著提高了大鼠的存活率，可能通过局部抗癫痫或抗癫痫发生机制。
