Ersin BEYAZCİCEK, Handan ANKARALİ, Serif DEMİR, Seyit ANKARALİ

The Effect of Rapamycin on Penicillin-Induced Epileptiform Activity in Rats: An Electrophysiological Study

Amaç: Yeryüzünde yaklaşık elli milyon insan epilepsinin pençesindedir ve bu hastaların büyük bir bölümü şimdiye kadar keşfedilmiş antiepileptik ilaçlara karşı dirençlidir. Bunun yanı sıra, bu ilaçların yan etki profilleri de oldukça geniştir. Memelideki rapamisin hedefi (mTOR) inhibitörü olan rapamisin; antineoplastik, yaşlanmayı geciktirici ve antienflamatuvar etkilere sahiptir. mTOR'un sinir sistemi üzerindeki etkilerine dair çalışmalarda ise nöroprotektif etkisinin olduğu gösterilmiştir. Buna ek olarak, tüberoskleroz hastalarında rapamisin kullanımının epileptik nöbetleri azalttığı bildirilmiştir. Bu çalışmanın amacı mTOR inhibitörü rapamisinin sıçanlarda penisilinle oluşturulmuş deneysel epilepsi üzerindeki akut etkisini araştırmaktır. Gereç ve Yöntemler: Bu çalışmada penisilinle oluşturulmuş deneysel epilepsili kırk adet erişkin erkek Wistar sıçan içeren bir model kullanılmıştır. Söz konusu kırk sıçan; salin, çözücü (dimetilsülfoksit), ve de 0,1 mg/kg, 0,4 mg/kg ve 0,8 mg/kg rapamisin grupları olmak üzere beş gruba ayrıldı. Tüm maddeler intraperitoneal yolla uygulandı. Sıçanlara anestezi için 1,25 g/kg üretan uygulandıktan sonra hayvanların sol kafatası açıldı ve beyin üzerine elektrotlar yerleştirildi. Elektrokortikografi kaydı başlatıldı. Rapamisin uygulamasından iki saat sonra intrakortikal olarak penisilin uygulandı. Penisilin uygulandıktan sonra elektrokortikografi verileri iki saat daha kaydedildi. Bulgular: Rapamisinle tedavi edilen sıçan gruplarında, 0,4 mg/kg ve 0,8 mg/kg rapamisin uygulamaları epileptiform aktivitenin diken-dalga sıklığını ve genliğini anlamlı olarak azaltmıştır. Fakat latensleri karşılaştırıldığında gruplar arasında anlamlı bir fark bulunmamıştır.Tartışma ve Sonuç: Akut rapamisin uygulaması sıçanlarda penisilinle oluşturulmuş epileptiform aktivitenin diken-dalga sıklığını ve diken-dalga genliğini azaltmıştır ve bu bulgular rapamisinin antiepileptojenik bir potansiyele sahip olduğunu göstermektedir

Rapamisinin Sıçanlarda Penisilinle Oluşturulmuş Epileptiform Aktivite Üzerine Etkisi: Bir Elektrofizyolojik Çalışma

Aim: Approximately fifty million people in the world suffer from epilepsy, and a large part of these patients are resistant to antiepileptic drugs discovered so far. In addition, side effect profiles of these drugs are very wide. Rapamycin that is an inhibitor of mammalian target of rapamycin (mTOR) has antineoplastic, aging-retarding, and anti-inflammatory effects. The studies regarding the effects of mTOR on nervous system have shown that it has neuro-protective effects. Moreover, it has been reported that use of rapamycin reduces epileptic seizures in tuberous sclerosis patients. In this study we aimed to investigate acute effects of the mTOR inhibitor rapamycin on penicillin-induced experimental epilepsy in rats.Materials and Methods: In this study, a model of forty adult male Wistar rats with penicillininduced experimental epilepsy was used. The forty rats were divided into five groups, which were saline group, solvent (dimethylsulfoxide) group, and 0.1 mg/kg, 0.4 mg/kg and 0.8 mg/kg rapamycin groups. All substances were administered intraperitoneally. After the administration of 1.25 g/kg urethane for anesthesia, the left part of each rat's skull was opened and electrodes were placed on the brain. Electrocorticography recording was initiated. Penicillin was intracortically administered two hours after the administration of rapamycin. After the administration of penicillin, electrocorticographic data were recorded for another two hours.Results: In rapamycin-treated rat groups, administration of 0.4 mg/kg and 0.8 mg/kg rapamycin significantly reduced epileptic spike-wave frequency and amplitude of epileptiform activity. However, when compared in terms of latency no significant difference was found between the groups.Discussion and Conclusion: Acute administration of rapamycin reduced spike-wave frequency and spike-wave amplitude of penicillin-induced epileptiform activity in the rats, and these findings indicate that rapamycin has an antiepileptogenic potential

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