PENTİLENETETRAZOLE VE KAİNİK ASİT İLE OLUŞTURULAN STATUS EPİLEPTİKUS MODELLERİNDE ÖĞRENME VE DAVRANIŞ DEĞİŞİKLİKLERİ

Abstract

En az 30 dakika boyunca devam eden veya nöbetler arası bilincin tam olarak düzelmediği iki veya daha fazla tekrarlayan nöbetler Status Epileptikus (SE) olarak bilinir. Bu çalışmada iki farklı SE modeli oluşturularak, antiepileptik ilaçlardan biri olan Levetirasetam’ın epileptogenez süreci ve kognitif fonksiyonlar üzerine olan etkilerinin değerlendirilmesi amaçlanmıştır. Çalışma 87 adet, immatür (21 günlük) erkek Wistar sıçanlarla başlamış ancak nöbet sonrası ex olan hayvanlar çıkarıldığında toplam 74 sıçanla deneyler devam etmiştir. Bu sıçanlar altı gruba ayrılmıştır. Pentilentetrazol (PTZ) enjeksiyonu ile epilepsi modeli geliştirilecek gruplara on dakika ara ile 40 mg/kg, 20 mg/kg, 10 mg/kg dozlarda PTZ intraperitoneal olarak verilmiştir. Kainik asit (KA) ile oluşturulan nöbetlerde tek doz 10 mg/kg KA intraperitoneal olarak enjekte edilmiştir. Antiepileptik alacak gruplara nöbet gününden başlayarak 14 gün boyunca ip olarak 200 mg/kg dozunda Levetirasetam (Keppra) verildi. SE oluşumundan iki hafta sonra uzamsal öğrenme için Morris su tankı testi, emosyonel öğrenme için yükseltilmiş T labirent testi, davranış değişiklikleri için de açık alan düzeneği kullanılarak değerlendirmeler yapılmıştır. Ayrıca beyin dokusu çıkarılarak histopatolojik analizleri ve apoptotik durumları değerlendirilmiştir. Açık alan düzeneğinde geçtikleri kare sayısı bakımından gruplar arasında anlamlı bir fark bulunamamıştır. Yükseltilmiş T labirent testinde pasif sakınmada gruplar arasında istatistiksel olarak anlamlı bir fark bulunmuştur (p<0.05). Morris su tankı ile yapılan test sonuçlarına göre gruplar arasında anlamlı bir fark bulunamamıştır. Kortekste yapılan histolojik değerlendirmelerde SE geçiren gruplarda dejenerasyon gözlenmiştir. KA ve PTZ grupları karşılaştırıldığında KA ile oluşturulan SE modelindeki hasarın PTZ grubundan daha büyük olduğu gözlenmiştir. Sonuç olarak Levetirasetam, PTZ grubunda KA grubuna göre daha etkili olmuştur ve Levetirasetam tedavisi sonrası apoptoz, KA ve PTZ gruplarında azalmıştır.

Keywords

• İmmatür
• kainik asit
• öğrenme
• pentilentetrazol
• status epileptikus

LEARNING AND BEHAVIORAL CHANGES IN STATUS EPILEPTICUS MODELS INDUCED BY PENTYLENETETRAZOLE AND KAINIC ACID

Abstract

Status epilepticus (SE) is a recurrent, intermittent or continuous disease lasting 30 minutes without regaining consciousness. This study aims to evaluate the effects of Levetiracetam, one of the antiepileptic drugs, on epileptogenesis process and cognitive functions by creating two different status models. The study started with 87 twenty-one-day-old immature male Wistar rats, removing the ones dieing after the seizure, continued with 74 rats divided into six groups. Pentylenetetrazole (PTZ) was administered intraperitoneally at 40 mg/kg, 20 mg/kg, 10 mg/kg doses at ten minutes intervals to the groups in which the epilepsy model was to be developed by PTZ injection. In seizures induced by kainic acid (KA), a single dose of 10 mg/kg KA was injected intraperitoneally. Levetiracetam (Keppra) at a döşe of 200 mg/kg ip for 14 days starting from the day of seizure was administered to the antiepileptic groups. Two weeks after SE formation, assessments were made using Morris water tank test for spatial learning, elevated T maze test for emotional learning, and open field area for behavioral changes. Besides, brain tissue was removed and histopathologic analysis and apoptotic status were evaluated. There was no significant difference between the groups regarding the number of squares passed in the open field test. A statistically significant difference was found between the groups in passive avoidance in the elevated T maze test (p<0.05). according to the results of the test with Morris water tank, no significant difference was found between the groups. Histologic evaluations of the cortex showed degeneration in the SE groups. When KA and PTZ groups were compared, the damage in the SE model created with KA was found to be greater than that in the PTZ group. Levetiracetam was found to be more effective in the PTZ group than in the KA group. Apoptosis was observed to decrease in KA and PTZ groups after levetiracetam treatment.

Keywords

• Immature
• kainic acid
• learning
• pentylenetetrazole
• status epilepticus

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