Rho/Rho-kinase (ROCK) signaling contributes to neuroinflammation, epileptogenesis, and seizures in convulsive-type epilepsies. However, this pathway has not been investigated in absence epilepsy. We investigated RhoA activity in genetic absence epilepsy rats from Strasburg (GAERS) and the effects of ROCK inhibitors Y-27632 and fasudil on spike-and-wave discharges (SWDs) of GAERS. ROCK level and activity were measured by Western blot analysis in the brain areas involved in absence seizures (i.e., cortex and thalamus) and hippocampus. Male GAERS were stereotaxically implanted with bilateral cortical electrodes for electroencephalogram (EEG) recordings and/or guide cannula into the right ventricle. ROCK inhibitors were administered by intraperitoneal injection (1-10 mg/kg for Y-27632 or fasudil) or intracerebroventricular injection (7-20 nmol/5 μl for Y-27632 or 10-100 nmol/5 μl for fasudil). EEG was recorded under freely moving conditions. Compared with Wistar rats, GAERS exhibited increased RhoA activity in the somatosensory cortex but not in the thalamus or hippocampus. The single systemic administration of Y-27632 and fasudil partially suppressed the duration and frequency of absence seizure, respectively. However, local brain administration caused a widespread suppressive effect on the total seizure duration, number of seizures, and the average individual seizure length. In summary, Rho/ROCK signaling may be involved in the pathophysiology of absence epilepsy. Furthermore, ROCK inhibitors can control the expression of absence seizure in GAERS, thus indicating that Y-27632 and fasudil have the potential to be used as novel anti-absence drugs.

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Toxic honey, containing grayanotoxin, is obtained from nectar and polen of rhododendron. Consumed in excess it produces seizures and convulsions. In order to investigate whether the toxic honey extract can be used as a seizure model, we examined the electroencephalographic (EEG) and motor effects of intracerebroventricular (icv) or intraperitoneal (ip) injection of toxic honey extract in Wistar rats or in genetic absence epilepsy rats from Strasbourg (GAERS). Male Wistar rats or GAERS were stereotaxically implanted with bilateral cortical recording electrodes in all ip groups and cannula in the icv groups. Based on the previous study, an extract was obtained from the non-toxic and toxic honey. After the injection of the non-toxic or toxic honey extract, seizure stages and changes in EEG were evaluated from 9 am to noon. The icv administration of toxic honey extract produced stage 4 seizures and bilateral cortical spikes within 30-60 min and these effects disappeared after 120 min in Wistar rats or GAERS. The mean of bilateral cortical spike acitivity in EEG of Wistar rats was 804.2 ± 261.0 s in the 3-h period. After the icv administration of toxic honey extract to GAERS, the mean duration of spike-and-wave discharges (SWDs) in GAERS significantly decreased during the first 60 min and then returned to baseline level. Ip injection of toxic honey extract caused no seizure and no change in EEG in either GAERS or Wistars. These results suggest that the icv administration of toxic honey extract can be used as a seizure model.

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SummaryObjectives: We studied the electroencephalographic (EEG) and behavioral changes of the chemical model of generalized absence epilepsy induced by acute and chronic administration of gamma-butrolactone (GBL), a prodrug of gamma-hydroxybutyric acid. Methods: Adult male Wistar rats under anesthesia were implanted with bilateral cortical recording electrodes. The rats were administered 30 intraperitoneal injections of GBL twice daily from Monday to Friday and EEG was recorded 20 min before and 40 min after GBL injections. In order to monitor spontaneous spike-and-wave discharges (SWDs), the baseline EEGs on the subsequent Monday mornings after the first, second and third weekends were recorded for 90 min. Results: The intraperitoneal administration of GBL caused a rapid onset of bilaterally synchronous SWDs in the cortical EEG accompanied by behavioral immobility, vacant-staring and vibrissal twitching. By repeated GBL injections, animals displayed spontaneous bilateral synchronous SWDs in the baseline EEG on the Monday morning session after the GBL-free weekend period (60 h after the Friday afternoon injection). Conclusion:The present study reports the acute and chronic effects of the systemic administration of GBL. The chronic systemic application of GBL may represent a model of epileptogenesis for absence epilepsy.Key words: Absence epilepsy; gamma-butyrolactone; wistar rats; EEG. ÖzetAmaç: Çalışmamızda, gama-hidroksibutiratın (GHB) ön ilacı olan gama-butirolakton (GBL) ile indüklenmiş kimyasal jeneralize absans epilepsi modelinde GBL'nin akut ve kronik uygulanmasıyla oluşan EEG ve davranış değişiklikleri incelendi. Gereç ve Yöntem: Çalışmada kullanılan yetişkin Wistar sıçanlara, anestezi altında stereotaksik cerrahi yöntemi uygulandı; hayvanlara iki taraflı kortikal kayıt elektrotları implante edildi. Bir haftalık iyileşme sürecini takiben sabah ve akşam olmak üzere günde iki kez i.p. GBL enjeksiyonu uygulandı. Enjeksiyon uygulamasından önceki 20 dakika, sonrasında 40 dakika olmak üzere EEG kaydı alındı, enjeksiyon yapılmadan geçen haftasonlarını takiben Pazartesi sabahları enjeksiyon öncesi 40 dakika bazal EEG kaydı alındı. Bulgular: Bu çalışmada sistemik GBL uygulamasının akut ve kronik etkileri tekrar ortaya kondu. Çalışmamızda yer alan hayvanlarda, tekrarlayan enjeksiyonlarla birlikte, enjeksiyon yapılmadan geçen haftasonlarını takiben Pazartesi sabahları enjeksiyon öncesi alınan bazal kayıtlarda spontan iki taraflı DDD'leri görüldü.Sonuç: Kronik sistemik GBL uygulanması absans epilepsi için bir epileptogenez modeli ortaya koyabilir. GHB modeli antiepileptik ilaç araştır-malarında, absans epilepsi modeli olarak kullanılabilir.