Person: KARAMAHMUTOĞLU, TUĞBA
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KARAMAHMUTOĞLU
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TUĞBA
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Publication Metadata only Suppressive effect of Rho-kinase inhibitors Y-27632 and fasudil on spike-and-wave discharges in genetic absence epilepsy rats from Strasbourg (GAERS)(SPRINGER, 2018) ONAT, FİLİZ; Carcak, Nihan; Yavuz, Melis; Karamahmutoglu, Tugba Eryigit; Kurt, Akif Hakan; Kucuk, Meral Urhan; Onat, Filiz Yilmaz; Buyukafsar, KansuRho/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 (1-10mg/kg for Y-27632 or fasudil) or intracerebroventricular injection (7-20nmol/5l for Y-27632 or 10-100nmol/5l 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.Publication Metadata only Electroencephalographic and behavioral effects of intracerebroventricular or intraperitoneal injections of toxic honey extract in adult Wistar rats and GAERS(SPRINGER-VERLAG ITALIA SRL, 2014) ONAT, FİLİZ; Kuru, Pinar; Torun, Merve; Halac, Hande Melike; Temiz, Gozde; Iskender, Ece; Karamahmutoglu, Tugba; Idrizoglu, Medine Gulcebi; Onat, Filiz YilmazToxic 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 +/- A 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.Publication Metadata only Ultrastructural GABA immunocytochemistry in the mossy fiber terminals of Wistar and genetic absence epileptic rats receiving amygdaloid kindling stimulations(ELSEVIER, 2011) AKAKIN, DİLEK; Akakin, Dilek; Sirvanci, Serap; Gurbanova, Ayten; Aker, Rezzan; Onat, Filiz; San, TangulThe existence of absence epilepsy and temporal lobe epilepsy in the same patient is not common in clinical practice. The reason why both types of seizures are rarely seen in the same patient is not well understood. Therefore, we aimed to investigate kindling in a well known model of human absence epilepsy, genetic absence epilepsy rats from Strasbourg (GAERS). In the present study, we analyzed whether the GABA content of GAERS that received kindling stimulations was altered in the hippocampal mossy fiber terminals compared to non-epileptic control (NEC) Wistar rats. For this purpose, we used an immunocytochemical technique at the ultrastructural level. Ultrathin sections were immunolabeled with anti-GABA antibody and transmission electron microscopy was used for the ultrastructural examination. The number of gold particles per nerve terminal was counted and the area of the nerve terminal was determined using NIH image analysis program. The GABA density was found to be higher in sham-operated GAERS than sham-operated Wistar rats. The density was increased in kindling Wistar group compared to sham-operated Wistar and kindling GAERS groups. No statistical difference was observed between sham-operated GAERS and kindling GAERS groups. The increase in GABA levels in stimulated Wistar rats may be a result of a protective mechanism. Furthermore, there may be strain differences between Wistar rats and GAERS and our findings addressing different epileptogenesis mechanisms in these strains might be a basis for future experimental studies. (C) 2010 Elsevier B.V. All rights reserved.