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 Open Access Effects of Probiotic Consumption on Absence Seizures(KARE PUBL, 2017) ONAT, FİLİZ; Akkol, Serdar; Dogan, Mehmet Can; Esenkar, Duygu; Dogan, Handan; Karamahmutoglu, Tugba; Onat, FilizObjectives: Probiotics are microorganisms of intestinal microflora that are beneficial for human health. Childhood absence epilepsy has 2 validated rat models: Genetic Absence Epilepsy Rats from Strasbourg (GAERS) and Wistar Albino Glaxo from Rijswijk (WAG/Rij). To date, there have been no clinical or experimental studies of the effects of probiotics on absence epilepsy. The present study was an investigation of the effects of probiotics on absence seizures in the GAERS rat model. Methods: GAERS were used to examine the effects of probiotics. Nine male GAERS were assigned to 1 of 2 groups (probiotic or control). The animals had free access to food and water. Commercially available probiotic product was provided in drinking water to probiotic group for 1 month. Surface electrodes were then implanted for electroencephalogram (EEG) recordings. Two aspects of EEG recordings were compared: cumulative duration and cumulative number of absence seizures. Results: Analysis of spike-and-wave discharges between the 2 groups showed no significant difference in either cumulative duration or number (p>0.05). Additionally, it was observed that probiotic group consumed more water than control group (p<0.05). Conclusion: Results indicated that probiotic consumption had no effect on duration or number of spike-and-wave discharges of GAERS after 1-month feeding period. This is the first investigation in the literature addressing interactions between probiotics and absence epilepsy, and further research is needed.Publication Metadata only Ultrastructural GABA immunogold labeling in the substantia nigra pars reticulata of kindled genetic absence epilepsy rats(TAYLOR & FRANCIS INC, 2020) AKAKIN, DİLEK; Sirvanci, Serap; Akakin, Dilek; Idrizoglu, Medine Gulcebi; Kaya, Ozlem Tugce; Karamahmutoglu, Tugba; Asik, Zehra Nur Turgan; Onat, FilizGenetic Absence Epilepsy Rats from Strasbourg (GAERS) is a well-known animal model of absence epilepsy and they are resistant to electrical kindling stimulations. The present study aimed to examine possible differences in gamma-aminobutyric acid (GABA) levels and synapse counts in the substantia nigra pars reticulata anterior (SNRa) and posterior (SNRp) regions between GAERS and Wistar rats receiving kindling stimulations. Animals in the kindling group either received six stimulations in the amygdala and had grade 2 seizures or they were kindled, having grade five seizures. Rats were decapitated one hour after the last stimulation. SNR regions were obtained after vibratome sectioning of the brain tissue. GABA immunoreactivity was detected by immunogold method and synapses were counted. Sections were observed by transmission electron microscope and analyzed by Image J program. GABA density in the SNRa region of fully kindled GAERS and Wistar groups increased significantly compared to that of their corresponding grade 2 groups. The number of synapses increased significantly in kindled and grade 2 GAERS groups, compared to kindled and grade 2 Wistar groups, respectively, in the SNRa region. GABA density in the SNRp region of kindled GAERS group increased significantly compared to that of GAERS grade 2 group. In the SNRp region, both kindled and grade 2 GAERS groups were found to have increased number of synapses compared to that of GAERS control group. We concluded that both SNRa and SNRp regions may be important in modulating resistance of GAERS to kindling stimulations.Publication Open Access Evaluation of GAD67 immunoreactivity in the region of substantia nigra pars reticulata in resistance to development of convulsive seizure in genetic absence epilepsy rats(KARE PUBL, 2016) ONAT, FİLİZ; Gulcebi, Medine; Akman, Ozlem; Carcak, Nihan; Karamahmutoglu, Tugba; Onat, FilizOBJECTIVE: Nonconvulsive absence epilepsy and convulsive epilepsy seizures are rarely seen in the same patient. It has been demonstrated that there is a resistance to development of convulsive seizures in genetic absence epilepsy models. The present study investigated glutamic acid decarboxylase (GAD) immunoreactivity in the brain region related to the interaction of these two seizure types, namely substantia nigra pars reticulata (SNR) subregions, SNRantenor and SNRpostenor. METHODS: Nonepileptic adult male Wistar rats and Genetic Absence Epilepsy Rats from Strasbourg (GAERS) were used. Experimental groups of Wistar and GAERS were electrically stimulated for kindling model to induce convulsive epileptic seizures. An electrical stimulation cannula was stereotaxically implanted to the basolateral amygdala and recording electrodes were placed on the cortex. Sagittal sections of SNR were used to evaluate immunohistochemical reaction. Sections were incubated with anti-GAD67 antibody. Densitometric analysis of GAD67 immunoreactive neurons was performed using photographs of stained sections. One-way analysis of variance and post hoc Bonferroni test were used for statistical analysis of the data. RESULTS: There was no difference in GAD67 immunoreactivity of SNR subregions of control Wistar and control GAERS. An increase in GAD67 immunoreactivity was detected in SNRposterior subregion of stimulated Wistar rats, whereas there was a decrease in GAD67 immunoreactivity in SNRposterior of stimulated GAERS. The difference in GAD67 immunoreactivity between these two groups was statistically significant. CONCLUSION: Level of synthetized gamma-aminobutyric acid in SNRposterior subregion plays an important role in the interaction of nonconvulsive absence epilepsy seizures and convulsive epilepsy seizures.