Person: GÜLÇEBİ İDRİZ OĞLU, MEDİNE
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GÜLÇEBİ İDRİZ OĞLU
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MEDİNE
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Publication Open Access The pathways connecting the hippocampal formation, the thalamic reuniens nucleus and the thalamic reticular nucleus in the rat(WILEY, 2008-03) ONAT, FİLİZ; Cavdar, Safiye; Onat, Filiz Y.; Cakmak, Yusuf Oezguer; Yananli, Hasan R.; Gulcebi, Medine; Aker, RezzanMost dorsal thalamic nuclei send axons to specific areas of the neocortex and to specific sectors of the thalamic reticular nucleus; the neocortex then sends reciprocal connections back to the same thalamic nucleus, directly as well indirectly through a relay in the thalamic reticular nucleus. This can be regarded as a 'canonical' circuit of the sensory thalamus. For the pathways that link the thalamus and the hippocampal formation, only a few comparable connections have been described. The reuniens nucleus of the thalamus sends some of its major cortical efferents to the hippocampal formation. The present study shows that cells of the hippocampal formation as well as cells in the reuniens nucleus are retrogradely labelled following injections of horseradish peroxidase or fluoro-gold into the rostral part of the thalamic reticular nucleus in the rat. Within the hippocampal formation, labelled neurons were localized in the subiculum, predominantly on the ipsilateral side, with fewer neurons labelled contralaterally. Labelled neurons were seen in the hippocampal formation and nucleus reuniens only after injections made in the rostral thalamic reticular nucleus (1.6-1.8 mm caudal to bregma). In addition, the present study confirmed the presence of afferent connections to the rostral thalamic reticular nucleus from cortical (cingulate, orbital and infralimbic, retrosplenial and frontal), midline thalamic (paraventricular, anteromedial, centromedial and mediodorsal thalamic nuclei) and brainstem structures (substantia nigra pars reticularis, ventral tegmental area, periaqueductal grey, superior vestibular and pontine reticular nuclei). These results demonstrate a potential for the thalamo-hippocampal circuitry to influence the functional roles of the thalamic reticular nucleus, and show that thalamo-hippocampal connections resemble the circuitry that links the sensory thalamus and neocortex.Publication Open Access Electron microscopic GABA evaluation in hippocampal mossy terminals of genetic absence epilepsy rats receiving kindling stimulations(2022-12-01) KAYA, ÖZLEM TUĞÇE; TURGAN AŞIK, ZEHRA NUR; KARAMAHMUTOĞLU, TUĞBA; GÜLÇEBİ İDRİZ OĞLU, MEDİNE; AKAKIN, DİLEK; ŞİRVANCI, SERAP; İmdat N. N., KAYA Ö. T., TURGAN AŞIK Z. N., ERYİĞİT KARAMAHMUTOĞLU T., GÜLÇEBİ İDRİZ OĞLU M., AKAKIN D., ONAT F., ŞİRVANCI S.Objective: The hypotheses related to the fact of epileptic mechanisms are mainly based on excitation-inhibition imbalance in central nervous system. GAERS (Genetic Absence Epilepsy Rats from Strasbourg) is a well-known animal model of absence epilepsy, and frequently used in experimental studies. In the present study, we aimed to examine possible morphological and gamma-aminobutyric acid (GABA) density changes in GAERS hippocampus after electrical kindling stimulations. Methods: All control and test group rats received 6 kindling stimulations. Rats were decapitated 1 h after the last stimulation. Ultrastructural GABA immunocytochemistry was used to evaluate GABA density quantitatively in mossy terminals of hippocampal CA3 region. Results: GABA levels were less in kindling groups compared to their controls, and in GAERS groups compared to Wistar groups; mitochondrial and dendritic spine area ratios were greater in GAERS groups compared to Wistar groups, although all these evaluations were statistically nonsignificant. Depletion of synaptic vesicles was evident in the mossy terminals of kindling groups. Conclusion: The reason of decreased levels of GABA found in the present study might be that GABA has been released from the synaptic pool rapidly at an early time period after the last stimulation, for compansation mechanisms. Depletion of synaptic vesicles observed in kindling groups shows that even 6 kindling stimulations have an impact of changing hippocampal morphology in trisynaptic cycle. The increased mitochondrial area in GAERS might be related to the increased mitochondrial activity. The increased dendritic spine area might be related to the increased performance of learning in GAERS. Our findings indicating that absence epilepsy and temporal lobe epilepsy have different mechanisms of epileptogenesis might be a basis for further experimental studies.Publication Open Access The role of the substantia nigra pars reticulata in kindling resistance in rats with genetic absence epilepsy(WILEY, 2015-11) ONAT, FİLİZ; Akman, Ozlem; Gulcebi, Medine I.; Carcak, Nihan; Ozatman, Sema Ketenci; Eryigit, Tugba; Moshe, Solomon L.; Galanopoulou, Aristea S.; Onat, Filiz YilmazObjectiveGenetic Absence Epilepsy Rats from Strasbourg (GAERS) show a resistance to secondary generalization of focal limbic seizures evoked by kindling. The substantia nigra pars reticulata (SNR) is involved in the propagation and modulation of seizures in kindling. We first examined the role of the SNRanterior and SNRposterior subregions in the resistance to the development of kindling in GAERS. Subsequently, to determine whether kindling resistance relates to differential sensitivity of -aminobutyric acid -aminobutyric acid (GABA)ergic or dopaminergic SNR neurons to kindling, we studied the effects of kindling-inducing stimulations on parvalbumin (PRV; GABAergic neuron marker) or tyrosine hydroxylase (TH; dopaminergic neuron marker) immunoreactivity (ir), respectively, in GAERS and in nonepileptic control (NEC) Wistar rats that lack kindling resistance. MethodsAdult male GAERS were implanted with a stimulation electrode in the amygdala, and bilateral injection cannulas for lidocaine or saline injection (30 min before each kindling stimulation until the animals reached three stage 5 seizures or the 22 stimulations) into the SNRanterior or SNRposterior. In another experiment, PRV-ir in SNRanterior and SNRposterior and TH-ir in SNRposterior only were densitometrically compared in GAERS-SHAM, NEC-SHAM GAERS-STIM, and NEC-STIM animals (6 kindling stimulations). ResultsBilateral SNRposterior infusions of lidocaine eliminated the kindling resistance and resulted in stage 5 generalized motor seizures in all kindled rats. Bilateral lidocaine infusions in the SNRanterior failed to alter the kindling resistance in GAERS. PRV-ir in the SNRposterior was unaltered in GAERS-STIM but increased in NEC-STIM group. Cellular TH-ir in the SNRposterior significantly increased by kindling stimulations in both NEC-STIM and GAERS-STIM groups. SignificanceThe kindling resistance in GAERS is mediated by the SNRposterior in a lidocaine-sensitive manner. The insensitivity to kindling stimulation of PRV-ir in SNRposterior of GAERS but not NEC rats, implicate GABAergic SNRposterior neurons in kindling resistance. In contrast, the observed stimulation-specific increase in TH-ir in the SNRposterior is unrelated to kindling resistance.Publication Open Access The effect of serum levetiracetam concentrations on therapeutic response and IL1-beta concentration in patients with epilepsy(ELSEVIER SCIENCE BV, 2018-12) ONAT, FİLİZ; Gulcebi, Medine I.; Kendirli, Tansel; Turgan, Zehra Asik; Patsalos, Philip N.; Onat, Filiz YilmazObjective: Assessment of the relevance between serum drug concentration to its therapeutic response is a valid monitoring strategy for the clinical efficacy of antiepileptic drugs (AEDs). Levetiracetam (LEV) is a broad spectrum AED with a possible anti-inflammatory effect. We aimed to determine the relationship between LEV concentrations and its therapeutic response, and the effect of LEV on IL1-beta concentrations in patients with epilepsy. Methods: Patients on monotherapy (n = 7) or polytherapy (n = 15) with LEV for their seizures management were included. Blood samples of each patient were collected: just before LEV intake, 1 h, 2 h, 4 h and 8 h following the last dose. Serum LEV concentrations were measured by liquid chromatography mass spectrometry and IL1-beta concentrations by chemiluminescent immunometric assay. Concentration to dose (C/D) ratio values was used for analyses. LEV concentrations were compared between responders (<= 1 seizure/month) and non responders (> 1 seizure/month) and patients with or without adverse reactions. IL1-beta concentrations before and at 2 h following LEV ingestion were compared in order to detect the effect of the increase in serum LEV concentration on IL1-beta. Results: Although there was no change in LEV (C/D) ratio or LEV maximum concentration (Cmax)/D ratio of the responders and non-responders, the C/D ratio following 1 h of LEV intake (2.17 +/- 0.59 kg.day/L) and Cmax/D ratio (2.25 +/- 0.56 kg.day/L) in the patients with adverse effects was significantly higher than for the patients without adverse effects (1.09 +/- 0.12 kg.day/L and 1.49 +/- 0.14 kg.day/L respectively). A statistically significant decrease was found in the IL1-beta concentration to LEV (C/D) ratio with the increase in LEV concentration in patients on LEV monotherapy. Conclusion: The possible relationship between LEV Cmax and its therapeutic response or IL1-beta concentrations may be an importance indication of LEV antiepileptic efficacy. Consequently, monitoring LEV Cmax values may enhance LEV adherence because patients would be less likely to develop adverse effects.Publication Open Access Taking action on climate change: testimonials and position statement from the international league against epilepsy climate change commission(2023-03-01) GÜLÇEBİ İDRİZ OĞLU, MEDİNE; Aledo-Serrano A., Battaglia G., Blenkinsop S., Delanty N., Elbendary H. M., Eyal S., Guekht A., Gulcebi M., Henshall D. C., Hildebrand M. S., et al.The release of the 2021 Intergovernmental Panel on Climate Change (IPCC) report makes clear that human activities have resulted in significant alterations in global climate. There is no doubt that climate change is upon us; chronic global warming has been punctuated by more frequent extreme weather events. Humanity will have to mitigate climate change and adapt to these changing conditions or face dire consequences. One under-appreciated aspect of this global crisis is its impact on healthcare, particularly people with epilepsy and temperature-sensitive seizures. As members of the inaugural International League Against Epilepsy (ILAE) Climate Change Commission, we recount the personal motivations that have led each team member to decide to take action, in the hope that our journeys as ordinary clinicians and scientists will help persuade others that they too can act to foster change within their spheres of influence.Publication Open Access Thalamic branches of corticofugal axons from view of a critical eye and great mentor, Ray Guillery(WILEY) ONAT, FİLİZ; Onat, Filiz; Oglu, Medine Gulcebi Idriz; Cavdar, SafiyePublication Open Access The effect of prenatal and postnatal caffeine exposure on pentylentetrazole induced seizures in the non-epileptic and epileptic offsprings(2019-11-01) GÜLÇEBİ İDRİZ OĞLU, MEDİNE; ONAT, FİLİZ; YAVUZ M., Albayrak N., Ozgur M., Oglu M., Cavdar S., Onat F.Caffeine, a central nervous system stimulant, has been reported to modulate seizure activity in various studies. In this study the effects of caffeine exposure on the pentylenetetrazole (PTZ) induced seizure thresholds and seizure stages in the Wistar and genetic absence epilepsy model offsprings were examined. Adult female and male Wistar rats and genetic absence epilepsy rats from Strasbourg (GAERS) consumed caffeine dissolved in water (0.3 g/L) before conception, during the gestational periods and lactation period whereas control groups of each strain received tap water. All offsprings at postnatal day 30 (PN30) subjected to 70 mg/kg of PTZ were evaluated in terms of overall seizure stages, the latency to the first generalized seizure and the c-Fos protein activity in the brain regions of somatosensorial cortex (SSCx), reticular thalamic nucleus (Rt), ventrobasal thalamus (VB), centromedial nucleus (CM) and lateral geniculate nucleus (LGN). The Wistar caffeine group had significantly shorter latency to the first generalized seizure (1.53 +/- 0.49 min) comparing to the Wistar control offsprings (3.40 +/- 0.68 min). GAERS caffeine group (6.52 +/- 2.48 min) showed significantly longer latency comparing to Wistar caffeine group (1.53 +/- 0.49 min). Although statistically not significant, GAERS caffeine group showed a longer latency comparing to the GAERS control group (4.71 +/- 1.82 min). In all regions of SSCx, Rt, VB, CM and LGN, GAERS caffeine group had lower c-Fos protein expression comparing to the GAERS control group (p < 0.05). Wistar caffeine rats had lower expression of c-Fos protein comparing to the Wistar control group only in SSCx. In CM, GAERS rats expressed lower c-Fos protein comparing to the Wistar control (p < 0.05). In conclusion differential effects of caffeine in the seizure modulation may involve c-Fos protein activity-dependent protection mechanisms.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.Publication Open Access Does Feeding Behaviour of Genetic Absence Epilepsy Rats Differ from Control Wistar Rats(2012-09-30) GÜLÇEBİ İDRİZ OĞLU, MEDİNE; KARAMAHMUTOĞLU, TUĞBA; ONAT, FİLİZ; GÜLÇEBİ İDRİZ OĞLU M., KETENCİ S., KARAMAHMUTOĞLU T., AKIN D., ONAT F.