Person: ONAT, FİLİZ
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ONAT
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FİLİZ
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Publication Metadata only The relationship between age-related development of spike-and-wave discharges and the resistance to amygdaloid kindling in rats with genetic absence epilepsy(ACADEMIC PRESS INC ELSEVIER SCIENCE, 2008) ONAT, FİLİZ; Carcak, Nihan; Aker, Rezzan Guelhan; Oezdemir, Osman; Demiralp, Tamer; Onat, Filiz YilmazGenetic Absence Epilepsy Rats from Strasbourg (GAERS) are resistant to amygdaloid kindling. Since in GAERS the characteristics of spike-and-wave discharges (SWDs) change with age, we have studied the relation between SWD maturation and the development of kindling resistance. Non-epileptic Wistar rats and GAERS were stimulated in basolateral amygdala with 400 mu A at 20 min intervals until they reached stage 5 seizures or for a maximum of 36 stimulations. All of the Wistar rats, the postnatal (PN) day 20 GAERS and the (kindling-prone) subgroups of GAERS at PN30 and PN60 reached stage 5 seizures; at PN20, PN30 and PN60 kindling rates were significantly slower in GAERS compared to Wistar rats. At PN30 and PN60, 41% and 69% of GAERS, respectively, showed no stage 3, 4 or 5 seizures after 36 stimulations (kindling-resistant subgroups). The SWD maturation involves changes in spectral patterns and correlate with age-related increases in kindling resistance in GAERS. (C) 2008 Elsevier Inc. All rights reserved.Publication Open Access Effect of stage 2 kindling on local cerebral blood flow rates in rats with genetic absence epilepsy(WILEY, 2009-01) ONAT, FİLİZ; Carcak, Nihan; Ferrandon, Arielle; Koning, Estelle; Aker, Rezzan Guelhan; Oezdemir, Osman; Onat, Filiz Yilmaz; Nehlig, AstridGenetic absence epilepsy rats from Strasbourg (GAERS) are resistant to the progression of kindling seizures. We studied local cerebral blood flow (LCBF) changes in brain regions involved in seizures in both GAERS and nonepileptic rats (NEC) to map the differences that may be related to the resistance to kindling. Electrodes were implanted in the amygdala of adult NEC and GAERS male rats, which were stimulated to reach stage 2. Quantitative autoradiographic measurements of LCBF were performed by the [C-14]-iodoantipyrine ([C-14]IAP) autoradiographic technique allowing the precise mapping of regional perfusion changes. LCBF rates were measured bilaterally in 43 brain regions. The tracer infusion lasted for 60 s and started at 15 s before seizure induction. Rates of LCBF increased in stimulated GAERS and NEC groups compared to nonstimulated controls. The LCBF increase in stimulated GAERS was larger and more widespread than that observed in stimulated NEC. The LCBF increase in the somatosensory cortex, ventrobasal and anterior thalamic nuclei, hypothalamus, subthalamic nucleus, piriform, entorhinal and perirhinal cortex, amygdala, CA2 region of hippocampus, and substantia nigra was statistically significantly larger in stimulated GAERS compared to stimulated NEC rats. The results show that more brain regions are activated by kindling stimulation in GAERS. This widespread activation in GAERS involves the somatosensory cortex and thalamus, which are both known to be involved in the expression of absence seizures as well as numerous limbic regions thought not to play a role in the expression of absence seizures, suggesting an interaction between corticothalamocortical and limbic circuitries.Publication Metadata only GABA(A) receptor mediated transmission in the thalamic reticular nucleus of rats with genetic absence epilepsy shows regional differences: Functional implications(ELSEVIER SCIENCE BV, 2006) ONAT, FİLİZ; Aker, Rezzan Gulhan; Ozyurt, Hazan B.; Yananli, Hasan R.; Cakmak, Yusuf Ozgur; Ozkaynakci, Aydan E.; Sehirli, Umit; Saka, Erdinc; Cavdar, Safiye; Onat, Filiz YimazThe aim of the present study was to investigate the effect of local injections of the GABA(A) receptor antagonist, bicuculline, into the rostral and caudal parts of the thalamic reticular nucleus (TRN), on the generation of spike-and-wave discharges in Genetic Absence Epilepsy Rats from Strasbourg (GAERS). Spike-and-wave discharges are important in the pathophysiology of absence epilepsy and generated by the cortico-thalamo-cortical pathway, where GABA has a significant role, particularly in the TRN. Artificial cerebrospinal fluid or bicuculline was administered to rostral or caudal parts of TRN of GAERS through a stereotaxically placed guide cannula. Administration of bicuculline produced opposite effects according to the injection site. Administration into the caudal TRN produced statistically significant increases in the duration of spike-and-wave discharges, whereas injections into the rostral TRN produced significant decreases. Correspondingly, distinct patterns of afferent connections have been demonstrated with the wheat-germ-agglutinin horseradish peroxidase (WGA-HRP) retrograde tracing method in control non-epileptic rats and GAERS for the rostral and caudal parts of the TRN. Injection of WGA-HRP tracer showed no detectable difference regarding the rostral and caudal connections between GAERS and Wistar animals. Rostral parts of TRN have thalamic and cortical connections that are primarily motor and limbic whereas for the caudal parts these connections are primarily sensory. Further, the rostral parts receive inputs from the substantia nigra pars reticularis and the ventral pallidum that the caudal part lacks. The extent to which these connectional differences may be responsible for the functional differences demonstrated by the bicucculine injections remains to be explored. (c) 2006 Elsevier B.V. All rights reserved.Publication Metadata only Hippocampal kindling in rats with absence epilepsy resembles amygdaloid kindling(ELSEVIER, 2008) ONAT, FİLİZ; Akman, Ozlem; Karson, Ayse; Aker, Rezzan Gulhan; Ates, Nurbay; Onat, Filiz YilmazPurpose: WAG/Rij and GAERS rats show delays or resistance to secondary generalization of limbic seizures during amygdaloid kindling. In this study, we aimed to evaluate the kindling from a different limbic site, hippocampus, and to compare its effects on spike-and-wave discharges (SWDs) with that of amygdaloid kindling. Methods: Recording electrodes were implanted epidurally and a stimulation/recording electrode was implanted into the ventral hippocampus in the WAG/Rij, GAERS and Wistar rats. Animals received kindling stimulation twice daily at their afterdischarge thresholds until they reached stage 5 seizures, or the maximum number of stimulations (50) had been delivered. The EEG was recorded to analyze SWDs and afterdischarge durations. Results: All Wistar rats reached stage 5 by the 34th stimulation. 4 of 8 WAG/Rij rats and 3 of 6 GAERS rats displayed stage 4/5 seizures (kindling-prone rats); the rest stayed at stage 2 seizures (kindling-resistant rats) even after 50th stimulations. The cumulative duration and number of SWDs decreased in the post-stimulation period after the first stage 2 seizures, whereas these parameters increased after the first stage 3 seizures in the kindling-prone WAG/Rij and GAERS. The peak frequency of SWDs and its harmonics decreased significantly only in the GAERS group after stage 4 seizures. Conclusion: Hippocampal kindling resembles amygdaloid kindling in showing a delay of or resistance to secondary seizure generalization, which supported the interaction of thalamo-cortical and limbic circuitry in GAERS and WAG/Rij. (C) 2008 Elsevier B.V. All rights reserved.Publication Metadata only Localized cortical injections of ethosuximide suppress spike-and-wave activity and reduce the resistance to kindling in genetic absence epilepsy rats (GAERS)(ELSEVIER, 2010) ONAT, FİLİZ; Aker, Rezzan Guelhan; Tezcan, Kutluhan; Carcak, Nihan; Sakalli, Eren; Akin, Demet; Onat, Filiz YilmazModels of genetic absence epilepsy are resistant to secondary generalization of focal limbic seizures. This correlates with the postnatal development of spike-and-wave discharges (SWDs), a hallmark of absence seizures arising from a cortical focus in the perioral region of somatosensory cortex. Ethosuximide injected at this site suppresses SWDs. The effect of this suppression on kindling in Genetic Absence Epilepsy Rats from Strasbourg (GAERS), has been compared for postnatal 30 day (PN30) rats having immature SWDs and adult (>4 months) rats having mature SWDs. Non-epileptic Wistar and GAERS rats were implanted with a basolateral amygdaloid stimulation electrode, bilateral injection cannulas into the cortical perioral focus, and cortical recording electrodes. Following recovery cortical injections of ethosuximide or saline were made and after 30 min rats were given 36 stimulations or until Racine's stage 5 seizures were produced. All Wistar rats (PN30 and adult) treated with saline or ethosuximide reached stage 5. Of GAERS given saline, 33% (PN30) and 43% (adults) were resistant to kindling; after ethosuximide pups behaved like Wistars, but adults showed a delay in kindling relative to Wistars. These findings imply that mechanisms underlying kindling resistance are related but not limited to SWD activity in animals with genetic absence epilepsy. (C) 2009 Elsevier B.V. All rights reserved.Publication Metadata only GABA and L-glutamic acid release in en bloc resection slices of human hippocampus: an in vitro microdialysis study(SPRINGER-VERLAG ITALIA SRL, 2001) ONAT, FİLİZ; Goren, MZ; Onat, F; Ozkara, C; Ozyurt, E; Eskazan, E; Aker, RThe interaction of neurotransmitters has been a major interest in pathophysiological conditions like epilepsy. In vivo microdialysis has recently gained much validity in measuring neurotransmitter release in experimental animals. However, there is a paucity of data concerning its use in humans on the grounds of safety considerations. Microdialysis experiments were performed using die hippocampal head region removed from patients with medically intractable seizures, who underwent surgery for mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). Following en bloc resection, the tissues were immediately transferred to the essential in vitro milieu. Slices were incubated in lactated Ringer's solution and microdialysis probes inserted into the slices were perfused with artificial cerebrospinal fluid (aCSF). When the K+ concentration of aCSF was elevated to 100 mM, GABA and L-glutamic acid levels increased by 293% and 177%, respectively. This method may serve as an experimental model for human brain, to throw more light on the interactions between GABA and L-glutamic acid in hippocampal tissues obtained from patients with MTLE-HS.Publication Metadata only Increased inhibitory synaptic activity in the hippocampus (CA1) of genetic absence epilepsy rats: Relevance of kindling resistance(ELSEVIER, 2016) ONAT, FİLİZ; Carcak, Nihan; Dilekoz, Ergin; Gulhan, Rezzan; Onur, Rustu; Onat, Filiz Yilmaz; Sara, YildirimPurpose: Genetic absence epilepsy rats from Strasbourg (GAERS), a well-validated genetic rat model for typical absence epilepsy, are known to manifest a resistance to secondary generalization of abnormal focal electrical activity evoked by kindling. The mechanism of this resistance is still unclear. In order to understand the possible mechanism of kindling resistance, we investigated for the first time, the differences of short-term synaptic plasticity by using a paired-pulse paradigm as an indicator of GABAergic activity in CM region of hippocampus in GAERS and non-epileptic Wistar rats in-vivo. Methods: Rats were subjected to kindling process, basolateral amygdala was stimulated twice a day, with a supra-threshold current, until they displayed limbic or convulsive seizures. One hour after the last kindling stimulation, evoked field potentials from CA1 pyramidal layer of hippocampus were recorded in-vivo under urethane anesthesia. Results: In response to supra-threshold kindling stimulations GAERS showed a significantly delayed kindling progression and displayed a significant increase in hippocampal excitability at early stages of kindling that is the critical for the development of convulsive seizures. In control rats that were not received kindling stimulation, paired-pulse depression (PPD) was significantly pronounced in GAERS with respect to the Wistar group. During the kindling course, PPD was gradually reduced in the Wistar rats as kindling progression was advanced. However in GAERS, PPD ratios were not significantly changed at early stages of kindling. When GAERS reached convulsive stage, their PPD ratios became similar to that of Wistar rats. Discussion: The increased inhibition in paired-pulse responses at early stages of kindling in GAERS suggests the role of augmented GABAergic activity as one of the underlying mechanisms of kindling resistance observed in genetic rat models of absence epilepsy. (C) 2016 Published by Elsevier B.V.Publication Metadata only IL-1 beta is induced in reactive astrocytes in the somatosensory cortex of rats with genetic absence epilepsy at the onset of spike-and-wave discharges, and contributes to their occurrence(ACADEMIC PRESS INC ELSEVIER SCIENCE, 2011) ONAT, FİLİZ; Akin, Demet; Ravizza, Teresa; Maroso, Mattia; Carcak, Nihan; Eryigit, Tugba; Vanzulli, Ilaria; Aker, Rezzan Gulhan; Vezzani, Annamaria; Onat, Filiz YilmazInterleukin (IL)-1 beta plays a crucial role in the mechanisms of limbic seizures in rodent models of temporal lobe epilepsy. We addressed whether activation of the IL-1 beta signaling occurs in rats with genetic absence epilepsy (GAERS) during the development of spike-and-wave discharges (SWDs). Moreover, we studied whether inhibition of IL-1 beta biosynthesis in GAERS could affect SWD activity. IL-1 beta expression and glia activation were studied by immunocytochemistry in the forebrain of GAERS at postnatal days (PN)14, PN20, and PN90 and in age-matched non-epileptic control Wistar rats. In PN14 GAERS, when no SWDs have developed yet. UT immunostaining was undetectable, and astrocytes and microglia showed a resting phenotype similar to control Wistar rats. In 3 out of 9 PN20 GAERS, IL-1 beta was observed in activated astrocytes of the somatosensory cortex; the cytokine expression was associated with the occurrence of immature-type of SWDs. In all adult PN90 GAERS, when mature SWDs are established, IL-1 beta was observed in reactive astrocytes of the somatosensory cortex but not in adjacent cortical areas or in extra-cortical regions. An age-dependent c-fos activation was found in the somatosensory cortex of GAERS with maximal levels reached in PN90 rats; c-fos was also induced in some thalamic nuclei in PN20 and PN90 GAERS. Inhibition of IL-1 beta biosynthesis in PN90 GAERS by 4-day systemic administration of a specific ICE/Caspase-1 blocker, significantly reduced both SWD number and duration. These results show that IL-1 beta is induced in reactive astrocytes of the somatosensory cortex of GAERS at the onset of SWDs. IL-1 beta has pro-ictogenic properties in this model, and thus it may play a contributing role in the mechanisms underlying the occurrence of absence seizures. (C) 2011 Elsevier Inc. All rights reserved.