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GÜLHAN, REZZAN

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End date: 2009 × Subject: GAERS ×

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    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 Yilmaz
    Genetic 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.
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    PublicationOpen Access
    Amygdala kindling in the WAG/Rij rat model of absence epilepsy
    (WILEY, 2006-01) ONAT, FİLİZ; Aker, RG; Yananli, HR; Gurbanova, AA; Ozkaynakci, AE; Ates, N; van Luijtelaar, G; Onat, FY
    Purpose: The kindling model in rats with genetic absence epilepsy is suitable for studying mechanisms involved in the propagation and generalization of seizure activity in the convulsive and nonconvulsive components of epilepsy. In the present study, we compared the amygdala kindling rate and afterdischarge characteristics of the nonepileptic Wistar control rat with a well-validated model of absence epilepsy, the WAG/Rij rat, and demonstrated the effect of amygdala kindling on spike-and-wave discharges (SWDs) in the WAG/Rij group. Methods: Electrodes were stereotaxically implanted into the basolateral amygdala of rats for stimulation and recording and into the cortex for recording. After a recovery period, the animals were stimulated at their afterdischarge thresholds. EEG was recorded to analyze SWDs and afterdischarge durations. The seizure severity was evaluated by using Racine's 5-stage scale. Results: All nonepileptic control and four of seven WAG/Rij animals reached a stage 5 seizure state, whereas three animals failed to reach stage 3, 4, or 5 and stayed at stage 2 after application of 30 stimulations. Interestingly, WAG/Rij rats, resistant to kindling, demonstrated a significantly longer duration of SWDs on the first day of the experiment before kindling stimulation than did the kindled WAG/Rij animals. Additionally, the cumulative total duration and the number of SWDs after the kindling stimulation were statistically increased compared with SWDs before kindling stimulation. Conclusions: The results of our study demonstrate that the progress of amygdala kindling is changed in rats with genetic absence epilepsy, perhaps as a consequence of the hundreds of daily SWDs.
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    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 Yimaz
    The 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.
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    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 Yilmaz
    Purpose: 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.
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    Resistance to propagation of amygdaloid kindling seizures in rats with genetic absence epilepsy
    (BLACKWELL PUBLISHING INC, 2002) ONAT, FİLİZ; Eskazan, E; Onat, FY; Aker, R; Oner, G
    Purpose: The existence of absence epilepsy and temporal partial seizure pattern in the same patient is an uncommon state. In the present study, we aimed to evaluate whether the process of kindling as a model of complex partial seizures with secondary generalization is altered in rats with genetic absence epilepsy. Methods: Six- to 12-month-old nonepileptic control Wistar rats and genetic absence epileptic rats from Strasbourg (GAERS) were used in the experiments. One week before the experiments, bilateral stimulation and recording electrodes were implanted stereotaxically into the basolateral amygdala and cortex, respectively. Animals were stimulated at their afterdischarge threshold current twice daily for the process of kindling and accepted as fully kindled after the occurrence of five grade 5 seizures. Bilateral EEGs from amygdala and cortex were recorded continuously during 20 min before and 40 min after each stimulus. Results: All control Wistar rats were fully kindled after stimulus 12 to 15. Although the maximal number of stimulations had been applied, GAERS remained at stage 2, and no motor seizures were observed. The afterdischarge duration in bilateral amygdala and the cortex after the kindling stimulus was shorter in GAERS when compared with control rats. Conclusions: Occurrence of only grade 2 seizures and no observation of grade 3-5 seizures in GAERS with the maximal number of stimulations would suggest that the generalized absence seizures may be the reason of the resistance in the secondary generalization of limbic seizures during amygdala kindling.
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    PublicationOpen Access
    The effect of generalized absence seizures on the progression of kindling in the rat
    (BLACKWELL PUBLISHING, 2007-09) ONAT, FİLİZ; Onat, Filiz Yilmaz; Aker, Rezzan Guelhan; Gurbanova, Ayten Azizova; Ates, Nurbay; van Luijtelaar, Gilles
    The involvement of the thalamus in limbic epileptogenesis has recently drawn attention to the connectivity between the nuclei of the thalamus and limbic structures. Thalamo-limbic circuits are thought to regulate limbic seizure activity whereas thalamocortical circuits are involved in the expression and generation of spike-and-wave discharges (SWDs) in the absence epilepsy models. Genetic Absence Epilepsy Rats From Strasbourg (GAERS) and WAG/Rij (Wistar Albino Glaxo from Rijswijk) are well-defined genetic animal models of absence epilepsy. We aimed to examine the duration of behavioral changes in the kindling process and the relation of SWD activity to the kindling progress in the GAERS and WAG/Rij animals. Electrodes were stereotaxically implanted into the basolateral amygdala and the cortex of rats for stimulation and recording. The animals were stimulated at the threshold for producing afterdischarges. EEG was recorded to analyze SWDs and afterdischarge durations. The seizure severity was evaluated using Racine's 5-stage scale. None of the GAERS animals reached stage 3, 4, or 5 after application of 30 stimulations. The WAG/Rij animals showed different rate of kindling, therefore they were further categorized into the kindling-resistant, slow-kindled, and rapid-kindled groups. The kindling-resistant animals demonstrated a significantly longer duration of SWDs on the first day of the experiment before kindling stimulation and shorter duration of afterdischarge than did the kindled WAG/Rij animals. Behavioral durations at stage 2 were longer in kindled Wistar and WAG/Rij animals compared to kindling-resistant WAG/Rij and GAERS. These results suggest that mechanisms involved in the generation of SWDs act as a counterbalance to the excitability induced by kindling.
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    Genetik absans epilepsili sıçanlarda kortikal odağa etosüksimid uygulamasının kindling üzerine etkisi
    (2009-11-04) GÜLHAN, REZZAN; ONAT, FİLİZ; ÇARÇAK YILMAZ N., GÜLHAN R., ONAT F.
    Genetik absans epilepsi modellerinde fokal limbik nöbetlerin sekonder jenerelizasyonuna direnç olduğu ve diken-dalga deşarj aktivitesinin kindling uyarılarından etkilendiği gösterilmiştir. Diken-dalga deşarj aktivitesinin somato-sensoriyal korteksin perioral bölgesinde bir odaktan köken aldığı ve kortikal odağa etosüksimid enjeksiyonları ile bu deşarjların baskılandığı bilinmektedir. Bu çalışmada 30 günlük Strasbourg kökenli genetik absans epilepsili sıçanlarda (GAERS), diken-dalga deşarj odağının etosüksimid ile baskılanmasının, limbik epilepsi modeli olan kindling gelişimine etkisi incelenmiştir. Bu amaçla GAERS’lere stereotaksik cerrahi ile sağ bazolateral amigdalaya uyarı elektrodu, kortikal odağa bilateral enjeksiyon kanülü ve kortekse kayıt elektrodları yerleştirilmiştir. Cerrahi sonrasında bir günlük dinlenme süresinin ardından bazal EEG kaydı alınmış ve kindling deneyleri için artdeşarj eşiği belirlenmiştir. Bu işlemi takiben hayvanların sağ ve sol kortekslerine bilateral etosüksimid enjeksiyonu yapılmış ve daha sonra 20 dk’da bir 400 mikroA şiddetinde olacak şekilde elektriksel olarak uyarılmışlardır. Elektriksel uyarılar sıçanlar Racine’in skalasına göre 5. evre nöbet geçirene kadar tekrarlanmış ya da maksimum 36. uyarıya ulaşılması hedeflenmiştir. Diken-dalga deşarjları ve uyarı sonrası artdeşarj süreleri hesaplanmış, oluşan davranış değişiklikleri değerlendirilmiştir. Etosüksimid uygulanan 30 günlük GAERS’lerde diken-dalga deşarj sayı ve süresi enjeksiyonu takip eden 20. dakikadan itibaren anlamlı derecede baskılanmış ve hayvanların hepsi 5. evre nöbet geçirmişlerdir. Bununla birlikte GAERS grubunda ilk defa 4. ve 5. evre nöbet geçirmek için verilmesi gereken uyarı sayısı kontrol grubuna göre anlamlı derecede fazla bulunmuştur. Bu sonuçlar ile diken-dalga aktivitesinin kaynağı olan kortikal odak baskılandığında, fokal limbik nöbetlerin sekonder jenerelizasyonuna direncin ortadan kalktığı gösterilmiştir. Bu durum absans epilepside limbik epilepsiye direnç mekanizmalarının diken-dalga aktivitesi ile ilişkili olduğunu göstermektedir.