Person: GÜLHAN, REZZAN
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GÜLHAN
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REZZAN
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Publication Metadata only Effect of U-92032, T-Type Ca(2+)Channel Blocker, on Rats with Genetic Absence Epilepsy(KARGER, 2020) YANANLI, HASAN RACİ; Yananli, Hasan Raci; Demirkapu, Mahluga Jafarova; Sakalli, Halil Eren; Gulhan, Rezzan; Onat, Filiz YilmazIntroduction:Absence epilepsy is associated with diffuse spike-and-wave discharges (SWD) on the electroencephalogram (EEG). Recent studies have demonstrated that the primary somatosensory cortex is also implicated in the generation of the SWDs.Objective:This study investigated the effects of systemic and local administrations of U-92032 into the brain of Genetic Absence Epilepsy Rats from Strasbourg (GAERS).Methods:GAERS animals underwent stereotaxic surgery for the placement of EEG recording electrodes and guide cannulas for U-92032 administration into the lateral ventricle (intracerebroventricular [i.c.v.]), upper lips area (S1Ulp) or barrel field area (S1B) of primary somatosensory cortex. Following 7 days of recovery, electrical activity was recorded continuously for 1 h before and 6 h after intraperitoneal (0.25; 1; 5 mg/kg i.p.) or local U-92032 or dimethyl sulfoxide (DMSO) injections.Results:No changes were detected in the cumulative duration, mean duration, and number of SWDs following i.p. U-92032 injections. Local i.c.v. injections of U-92032 caused a significant decrease in the cumulative duration (i.c.v., 50 and 100 nmol/L), mean duration (i.c.v., 50, 100, and 250 nmol/L), and the number (i.c.v., 250 nmol/L) of SWDs compared to DMSO groups. Intra-cortical (S1Ulp and S1B) U-92032 injections caused a significant decrease in all 3 parameters compared to DMSO groups, as well.Conclusion:Intra-cortical injection of U-92032 caused almost complete removal of SWDs in GAERS and i.c.v. administration resulted in a significant reduction. However, systemic i.p. administration did not cause a significant change with the applied -doses.Publication Metadata only Extracellular concentrations of catecholamines and amino acids in the dorsomedial hypothalamus of kindled rats - A Microdialysis Study(KARGER, 2003) ONAT, FİLİZ; Goren, MZ; Aker, R; Yananli, HR; Onat, FYEpilepsy affects homeostasis and autonomic nervous system functions. It has been thought that the dysfunction in the autonomic neural mechanisms could be a cause of sudden unexpected death in patients with epilepsy. The kindling model of epilepsy is considered to be an animal model for complex partial seizures with secondary generalization. The objectives of this study were to investigate the extracellular gamma-aminobutyric acid (GABA), glutamate, noradrenaline and dopamine levels in the dorsomedial nucleus of the hypothalamus in nonepileptic and kindled epileptic rats and to explain some of the cardiovascular changes in the kindling model of epilepsy. Stimulation electrodes were stereotaxically implanted into the basolateral amygdala and electrical stimulation was applied 3 times a day at a constant current. The rats were then kindled to full stage 5 seizures. Microdialysis experiments were performed to demonstrate the neurotransmitter levels in the dorsomedial nucleus of the hypothalamus 3-5 days after being kindled. Decreases in noradrenaline and dopamine levels in the dorsomedial nucleus were detected in the conscious kindled animals. This finding is in agreement with prior findings that the noradrenergic system has a negative role in the process of kindling. The basal level of glutamic acid and GABA remained unchanged in the kindled group when compared to non-epileptic animals, and similarly, neither blood pressure nor heart rate responses to bicuculline or N-methyl-D-aspartate were affected by the acute kindled state. These findings suggest that the autonomic changes in kindling require further studies. Copyright (C) 2003 S. Karger AG, Basel.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 The effect of telmisartan, an angiotensin receptor blocker, on alcohol consumption and alcohol-induced dopamine release in the nucleus accumbens(ELSEVIER SCIENCE INC, 2020) YANANLI, HASAN RACİ; Tezcan, Kutluhan; Yananli, Hasan Raci; Demirkapu, Mahluga Jafarova; Goren, M. Zafer; Sakalli, H. Eren; Colombo, Giancarlo; Gulhan, RezzanAlcohol use disorder remains a major health problem. The mesocorticolimbic dopaminergic system, including the nucleus accumbens region and multiple neural circuits, is involved in its complex underlying mechanism. For instance, alcohol intake stimulates the central and peripheral renin-angiotensin system and increases angiotensin II levels, which predominantly affect angiotensin 1 receptors both in the periphery and in the brain. In this study, we aimed to investigate the effects of the intracerebroventricularly-administered angiotensin 1 receptor blocker telmisartan on the alcohol consumption of male Sardinian alcohol-preferring (sP) rats and on the alcohol-induced dopamine levels in the nucleus accumbens region in Wistar rats. Acute intracerebroventricular administration of telmisartan (100 nM) reduced the alcohol intake for 24 hours without affecting food and water consumption in sP rats. Acute intracerebroventricular injection of the opioid receptor antagonist naloxone (75 nM), tested as a reference compound, also reduced the alcohol consumption in sP rats; however, naloxone's effect lasted only for 30 minutes. In microdialysis experiments, telmisartan administered intracerebroventricularly did not change dopamine levels in the nucleus accumbens that had been induced by acute intraperitoneal alcohol administration in Wistar rats. According to these results, further studies are needed to elucidate the role of the renin-angiotensin system on alcohol use disorder pathophysiology. (c) 2021 Elsevier Inc. All rights reserved.Publication Metadata only Absans epilepsinin epileptogenez sürecinde nigro-striatal dopaminerjik yolağın rolünün araştırılması(2021-05-27) YANANLI, HASAN RACİ; GÜLHAN, REZZAN; GÜLÇEBİ İDRİZ OĞLU, MEDİNE; TOPLU A., YAVUZ M., ÇULPAN Y., TURGAN AŞIK Z. N., YANANLI H. R., GÜLHAN R., GÜLÇEBİ İDRİZ OĞLU M., ONAT F.Epilepsinin ve epileptogenezin patogenezinde rol alan nöronal mekanizmaların ortaya konması güncel hedeflerden bir tanesidir. Bu çalışmada non-konvülsif nöbetlerle karakterize absans epilepsisinin epileptogenez döneminde nigro-striatal dopaminerjik yolağın rolünün ortaya konması hedeflenmiştir. Bu amaçla Strasbourg kökenli genetik absans epilepsili sıçanların (GAERS) ve kontrol grubunu oluşturan Wistar sıçanların mediyal önbeyin demetine (MFB) 6-Hidroksidopamin (6-OHDA) verilmesi ile ortaya çıkan sonuçlar kıyaslanmıştır. Yöntemler: Deneylerde 30 günlük GAERS(n=5) ve Wistar sıçanlar(n=2) kullanıldı. Stereotaksik cerrahiyle 6-OHDA (8 µg/4µL/4dk hızında) MFB’ye (AP:-1,4; ML:1,6; V:7,1) enjekte edildi. Gruplarda 21 gün sonra adımlama, silindir ve rotasyon testleri yapıldı. Silindir testi için pleksiglas silindire alınan hayvanların sağ ve sol ön pençeleriyle silindire değme sayısı gözlendi. Adımlama testi için 50 cm parkurda tek ön pençesiyle ilerlemesi sağlanarak (diğer pençeler tutularak) adım sayısı hesaplandı. Rotasyon testi öncesi tüm hayvanlara apomorfin (0,05 mg/kg, subkutan) enjeksiyonu yapılarak 30 dakika boyunca hayvanların 3600 sola dönüşleri kaydedildi. Veriler ortalama±standart hata olarak belirtildi. Spearman korelasyon testi ile istatistiksel değerlendirme yapıldı. Bulgular: GAERS grubu için rotasyon sayısı 257,8±39,98; adımlama testinde adım sayısı sol 10±4,25, sağ 11,8±3,21 idi. Silindire değme testinde ön pençe değme sayısı sol 8,2±2,39, sağ 9,4±2,37 idi. Wistar grubu için rotasyon sayısı 245±89; adımlama testinde adım sayısı sol 0, sağ 5±4 idi. Silindire değme testinde ön pençe değme sayısı sol 7,5±1,5, sağ 11±3 idi. Gruplar arasında anlamlı bir korelasyon bulunmadı. Sonuçlar: 6-OHDA enjekte edilen sıçanların rotasyon testi ile adımlama ve silindir testleri arasında anlamlı bir korelasyon bulunamadı. Çalışmamızda grup sayılarının sınırlılığı nedeniyle, sayı arttırılarak çalışmanın devamı hedeflenmektedir. Çalışma TÜBİTAK (218S653) tarafından desteklenmektedir. Anahtar Kelimeler: GAERS, absans epilepsisi, rotasyon, adımlama, silindir testi Objective: One of the aims in the neuroscience is to define the neuronal mechanisms involved in the pathogenesis of epilepsy and epileptogenesis. In this study, we examined the role of the nigrostriatal dopaminergic pathway in the epileptogenesis of absence epilepsy characterized by non-convulsive seizures. We compared the findings of injection of 6-Hydroxydopamine (6-OHDA) to the medial forebrain bundle (MFB) of the Strasbourg genetic absence epilepsy rats (GAERS) with the control Wistar rats. Methods: The MFB (AP:-1.4; ML:1.6; V:7.1) of 30-days-old GAERS(n=5) and Wistar(n=2) animals were targeted and injected with 6-OHDA(8 µg/4µL/4min) by stereotaxic surgery. After 21 days, cylinder, stepping and rotation tests were performed. For the cylinder test, the number of right and left front paw touch to the plexiglass cylinder were counted separately from the animals which were observed for 20 min. For the stepping test, the number of steps taken was calculated by driving the animals on a single front paw (right and left front paws were calculated separately). Afterwards, all animals received an injection of apomorphine (0.05 mg/kg), and the rotation(3600) of animals were recorded for 30 min. Data were expressed as mean±standart error. Spearman correlation was performed. Results: In GAERS group, number of rotations were 257.8±40.0. In the stepping test, the left steps were 10±4.25; while the right were 11.8±3.21.In the cylinder test, the number of front paw touches with left paw were 8.2±2.39; and the right were 9.4±2.37. For the Wistar group, number of rotations were 245±89. In the stepping test, the left steps were 0; the right were 5±4. And the number of front paw touches left were 7.5±1.5; the right were 11±3 with no significant correlation between the groups. Conclusions: No significant correlation was found between rotation behavior and the stepping-cylinder test of animals. In the study, group numbers are planned to be increased. The study is supported by TUBITAK (218S653).Publication Metadata only The influence of dorsomedial hypothalamic nucleus on contralateral paraventricular nucleus in NMDA-mediated cardiovascular responses(2003) ONAT, FİLİZ; Gören, M. Zafer; Yananli, H. Raci; Berkman, Kemal; Onat, Filiz; Aker, RezzanDorsomedial (DMH) and paraventricular nuclei (PVN) are two important hypothalamic structures involved in the central regulation of cardiovascular regulation. L-Glutamic acid and gamma-aminobutyric acid (GABA) were demonstrated to elicit cardiovascular responses when administered via intracerebroventricular injection or parenchymal microinjections into the hypothalamic nuclei, participating in central cardiovascular regulation. In this study the interaction between the DMH and the PVN were investigated by means of microinjection and microdialysis techniques in Sprague-Dawley rats. Stereotaxic surgery was performed for the insertion of intracerebral parenchymal microinjection cannula into the right DMH and microdialysis probe into the left PVN. After a recovery period of 3 days, the iliac artery was cannulated for monitoring pulsatile blood pressure and heart rate by means of pressure transducer connected to a polygraph. Microinjection of 50 pmol NMDA into the DMH was performed and microdialysis perfusates were collected simultaneously from the PVN in the conscious rat model. L-Glutamic acid and GABA levels were analyzed by an isocratic HPLC method with the aid of a fluorescent detector. Microinjection of 50 pmol NMDA into the DMH produced significant increases in mean arterial pressure and heart rate. NMDA microinjection into the DMH produced a significant increase in L-glutamic acid release in the PVN, but no significant change in GABA release was observed. These results may indicate that stimulation of the DMH by NMDA results in subsequent stimulation of the PVN.