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Öğe FGF-18 alleviates memory impairments and neuropathological changes in a rat model of Alzheimer’s disease(Temmuz 2023) Çiltaş, Arzuhan Yeşildağ; Karabulut Sebahattin; Şahin, Bilal; Filiz, Ahmet Kemal; Yulak, Fatih; Özkaraca, Mustafa; Karatas, Özhan; Çetin, AliAlzheimer’s disease (AD) is a multifactorial pathology marked by amyloid beta (Aβ) accumulation, tau hyper phosphorylation, and progressive cognitive decline. Previous studies show that fibroblast growth factor 18 (FGF18) exerts a neuroprotective effect in experimental models of neurodegeneration; however, how it affects AD pathology remains unknown. This study aimed to ascertain the impact of FGF18 on the behavioral and neuropathological changes in the rat model of sporadic AD induced by intracerebroventricular (ICV) injection of streptozotocin (STZ). The rats were treated with FGF18 (0.94 and 1.88 pmol, ICV) on the 15th day after STZ injection. Their cognitive function was assessed in the Morris water maze and passive avoidance tests for 5 days from the 16th to the 21st days. Aβ levels and histological signs of neurotoxicity were detected using the enzyme linked immunosorbent assay (ELISA) assay and histopathological analysis of the brain, respectively. FGF18 mildly ameliorated the STZ-induced cognitive impairment; the Aβ accumulation was reduced; and the neuronal damage including pyknosis and apoptosis was alleviated in the rat brain. This study highlights the promising therapeutic potential for FGF18 in managing AD.Öğe Investigation of anti-epileptic mechanisms of 5HT1A receptor with pentylenetetrazole induced epilepsy model in rats(Sivas Cumhuriyet University, 2019) Şahin, Bilal; Özdemir, Ercan; Taşkıran, Ahmet Şevki; Gümüş, Erkan; Ergül, MustafaObjective: According to current neurophysiological evidence, the role of 5-hydroxytryptamine (5-HT) receptors in epileptic seizure formation is still not fully elucidated. The aim of this study was to investigate the effects of 5-HT1A receptor on epileptic seizure with pentylenetetrazole induced epilepsy in rats. Method: In this study, 28 male Wistar Albino rats weighing 240-260 g were used. Pentylenetetrazole (PTZ, 35 mg/kg, i.p.) was injected to the rats to induce epilepsy and seizure stages were determined according to the Racine scale. Electrodes were placed in the skulls of the animals under stereotaxis for ECoG recording. All the experimental animals were sacrificed by decapitation after ECoG and video recordings. GABA level was measured using the Elisa kit from brain tissues, and c-Fos expression was shown immunohistochemically. Results: According to the results, it was shown that 8-OH-DPAT increased the time of initial myoclonic jerk (FMJ (p<0.05). However, the number of epileptic spikes was reduced by 8-OH-DPAT (p<0.05). GABA levels decreased in PTZ group (p<0.05). 8-OH-DPAT and WAY-100135 decreased c-Fos expression in all hippocampal areas (p<0.05). Conclusions: In conclusion, 5-HT1A receptor agonist 8-OH-DPAT, showed an anti-epileptic effect. The anti-epileptic effects of 5-HT1A receptor were found to be inconsistent with changes in GABA level. c-Fos expression is a marker of neuronal activation and may be related to the anti-convulsive effect of 5-HT1A receptor.Öğe Investigation of the Effect of Diazepam on Nitric Oxide Synthase and Brain-Derived Neurotrophic Factor in Pentylenetetrazole-Induced Acute Seizure Model(Bingöl Üniversitesi, 2022) Şahin, Bilal; Güneş, HandanThe aim of this study was to investigate the effect of diazepam on nitric oxide synthase (NOS) and brain-derived neurotrophic factor (BDNF) in the anti-convulsant activity of diazepam on pentylenetetrazole (PTZ) induced seizures in rats. 24 male Wistar Albino rats were used in the study. Rats were divided into 4 groups as control group, saline (1 mL kg-1) +PTZ, diazepam (0.5 mg kg-1) +PTZ and diazepam (2 mg kg-1) +PTZ group (n=6). For biochemical studies, 24 hours after PTZ application, brain tissues of all rats were removed and cortex and hippocampus regions were isolated NOS and BDNF levels in the cortex and hippocampus were measured using ELISA kits. Diazepam significantly decreased the seizure stage and prolonged the first myoclonic jerk (IMJ) time compared to the saline group (p<0.001). Saline+PTZ significantly decreased NOS levels in the hippocampus when compared to the control group (p<0.05). However, the diazepam+PTZ groups significantly increased the hippocampal NOS level compared to the saline+PTZ group (p<0.001). In addition, the saline + PTZ group increased the BDNF level in the cortex and hippocampus compared to the control (p<0.05), while the BDNF level was lower in the diazepam+PTZ group compared to the saline+PTZ group (p<0.001). Diazepam increased NOS levels in the hippocampus and decreased BDNF levels in the cortex and hippocampus. In conclusion, the regulatory effect of diazepam on NOS and BDNF may be related to its anti-convulsant mechanisms.Öğe Investigation of the Effect of Folic Acid on Ethosuximide in Pentylenetetrazole-Induced Acute Seizures in Mice(Kırşehir Ahi Evran Üniversitesi, 2022) Çiltaş, Arzuhan Çetindağ; Şahin, BilalPurpose: Epilepsy is one of the most prevalent neurological diseases today. Despite various treatments, there is still no complete seizure control. Studies have shown the positive effects of folic acid (FA) and its derivatives on seizures. The objective of this study is to investigate Caspase-3 and TOS activity in brain tissues as well as the effect of folic acid on ethosuximide (ETX) in mice with pentylenetetrazol-induced seizures.Materials and Methods: In this study, 30 mice of BALB/c species were divided randomly into 5 groups: Control; pen-tylenetetrazol (PTZ); PTZ-induced seizure group; FA in which 3 mg/kg FA and PTZ were administered for 7 days; ETX in which 50 mg/kg ETX and PTZ were administered for 7 days; FA+ ETX in which 3 mg/kg FA and 50 mg/kg ETX and PTZ were administered for 7 days. The brain tissues of all mice were dissected, then the cortex and hippocampus were separated 24 hours after PTZ application.Results: FA, ETX and FA+ETX groups significantly decreased the seizure stage compared to the PTZ group, and similarly prolonged the first myoclonic jerk times, but the FA and FA+ETX groups were found to decrease the onset of generalizedtonic–clonic seizures (p<0.05). However, the FA and FA+ETX groups decreased the hippocampal TOS levels. (p<0.05). Similarly, hippocampal caspase-3 levels were lower in the FA group (p<0.05).Conclusion: FA can be a useful therapeutic agent for the treatment of epilepsy with its antioxidant and antiapoptotic properties. The synergistic effect of FA with ETX can promote its protective effect against neuronal damageÖğe Sugammadex Causes C6 Glial Cell Death and Exacerbates Hydrogen Peroxide-Induced Oxidative Stress(Sivas Cumhuriyet University, 2022) Şahin, Bilal; Karabulut, SabahattinObjective: Sugammadex (SUG) quickly reverses steroidal neuromuscular blocking drugs after anesthesia. It has been reported that SUG has a toxic effect on neurons in primary culture. This study aims to examine the effect of SUG on glial cell viability, oxidative stress, and apoptosis in C6 glial cells after exposure to H2O2.Method: In this study, C6 glioma cell line was used to study the effect of SUG on the glial cell in four cell groups. The control group was untreated. Cells in the H2O2group were treated with 0.5 mM H2O2 for 24 h. Cells in the SUG group were treated with 50 μg/mL SUG for 24 h. Cells in the SUG+ H2O2 group were pre-treated with 50 μg/mL of SUG for 1 h before 24-h exposure to 0.5 mM H2O2. Cell viability was evaluated using XTT assay. Total antioxidant status (TAS), total oxidant status (TOS), caspase-3, Bax, 8-hydroxy-2′ -deoxyguanosine (8-OHdG), and cleaved-PARP levels in the cells were measured by commercial kits. Results: SUG significantly decreased the viability of C6 cells after H2O2-induced oxidative stress (p < 0.05). SUG pretreatment also raised TOS levels and led to increased Bax, Caspase-3, 8-OHdG, and cleaved PARP levels after H2O2-induced oxidative damage in C6 cells (p < 0.05).Öğe Sıçanlarda pentilentetrazol ile oluşturulan epilepsi modelinde serotonin reseptörlerin anti-epileptik etki mekanizmalarının araştırılması(Sivas Cumhuriyet Üniversitesi, 2019) Şahin, Bilal; Özdemir, ErcanGüncel nörofizyolojik kanıtlara göre, epileptik nöbet oluşumunda 5-hidroksitriptamin (5-HT) reseptörlerin rolü hala tam olarak aydınlatılmış değildir. Bu araştırmada amacımız, pentilentetrazol (PTZ) ile epilepsi oluşturulmuş sıçanlarda 5-HT1, 5-HT3 ve 5-HT7 reseptörlerin epileptik nöbet üzerine etkilerini araştırmaktı. Çalışmada 56 adet 240-260 g ağırlığında erkek Wistar Albino sıçan kullanıldı. Epilepsi oluşturmak için sıçanlara pentilentetrazol (PTZ, 35 mg/kg, i.p.) enjekte edildi ve nöbet evreleri Racine skalasına göre belirlendi. Elektrokortigram (ECoG) kaydı için hayvanların kafataslarına sterotaksi altında elektrotlar yerleştirildi. EcoG ve video kayıtları alındıktan sonra tüm deney hayvanları dekapitasyon ile sakrifiye edildi. Beyin dokularından GABA düzeyi Elisa kit ile ölçüldü ve c-Fos ekspresyonu immünohistokimyasal olarak gösterildi. Bulgular 8-OH-DPAT'ın ilk myoklonik jerk (İMJ) başlama zamanını arttırdığını, klozipinin ise azalttığını gösterdi (p<0,05). Epileptik spike sayısını 8-OH-DPAT, SR-57227 ve SB-266970 azaltırken klozapin ise arttırdı (p<0,05). GABA seviyeleri PTZ ve klozapin grubunda azalma gösterdi (p<0,05). Aksine SB-266970 grubunda düzeyi arttı (p<0,05). 8-OH-DPAT ve WAY-100135 c-Fos ekspresyonunu hipokampüsün tüm alanlarında azalttı (p<0,05). Buna karşın, klozapin dentat girus (DG) ve CA3 alanlarında c-Fos ekspresyonunu arttırdı (p<0,05). 5-karboksitriptamin tüm hipokampal alanlarda c-Fos ekspresyonunu azaltırken SB-266970, DG ve CA3 alanlarında c-Fos ekspresyonunu arttırdı (p<0,05). Sonuç olarak, 5-HT1 ve 5-HT3 reseptör agonistleri anti-epileptik etki, 5-HT7 reseptör agonistleri ise pro-konvülzan etki göstermiştir. 5-HT3 ve 5-HT7 reseptörlerin anti-epileptik etkileri GABA düzeyi değişiklikleri ile uyumlu bulunmuştur. Nöronal aktivasyon belirteci olan c-Fos ekspresyon sonuçları, 5-HT1 ve 5-HT3 reseptörlerinin anti-konvülzif etkisi ile ilişkili olabileceğini göstermektedir.Öğe The Role of Captopril on Pentylenetetrazole-Induced Seizures in Rats(Ümit Muhammet KOÇYİĞİT, 2023) Çiltaş, Arzuhan Çetindağ; Şahin, BilalABSTRACT: Purpose: In recent years, experimental studies have shown that some angiotensin-converting enzyme (ACE) inhibitors with antihypertensive effects have anticonvulsant effects against seizures. After the seizure, the process of inflammation begins in the brain and body, with the production of free radicals. Renin has some effects on the central nervous system of the angiotensin system. The current study's objective was to examine how captopril, an ACE inhibitor, affects neuroinflammation in the hippocampus and cortical areas in acute epileptic seizures and post-seizures induced by pentylenetetrazole (PTZ). Material and Methods: Eighteen Wistar Albino rats were separated into three groups: control, PTZ (serum physiologic 1 ml/kg as solvent), and captopril (50 mg/kg/day for 7days). To produce epileptic seizures, PTZ (45 mg/kg) was delivered thirty minutes after the drug was administered. The animals were monitored during 30 minutes to record seizures scoring scale and the onset time of first myoclonic jerk (FMJ). In the brain tissue, the activity of TNF- α, IL-1 β, NF-kB, COX-1, and COX-2 were examined. Results: Captopril increased FMJ onset time and reduced seizure stage as compared to the PTZ group (p
