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    A different view on the pathophysiology of Parkinson's disease: a descendent neurochemical hypothesis?
    (Wolters Kluwer Medknow Publications, 2019) Yuluğ, Burak; Ozansoy, Mehmet; Çankaya, Şeyda
    [No abstract available]
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    A different view on the platelet aggregation inhibitor clopidogrel - a well-suitable anti-oedema agent in a preclinical model of brain injury?
    (Czech Medical Soc, 2019) Günal, Mehmet Yalçın; Yuluğ, Burak; Çağlayan, Berrak; Ozansoy, Mehmet; Kılıç, Ülkan; Keskin, İlknur; Kılıç, Ertuğrul
    Aim: The neuroprotective effects of clopidogrel have already been shown in various experimental models. Taking into account the fact that clopidogrel is well tolerated and approved for use in various clinical settings, it can be an attractive candidate for further clinical investigations, especially when the anti-oedema effect appears to be a reasonable adjuvant strategy, such as in brain injury (BI). Here we aimed to examine the neuroprotective role of clopidogrel in BI. Methods: To investigate the effects of clopidogrel, we induced BI in mice using a cold trauma model and evaluated the underlying cell survival/death mechanisms via cresyl violet, TUNEL staining and western blot analysis. Results: Clopidogrel at a dose of 3 mg/kg led to a significant reduction in brain swelling. Similar decreases were observed with 10 mg/kg and 30 mg/kg of clopidogrel. We also have shown that clopidogrel blocks the prominent inflammatory injury pathways and exerts a significant anti-apoptotic effect (3 and 30 mg/kg), which has boon associated with increased neuronal cell survival pathways. Clopidogrel (3, 10 and 30 mg/kg) dose-dependently altered the JNK, p-38, AKT, ERK and p53 levels. Conclusion: Our findings demonstrate that clopidogrel can be a novel candidate for the reduction of post-traumatic BI and oedema. We propose that it can be applied mainly in the acute phases of cerebral ischaemia, which is characterized by haemorrhagic transformation and brain oedema.
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    A rare entity of acquired idiopathic generalised anhidrosis which has been successfully treated with pulse steroid therapy: Does the histopathology predict the treatment response?
    (Ifjusagi Lap-es Konyvkiado Vallalat, 2020) Öktem, Ece Özdemir; Çankaya, Şeyda; Uykur, Abdullah Burak; Erdem, Nazan Şimşek; Yuluğ, Burak
    Acquired idiopathic generalised anhidrosis is an uncommon sweating disorder characterized by loss of sweating in the absence of any neurologic, metabolic or sweat gland abnormalities. Although some possible immunological and structural mechanisms have been proposed for this rare entity, the definitive pathophysiology is still unclear. Despite some successfully treated cases with systemic corticosteroid application, the dose and route of steroid application are controversial. Here, we present a 41-yearold man with lack of generalised sweating who has been successfully treated with high dose pulse intravenous prednisolone. We have discussed his clinical and histopathological findings as well as the treatment options in view of the current literature. © 2020 Ifjusagi Lap-es Konyvkiado Vallalat. All rights reserved.
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    Acute and post-acute neuromodulation induces stroke recovery by promoting survival signaling, neurogenesis, and pyramidal tract plasticity
    (Frontiers Media Sa, 2019) Çağlayan, Ahmet Burak; Beker, Mustafa Çağlar; Çağlayan, Berrak; Yalçın, Esra; Çağlayan, Aysun; Yuluğ, Burak; Kılıç, Ertuğrul
    Repetitive transcranial magnetic stimulation (rTMS) has gained interest as a non-invasive treatment for stroke based on the data promoting its effects on functional recovery. However, the exact action mechanisms by which the rTMS exert beneficial effects in cellular and molecular aspect are largely unknown. To elucidate the effects of high- and low-frequency rTMS in the acute-ischemic brain, we examined how rTMS influences injury development, cerebral blood flow (CBF), DNA fragmentation, neuronal survival, pro- and anti-apoptotic protein activations after 30 and 90 min of focal cerebral ischemia. In addition, inflammation, angiogenesis, growth factors and axonal outgrowth related gene expressions, were analyzed. Furthermore, we have investigated the effects of rTMS on post-acute ischemic brain, particularly on spontaneous locomotor activity, perilesional tissue remodeling, axonal sprouting of corticobulbar tracts, glial scar formation and cell proliferation, in which rTMS was applied starting 3 days after the stroke onset for 28 days. In the high-frequency rTMS received animals reduced DNA fragmentation, infarct volume and improved CBF were observed, which were associated with increased Bcl-xL activity and reduced Bax, caspase-1, and caspase-3 activations. Moreover, increased angiogenesis, growth factors; and reduced inflammation and axonal sprouting related gene expressions were observed. These results correlated with reduced microglial activation, neuronal degeneration, glial scar formation and improved functional recovery, tissue remodeling, contralesional pyramidal tract plasticity and neurogenesis in the subacute rTMS treated animals. Overall, we propose that high-frequency rTMS in stroke patients can be used to promote functional recovery by inducing the endogenous repair and recovery mechanisms of the brain.
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    Anterior cerebral artery infarcts; Two years follow-up study
    (Literatura Medica, 2018) Hanoğlu, Lütfü; Khanmammadov, Elmir; Demirci, Sema; Altın, Ummuhan; Kırbaş, Dursun; Hanoğlu, Taha; Yuluğ, Burak
    Objectives - Anterior cerebral infarct (ACA) infarcts are reported very rare that is due to the compensatory collateral circulation provided by the anterior communicating artery. There are very few studies reporting the long-term follow-up results of ACA infarcts regarding their aetiology, clinical features and prognosis. Most studies reported in the literature vary between several months to one year. Patients and methods - A total of 27 patients with ACA infarcts were registered (14 women and 13 men). The mean age of the patients was 68.5 (age range: 45-89 years). Results - Bilateral ACA infarcts were reported in four patients (14.8%), right ACA infarct in 11 (40%) patients and left ACA infarct in 12 patients (44%). During the initial examination 15 patients (55.5%) were found to have apathy, 13 patients (48%) had incontinence, nine patients (33.3%) had primitive reflexes, 11 patients (40.7%) had aphasia, while six patients (22.2%) were found to suffer from neglect. At the end of one-year follow-up, five patients (22.7%) were reported to have apathy, 6 patients (27.2%) had incontinence, one patient (4.5%) had primitive reflexes, while one patient (4.5%) was found to have permanent aphasia, and no patients was found to suffer from neglect. Conclusion - Here we present our clinical data regarding the aetiology, specific clinical characteristics (including the speech disorders) and prognosis of 27 patients with ACA infarcts during a relatively longer follow-up period (3 months - 30 months) in compared to previous literature. We show that there are differences in the etiological factors of ACA infarcts between the Asian and European communities. Regarding speech disorders which are frequently reported during ACA infarcts, our study results are in agreement with other studies suggesting that this clinical picture is more than a real aphasia and associated with general hypokinesia and reduction in psychomotor activity.
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    Beyond the therapeutic effect of rTMS in alzheimer's disease: A possible neuroprotective role of hippocampal BDNF?: A minireview
    (Bentham Science Publ Ltd, 2018) Yuluğ, Burak; Hanoğlu, Lütfü; Khanmammadov, Elmir; Düz, Özge Ariel; Polat, Burcu; Hanoğlu, Taha; Kılıç, Ertuğrul
    Repetitive transcranial magnetic stimulation (rTMS) is a well known non-invasive brain stimulation procedure which is capable of inducing the expression of the hippocampal BDNF that has been already shown to exert significant neuroprotective and pro-cognitive effects in AD. However, it is nearly impossible directly to evaluate the BDNF expression in humans after rTMS application. Here we summarized the underlying mechanisms of the neuroprotective and procognitive effect of BDNF that can be induced through a region-specific rTMS approach. Additionally, we have also evaluated the role of Magnetic Resonance Spectroscopy in monitoring the BDNF response after rTMS application in Alzheimer's Disease. We have provided strong evidence that rTMS exerts significant neuroprotective and pro-cognitive effects through the expression of hippocampal BDNF. Furthermore, Magnetic Resonance Spectroscopy might play a critical role in monitoring the BDNF response after rTMS application in AD patients. Such a sophisticated approach might be able to enlighten us on the time-dependent cognitive and neuroprotective correlates of the rtMS application in AD patients.
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    Cavernous sinus thrombosis due to mucor infection of ethmoid sinus
    (2024) Cankaya, Seyda; Çetin, Bahar Bakır; Oktem, Ece Ozdemir; Özşimşek, Ahmet; Lakadamyalı, Hatice; Yuluğ, Burak
    [Abstract Not Available]
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    Cinnamon polyphenol extract exerts neuroprotective activity in traumatic brain injury in male mice
    (Bentham Science Publ, 2018) Yuluğ, Burak; Kılıç, Ertuğrul; Altunay, Serdar; Ersavaş, Cenk; Orhan, Cemal; Dalay, Arman; Şahin, Kazım
    Introduction: Cinnamon polyphenol extract is a traditional spice commonly used in different areas of the world for the treatment of different disease conditions which are associated with inflammation and oxidative stress. Despite many preclinical studies showing the anti-oxidative and anti-inflammatory effects of cinnamon, the underlying mechanisms in signaling pathways via which cinnamon protects the brain after brain trauma remained largely unknown. However, there is still no preclinical study delineating the possible molecular mechanism of neuroprotective effects cinnamon polyphenol extract in Traumatic Brain Injury (TBI). The primary aim of the current study was to test the hypothesis that cinnamon polyphenol extract administration would improve the histopathological outcomes and exert neuroprotective activity through its antioxidative and anti-inflammatory properties following TBI. Methods: To investigate the effects of cinnamon, we induced brain injury using a cold trauma model in male mice that were treated with cinnamon polyphenol extract (10 mg/kg) or vehicle via intraperitoneal administration just after TBI. Mice were divided into two groups: TBI+vehicle group and TBI+ cinnamon polyphenol extract group. Brain samples were collected 24 h later for analysis. Results: We have shown that cinnamon polyphenol extract effectively reduced infarct and edema formation which were associated with significant alterations in inflammatory and oxidative parameters, including nuclear factor-KB, interleukin 1-beta, interleukin 6, nuclear factor erythroid 2-related factor 2, glial fibrillary acidic protein, neural cell adhesion molecule, malondialdehyde, superoxide dismutase, catalase and glutathione peroxidase. Conclusion: Our results identify an important neuroprotective role of cinnamon polyphenol extract in TBI which is mediated by its capability to suppress the inflammation and oxidative injury. Further, specially designed experimental studies to understand the molecular cross-talk between signaling pathways would provide valuable evidence for the therapeutic role of cinnamon in TBI and other TBI related conditions.
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    Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial
    (2023) Yuluğ, Burak; Altay, Özlem; Li, Xiangyu; Hanoğlu, Lütfü; Çankaya, Şeyda; Lam, Simon; Velioğlu, Halil Aziz; Yang, Hong; Coşkun, Ebru; İdil, Ezgi; Nogaylar, Rahim; Özşimşek, Ahmet; Bayram, Cemil; Bolat, İsmail; Öner, Sena; Tozlu, Özlem Özdemir; Arslan, Mehmet Enes; Hacımüftüoğlu, Ahmet; Yıldırım, Serkan; Arif, Muhammad; Shoaie, Saeed; Zhang, Cheng; Nielsen, Jens; Turkez, Hasan; Boren, Jan; Uhlen, Mathias; Mardinoğlu, Adil
    Abstract Background Alzheimer’s disease (AD) is associated with metabolic abnormalities linked to critical elements of neurodegeneration. We recently administered combined metabolic activators (CMA) to the AD rat model and observed that CMA improves the AD-associated histological parameters in the animals. CMA promotes mitochondrial fatty acid uptake from the cytosol, facilitates fatty acid oxidation in the mitochondria, and alleviates oxidative stress. Methods Here, we designed a randomised, double-blinded, placebo-controlled phase-II clinical trial and studied the efect of CMA administration on the global metabolism of AD patients. One-dose CMA included 12.35 g L-serine (61.75%), 1 g nicotinamide riboside (5%), 2.55 g N-acetyl-L-cysteine (12.75%), and 3.73 g L-carnitine tartrate (18.65%). AD patients received one dose of CMA or placebo daily during the frst 28 days and twice daily between day 28 and day 84. The primary endpoint was the diference in the cognitive function and daily living activity scores between the placebo and the treatment arms. The secondary aim of this study was to evaluate the safety and tolerability of CMA. A comprehensive plasma metabolome and proteome analysis was also performed to evaluate the efcacy of the CMA in AD patients. Results We showed a signifcant decrease of AD Assessment Scale-cognitive subscale (ADAS-Cog) score on day 84 vs day 0 (P=0.00001, 29% improvement) in the CMA group. Moreover, there was a signifcant decline (P=0.0073) in ADAS-Cog scores (improvement of cognitive functions) in the CMA compared to the placebo group in patients with higher ADAS-Cog scores. Improved cognitive functions in AD patients were supported by the relevant alterations in the hippocampal volumes and cortical thickness based on imaging analysis. Moreover, the plasma levels of
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    Comprehensive research on past and future therapeutic Strategies devoted to treatment of amyotrophic lateral sclerosis
    (2022) Sever, Belgin; Çiftçi, Halil İbrahim; Demirci,Hasan; Sever, Hilal; Ocak, Firdevs; Yuluğ, Burak; Tateishi, Hiroshi; Tateishi, Takahisa; Otsuka, Masami; Fujita, Mikako; Başak, Ayşe Nazlı
    Amyotrophic lateral sclerosis (ALS) is a rapidly debilitating fatal neurodegenerative disorder, causing muscle atrophy and weakness, which leads to paralysis and eventual death. ALS has a multifaceted nature affected by many pathological mechanisms, including oxidative stress (also via protein aggregation), mitochondrial dysfunction, glutamate-induced excitotoxicity, apoptosis, neuroinflammation, axonal degeneration, skeletal muscle deterioration and viruses. This complexity is a major obstacle in defeating ALS. At present, riluzole and edaravone are the only drugs that have passed clinical trials for the treatment of ALS, notwithstanding that they showed modest benefits in a limited population of ALS. A dextromethorphan hydrobromide and quinidine sulfate combination was also approved to treat pseudobulbar affect (PBA) in the course of ALS. Globally, there is a struggle to prevent or alleviate the symptoms of this neurodegenerative disease, including implementation of antisense oligonucleotides (ASOs), induced pluripotent stem cells (iPSCs), CRISPR-9/Cas technique, non-invasive brain stimulation (NIBS) or ALS-on-a-chip technology. Additionally, researchers have synthesized and screened new compounds to be effective in ALS beyond the drug repurposing strategy. Despite all these efforts, ALS treatment is largely limited to palliative care, and there is a strong need for new therapeutics to be developed. This review focuses on and discusses which therapeutic strategies have been followed so far and what can be done in the future for the treatment of ALS.
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    Differentiation of claustrum resting-state functional connectivity in healthy aging, Alzheimer's disease, and Parkinson's disease
    (2023) Ayyıldız, Sevilay; Velioğlu, Halil Aziz; Ayyıldız, Behçet; Sütçübaşı, Bernis; Hanoğlu, Lütfü; Bayraktaroğlu, Zübeyir; Yıldırım, Süleyman; Atasever, Alper; Yuluğ, Burak
    The claustrum is a sheet-like of telencephalic gray matter structure whose function is poorly understood. The claustrum is considered a multimodal computing network due to its reciprocal connections with almost all cortical areas as well as subcortical structures. Although the claustrum has been involved in several neurodegenerative diseases, specific changes in connections of the claustrum remain unclear in Alzheimer's disease (AD), and Parkinson's disease (PD). Resting-state fMRI and T1-weighted structural 3D images from healthy elderly (n = 15), AD (n = 16), and PD (n = 12) subjects were analyzed. Seed-based FC analysis was performed using CONN FC toolbox and T1-weighted images were analyzed with the Computational Anatomy Toolbox for voxel-based morphometry analysis. While we observed a decreased FC between the left claustrum and sensorimotor cortex, auditory association cortex, and cortical regions associated with social cognition in PD compared with the healthy control group (HC), no significant difference was found in alterations in the FC of both claustrum comparing the HC and AD groups. In the AD group, high FC of claustrum with regions of sensorimotor cortex and cortical regions related to cognitive control, including cingulate gyrus, supramarginal gyrus, and insular cortex were demonstrated. In addition, the structural results show significantly decreased volume in bilateral claustrum in AD and PD compared with HC. There were no significant differences in the claustrum volumes between PD and AD groups so the FC may offer more precise findings in distinguishing changes for claustrum in AD and PD. © 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.
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    DLPF Targeted Repetitive Transcranial Magnetic Stimulation Improves Brain Glucose Metabolism Along with the Clinical and Electrophysiological Parameters in CBD Patients
    (2022) Toprak, Güven; Hanoğlu, Lütfü; Çakır, Tansel; Gümtekin, Bahar; Velioğlu, Halil Aziz; Yuluğ, Burak
    Background: Corticobasal Degeneration (CBD) is a rare neurological disease caused by the pathological accumulation of tau protein. The primary pathological features of CBD include progressive neurodegenerative processes resulting in remarkable frontoparietal and basal ganglia atrophy. Objective: Like in many other neurodegenerative disorders, there is still no effective disease-modifying drug therapy in CBD. Therefore, the development of new treatment methods is of great importance. In this study, we aimed to assess the stimulating effects of high-frequency DLPFC rTMS on the motor, cognitive and behavioral disturbances in four CBD patients. Methods: Four (three females, one male) CBD patients who had been diagnosed as CBD were enrolled in this study. Patients were evaluated before and after the rTMS procedure regarding the motor, neuropsychometric and behavioral tests. The results of statistical analysis of behavioral and neuropsychometric evaluation were assessed via SPSS 18.0 package program. Data are expressed as mean, standard deviation. Before and after values of the groups were compared with the Wilcoxon sign rank test, and p<0.05 was considered significant. Results: We have provided strong preliminary evidence that the improvement in clinical parameters was associated with the normalizations of the theta activity and glucose metabolism. Conclusion: Our current results are consistent with some previous trials showing a strong association between DLPFC targeted rTMS and electrophysiological normalizations in the left DLPFC.
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    Emotional Burdens and Cognitive Decline: the Role of Anxiety in Mild Cognitive Impairment
    (Kafkas Üniversitesi, 2025) Sayman, Ceyhun; Aylak, Uğur; Çankaya, Şeyda; Yuluğ, Burak
    Aim: This study investigates the complex interactions between mild cognitive impairment (MCI), depression, and anxiety, focusing on how these factors affect cognitive function and progression risks. The goal is to inform early diagnostic strategies and targeted therapeutic interventions in individuals with MCI Matherial and Methods: This prospective study included 45 patients diagnosed with MCI (mean age: 66.1±7.7 years; 23 males [51%], 22 females [49%]) at a neurology outpatient clinic. Sociodemographic data, including education level and medical history, were collected. Cognitive and psychiatric assessments were conducted using the Montreal Cognitive Assessment (MoCA), Standardized Mini-Mental State Examination (SMMT), Hamilton Depression Rating Scale (HDRS), and Hamilton Anxiety Scale (HAS). Stratification was done according to anxiety severity, and comparisons were made across these groups on the cognitive performances. Results: Anxiety levels were significantly higher in females than males (p=0.001). While global MoCA and SMMT scores did not differ significantly by gender, males showed significantly better performance in verbal fluency (p=0.025) and a trend in abstract thinking (p=0.057). A significant decline in MoCA total scores was observed with increasing anxiety severity (p=0.024), with verbal fluency (p=0.011), abstract thinking (p=0.005), and attention (p=0.050) notably affected in the severe anxiety group. Conclusions: This study highlights anxiety as a key modifiable risk factor for cognitive impairment in MCI, with domain-specific deficits in executive function. Unlike depression, anxiety showed a stronger correlation with cognitive decline. These findings suggest that early identification and targeted treatment of anxiety in MCI could help delay progression to dementia and improve clinical outcomes.
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    FDG-PET scanning shows distributed changes in cortical activity associated with visual hallucinations in eye disease
    (Bentham Science Publ Ltd, 2019) Hanoğlu, Lütfü; Yıldız, Sultan; Çakır, Tansel; Hanoğlu, Taha; Yuluğ, Burak
    Background and Objective: Charles Bonnet Syndrome (CBS) has been defined as complex visual hallucinations (CVH) due to visual loss. The underlying mechanism of CBS is not clear and the underlying pathophysiology of the visual hallucinations in CBS patients and pure visually impaired patients is still not clear. Methods: In our study, we have scanned three patients with eye disease and CBS (VH+) and three patients with eye disease without CBS (VH-) using FDG-PET. Results: Our results showed underactivity in the pons and overactivity in primary right left visual cortex and inferior parietal cortex in VH- patients and underactivity in left Broca, left inf frontal primary visual cortex and anterior and posterior cingulate cortex in VH+ patients relative to the normative 18F-FDG PET data that was taken from the database consisting of 50 age-matched healthy adults without neuropsychiatric disorders. Conclusion: From this distributed pattern of activity changes, we conclude that the generation of visual hallucination in CBS is associated with bottom-up and top-down mechanism rather than the generally accepted visual deafferentation-related hyperexcitability theory.
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    Gerilim Tipi Baş Ağrısı Olan Bireylerde Temporomandibular Gevşetme Ve Miyofasial Gevşetme Tekniklerinin Yaşam Kalitesi, Depresyon Ve Baş Ağrısı Üzerine Etkisi
    (Yavuz YAKUT, 2024) Öz, Ayşe; Aracı, Ayça; Özşimşek, Ahmet; Taşkıran, Hanifegül; Yuluğ, Burak
    Amaç: Gerilim tipi baş ağrısı (GTBA) toplumda sıklıkla görülmektedir. Çalışmamızın amacı GTBA olan bireylerde temporomandibular eklem (TME) Yumuşak Doku Teknikleri (TME-YDT) ve miyofasial gevşetme (MFG) teknikliklerinin etkinliğini incelemektir. Yöntem: Uluslararası Baş Ağrısı Derneğinin Baş ağrısı sınıflandırması (ICHD-3)’na göre 18-65 yaşları arası GTBA tanısı alan 73 gönüllü birey dahil edildi. Bireyler randomizasyon metoduna göre Grup 1; TME-YDT, Grup 2; MFG Grubu ve Grup 3; Kontrol Grubu olmak üzere 3’e ayrıldı. Baş ağrısı, Headache Impact Test-6(HIT-6) ile; TMED Fonseca Ölçeği ile; Temporomandibular EHA cetvel yardımı ile; servikal EHA gonyometre ile; yaşam kalitesi, SF-36 Yaşam Kalite Ölçeği ile; depresyon, Beck Depresyon Ölçeği (BDÖ) ile; Anksiyete, Beck Anksiyete Ölçeği (BAÖ) ile değerlendirildi. Değerlendirmeler tedavi öncesi ve 4 haftalık tedavi sonunda yapıldı. Grup 1’e TME- YDT (anterior kaudal glide, masseter ve medial pterygoid kaslarına yumuşak doku mobilizasyonu), Temporal ve Suboksipital kaslara miyofasial gevşetme tekniği uygulandı. Grup 2’ye grup 1’e yapılan uygulamalara ek olarak Trapez, Rhomboid, Levator Scapula ve Sternocleidomasteideus kaslarına ve derin posterior servikal fasya gevşetme teknikleri uygulandı. Bulgular: Hem TME hem de MFG gruplarının FONSECA ve HIT6 total skorlarında meydana gelen değişimin kontrol grubuna göre anlamlı şekilde yüksek olduğu görüldü(p<0,05). Sonuç: GTBA tedavisinde TME yumuşak doku tekniklerinin miyofasial teknikler kadar etkili olduğu bulundu.
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    Ginkgo Biloba Özütünün in Vitro Alzheimer Hastalığı Modelinde TRPV1 Kanalları Aracılığıyla Koruyucu ve Terapötik Rolü
    (2023) Özşimşek, Ahmet; Övey, İshak Suat; Karacay, Ertan; Yuluğ, Burak
    Amaç: Ginkgo biloba’nın (GB) nöroblastom hücrelerinde mitokondriye bağımlı TRPV1 iyon kanalları üzerindeki etkisi Alzheimer hastalığı (AH) modeli oluşturularak araştırıldı. Yöntem: Bir AH modeli oluşturmak için SH-SY5Y hücrelerine okadaik asit uygulandı. Hücresel farklılaşmadan sonra yedi ana grupla organize edilen çalışma, GB’nin nöroblastom hücrelerinde AH’de kalsiyuma bağlı TRPV1 kanallarına etkisinin incelendiği in vitro çalışmadır. Bulgular: Kontrol grubu ile karşılaştırıldığında GB+AH, AH ve AH+GB gruplarında daha yüksek Ca 2+ konsantrasyonu saptandı (p<0,001). Ca 2+ düzeyi GB+AH ve AH+GB gruplarında AH grubuna göre daha düşüktü (p<0,001). Ayrıca GB+AH’de sitozolik Ca 2+ konsantrasyonu AH+GB grubuna göre daha düşüktü (p<0,05), apoptoz ve hücre içi reaktif oksijen türleri (ROS) değerleri GB+AH, AH ve AH+GB’de control grubuna göre daha yüksekti (p<0,001). Apoptoz ve hücre içi ROS değerleri AH grubunda GB+AH ve AH+GB grubuna göre daha yüksekti (p<0,001) ve AH+GB grubunda apoptoz düzeyi GB+AH grubuna göre daha yüksekti (p<0,001) ve mitokondriyal depolarizasyon, kaspaz 3 ve kaspaz 9 düzeyleri GB+AH, AH ve AH+GB gruplarında kontrol grubuna göre daha yüksekti (p<0,001). Ayrıca GB+AH+kapsazepin grubu, AH+kapsazepin grubu ve AH+GB+kapsazepin ile karşılaştırıldığında GB+AH grubu, AH grubu ve AH+GB gruplarında değerler daha düşüktü (p<0,001). Sonuç: Bu sonuçlar bize GB’nin TRPV1 kanalı üzerinden Alzheimer hastalığında tedavi edici etkisinin yanında koruyucu etkisinin olduğunu göstermektedir.
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    Investigation of the Antiepileptics on Levels of Vitamin D and Calcium
    (2022) Yuluğ, Burak; Özşimşek, Ahmet; Oktem, Ece Ozdemir
    Aim: We investigated the connection between D vitamin and factors such as the type of antiepileptic agent, patient age and gender.Methods: This retrospective case-control study enrolled a total of 301 participants, including 141 epilepsy patients with (n= 120) without drug (n=21) regimens followed up in Alanya Alaaddin Keykubat University neurology outpatient clinic and 160 healthy individuals who applied to the neurology outpatient clinic for different reasons from January 2018 to January 2021. Demographics, detailed history, use of medications, duration of antiepileptic use, plasma 25-hydroxy Vitamin D and calcium levels were determined.Results: The mean level of Vitamin D was 15.46 in the epilepsy group and 16.95 in the control group. Level of D Vitamine did not differ significantly by groups (p>0.05). There were no significant relationship regarding age and vitamin D levels in both groups while decreased Vitamin D levels were detected epileptic women. Vitamin D level was below 20 in 69.6% of healthy control group, 78.9% of carbamazepine users, 62.5% of lacosamide users, all lamotrigine users, 66.7% of levatiracetam users, and 72.4% of sodium valproate users. No significant connection were detected between levels of Vitamin D and the drug used (p>0.05) while a significant association was confirmed only between calcium levels and carbamazepine (p<0.05).Conclusion: Vitamin D and calcium levels can be found to be low in antiepileptic users; however, except for the calcium levels in the carbamazepine group, this decrease does not constitute a significant difference. 
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    Investigation of the Antiepileptics on Levels of Vitamin D and Calcium
    (2022) Yuluğ, Burak; Özşimşek, Ahmet
    Aim: We investigated the connection between D vitamin and factors such as the type of antiepileptic agent, patient age and gender. Methods: This retrospective case-control study enrolled a total of 301 participants, including 141 epilepsy patients with (n= 120) without drug (n=21) regimens followed up in Alanya Alaaddin Keykubat University neurology outpatient clinic and 160 healthy individuals who applied to the neurology outpatient clinic for different reasons from January 2018 to January 2021. Demographics, detailed history, use of medications, duration of antiepileptic use, plasma 25-hydroxy Vitamin D and calcium levels were determined. Results: The mean level of Vitamin D was 15.46 in the epilepsy group and 16.95 in the control group. Level of D Vitamine did not differ significantly by groups (p>0.05). There were no significant relationship regarding age and vitamin D levels in both groups while decreased Vitamin D levels were detected epileptic women. Vitamin D level was below 20 in 69.6% of healthy control group, 78.9% of carbamazepine users, 62.5% of lacosamide users, all lamotrigine users, 66.7% of levatiracetam users, and 72.4% of sodium valproate users. No significant connection were detected between levels of Vitamin D and the drug used (p>0.05) while a significant association was confirmed only between calcium levels and carbamazepine (p<0.05). Conclusion: Vitamin D and calcium levels can be found to be low in antiepileptic users; however, except for the calcium levels in the carbamazepine group, this decrease does not constitute a significant difference.
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    Melatonin affects the release of exosomes and tau-content in in vitro amyloid-beta toxicity model
    (Churchill Livingstone, 2020) Ozansoy, Mehmet; Ozansoy, Muzaffer Beyza; Yuluğ, Burak; Çankaya,Şeyda; Kılıç, Ertuğrul; Göktekin, Şule; Kılıç, Ülkan
    Background: Recent studies have been revealed that oxidative damage is the main cause of aging and age-related neurodegenerative diseases like Alzheimer's disease (AD). Melatonin is secreted from the pineal gland and its secretion has been found to be altered in AD. In the last decade the role of exosomes in spreading toxic proteins and inducing the propagation of diseases like AD has been discussed. However, it is not known how melatonin affects the amount of exosomes released from the cells and the content of the exosomes. Objective: Herein, we investigated the possible role of melatonin treatment in the releasing of exosomes and exosomal tau content in an in vitro A? toxicity model. Method: SH-SY5Y cell line was used. The optimum concentration of A? was determined by cell viability and cell proliferation tests. Melatonin (100 µM) was applied before and after A? application. Total exosomes isolated from cell culture media were immunoprecipitated. The amount of released exosomes and their tau content were analyzed by Western blots. Results: Our data demonstrated for the first time that melatonin treatment clearly affected the amount of released exosomes. It would decrease the amyloid beta load and toxicity by inhibiting exosome release. We also demonstated that melatonin also affected the level of tau carried by exosomes depending on whether melatonin was applied before or after A? application. Conclusion: It is considered that the effect of melatonin in the release of exosomes and exosomal tau content would contribute the development of therapeutic strategies in AD and related disorders. © 2019 Elsevier Ltd
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    Öğe
    Mezensefalik Kanamalı Hastalarda Fonksiyonel Sonuçlara Yönelik Prognostik Faktörler
    (2023) Oktem, Ece Ozdemir; Kumral, Emre; Çetin, Fatma Ece; Özşimşek, Ahmet; Dorukoğlu, Mehmet Mesut; Cankaya, Seyda; Yuluğ, Burak
    Amaç: Mezensefalik kanama (MH), spontan intraparankimal kanamanın nadir görülen bir prezentasyonudur. Bu çalışma, mezensefalik kanamalardaki prognostik parametreleri değerlendirmeyi amaçlamaktadır. Yöntem: Çalışmamızda; izole mezensefalik kanamalı olgular PRISMA (Sistematik İncelemeler ve Meta-Analizler için Tercih Edilen Raporlama Öğeleri) beyanına göre kapsamlı şekilde taranmıştır. Literatürde yer alan BT veya MRG ile kanıtlanmış 62 uygun vaka ve bunlara MRG ile doğrulanmış altı vaka olmak üzere 68 hasta çalışmaya dâhil edildi. Hastalar modifiye Rankin Skalasına göre (mRS), iyi sonlanım (0–2 puan) ve kötü sonlanım (3–6 puan) olarak iki gruba ayrılarak, prognostik parametreler istatistiksel olarak karşılaştırıldı. Bulgular: Çalışılan 68 hastanın 26’sının (%38) bilinci açık, 22’si (%32) letarjik, 20’si (%29) stupor veya koma ile başvurdu. İyi prognoz gösteren olguların 26’sında (%65), kötü prognoz gösterenlerin 12’sinde (%43) idiopatik kanama gözlendi (p=0,059). Tek değişkenli analizlerde, arteriyovenöz malformasyonlar (p=0,33) ve kavernomlar (p=0,19) prognoz ile ilişkili bulunmadı. Çoklu lojistik regresyon analizlerinde; hipertansiyon (OR, 51,22; CI%95, 1,92–1370,24; P=0,019, bilinç durumu (OR, 133,54; CI%95, 1,61–1113,3; p=0,03), başvuru anındaki NIHSS (OR, 57,23; CI%95, 2,87–1141,2; p=0,008) ve ventrodorsal kanama boyutu (?1 cm) (OR, 61,83; CI%95, 2,15–1779,2; p=0,016), kötü prognoz ile ilişkili bulundu. Mezensefalik kanamadan üç ay sonra, 40 hastanın (%59) klinik olarak iyi durumda, 28 (%41) hastanın klinik olarak kötü durumda olduğu, sekiz hastanın ise (%12) kaybedildiği gözlendi. Sonuç: Bu bulgular, hemorajinin ventrodorsal boyutunun ve inme başlangıcındaki klinik şiddetin mezensefalik kanama sonrası fonksiyonel sonuç açısından olası belirleyicileri olduğunu göstermektedir.