Researcher: Özkan, Esra
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Özkan, Esra
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Publication Metadata only MTBR-243 in the early diagnoses of AD and the role of microglia/carbenoxolone as localized therapeutic interventions in AD rats(Wiley, 2022) Anwar, Mai M.; N/A; Özkan, Esra; Özdemir, Yasemin Gürsoy; Researcher; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); N/A; N/A; School of Medicine; N/A; 170592N/APublication Metadata only Assessing the role of primary healthy microglia and gap junction blocker in hindering Alzheimer’s disease neuroinflammatory type: early approaches for therapeutic intervention(Frontiers Media S.A., 2023) Anwar, Mai M.; N/A; Özdemir, Yasemin Gürsoy; Özkan, Esra; Shomalizadeh, Narges; Kesibi, Judy; Özler, Ceyda; Faculty Member; Researcher; PhD Student; Master Student; PhD Student; Master Student; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; N/A; Graduate School of Health Sciences; Graduate School of Health Sciences; Graduate School of Health Sciences; Graduate School of Health Sciences; 170592; N/A; N/A; N/A; N/A; N/AAlzheimer’s disease (AD) is a predominantly heterogeneous disease with a highly complex pathobiology. The presence of amyloid-beta (Aβ) depositions and the accumulation of hyperphosphorylated tau protein remain the characteristic hallmarks of AD. These hallmarks can be detected throughout the brain and other regions, including cerebrospinal fluid (CSF) and the spinal cord. Microglia cells, the brain-resident macrophage type of the brain, are implicated in maintaining healthy brain homeostasis. The localized administration of primary healthy microglia (PHM) is suggested to play a role in mitigating AD hallmark depositions and associated cognitive dysfunction. Carbenoxolone (CBX) is the most common gap junction blocker. It cannot effectively cross the blood–brain barrier (BBB) under systemic administration. Therefore, localized administration of CBX may be a recommended intervention against AD by acting as an antioxidant and anti-inflammatory agent. This study aims to determine whether the localized intracerebroventricular (ICV) administration of PHM and CBX may act as an effective therapeutic intervention for AD neuroinflammatory type. In addition, this study also aims to reveal whether detecting AD hallmarks in the spinal cord and CSF can be considered functional and effective during AD early diagnosis. Male albino rats were divided into four groups: control (group 1), lipopolysaccharide (LPS)-induced AD neuroinflammatory type (group 2), ICV injection of LPS + isolated PHM (group 3), and ICV injection of LPS + CBX (group 4). Morris water maze (MWM) was conducted to evaluate spatial working memory. The brain and spinal cord were isolated from each rat with the collection of CSF. Our findings demonstrate that the localized administration of PHM and CBX can act as promising therapeutic approaches against AD. Additionally, Aβ and tau toxic aggregates were detected in the spinal cord and the CSF of the induced AD model concomitant with the brain tissues. Overall, it is suggested that the ICV administration of PHM and CBX can restore normal brain functions and alleviate AD hallmark depositions. Detecting these depositions in the spinal cord and CSF may be considered in AD early diagnosis. As such, conducting clinical research is recommended to reveal the benefits of related therapeutic approaches compared with preclinical findings.Publication Metadata only Investigation of factors affecting the side of the disease onset in Parkinson's disease(Turkish Neuropsychiatry Assoc-Turk Noropsikiyatri Dernegi, 2022) Selte, Ceren Muserref; N/A; Özkan, Esra; Çakmak, Özgür Öztop; Şekerdağ, Emine; Ertan, Fatoş Sibel; Researcher; Faculty Member; Researcher; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); N/A; School of Medicine; School of Medicine; N/A; School of Medicine; N/A; 299358; N/A; 112829Introduction: Parkinson's disease (PD) is a progressive neurodegenerative disease that starts unilaterally in almost all cases and tends to emerge on the side of the dominant hand, but what we know about the cause of this lateralization is limited. Frequent use of the extremity and physical activity are argued to be protective from PD in preclinical and clinical studies. This study aimed to evaluate the effect of handedness and working in occupations that require continuous use of upper extremities on the disease onset-side.Methods: We retrospectively collected 84 PD patients who applied to Koc University Neurology outpatient clinic between July 2016-October 2018. We analyzed the parameters of the side and region of disease onset, age of onset, number of drugs used for PD, hand preference, and patients' occupations.Results: The median age of our study group was 61 (53-69). Thirty (36%) of the 84 patients were women. Seventy-nine patients (94%) were right-handed. Eighty-three (99%) had asymmetric onset. The disease started on the dominant hand side in 47 patients (57%) and on the non dominant hand side in 36 (43%) patients. In our group with a median disease duration of four (2-7) years, the side with more severe complaints measured with the Unified Parkinson's Disease Evaluation Scale was consistent with the onset-side of the disease (p<0.001). In addition, the number of drugs used for PD and the scale score were higher in patients with longer disease duration (p=0.039, p=0.005). The number of drugs used for PD was also higher in patients with lower extremity-onset or both upper and lower extremities affected simultaneously than the upper extremity-onset (p=0.005). While the probability of starting on the dominant side was 43% in patients working in occupations requiring continuous use of upper extremities, it was 65% in others (p=0.027).Conclusion: According to this study, the onset of PD tends to be on the dominant hand side. Continuous upper extremity use may reduce the possibility of starting on the dominant side.Publication Metadata only Determinants of high circulating myeloperoxidase and matrix metalloproteinase-9 levels in coronary artery disease patients with obstructive sleep apnea: a secondary analysis of the RICCADSA study(Elsevier, 2022) N/A; N/A; Peker, Yüksel; Özkan, Esra; Çelik, Yeliz; Faculty Member; Researcher; Researcher; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; Graduate School of Social Sciences and Humanities; Graduate School of Health Sciences; 11480; N/A; N/AN/APublication Metadata only Investigation of factors affecting spontaneous blink frequency in Parkinson's disease(Celal Bayar Üniversitesi, 2022) Şelte, Ceren Müşerref; N/A; Özkan, Esra; Çakmak, Özgür Öztop; Şekerdağ, Emine; Özdemir, Yasemin Gürsoy; Researcher; Faculty Member; Researcher; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; School of Medicine; N/A; School of Medicine; N/A; 299358; N/A; 170592Objective: Parkinson's disease (PD) is a neurodegenerative movement disorder with dopaminergic loss in the brain. Frequency of spontaneous eye blink (FSEB) is also known to be a marker that provides information about the brain's dopamine sources. In this context, we designed this study to reveal the frequency of spontaneous eye blink in Parkinson's patients from Turkey and to investigate the factors affecting this frequency. and also, we would like to show the power of FSEB in the differential diagnosis of PD clinical subtypes. Materials and Methods: For our study, 168 patients who applied Koc University Neurology Department between 2016 July and 2021 July and had at least one-minute examination video were retrospectively scanned. One hundred nineteen patients diagnosed with PD from their files were included in the study. Analyzes were performed for the relationship between the patients' number of spontaneous eye blinks in 1 minute and the follow-up information. Results: The median age of the patients participating in our study was 60 (52-69) years. Forty-one (35%) were women. The frequency of spontaneous eye blink of our group was measured as 12 (6-25)/min. In regression analysis for blink frequency, age was found to be the predictor when evaluated together with sex, disease duration, clinical subtype, and l-dopa equivalent dose (P=0.021). Conclusion: As a result, the frequency of spontaneous eye blink decreases with age. The frequency of spontaneous blink in patients with Parkinson's disease is associated with age, regardless of gender, disease duration, disease clinical subtype, and the l-dopa equivalent dose of dopaminergic drugs used. Therefore, FSEB cannot be used as a potent biomarker for categorization in the PD population. / Giriş ve Amaç: Parkinson hastalığı (PH) beyinde dopaminerjik kayıpla giden nörodejeneratif bir hareket bozukluğudur. Spontan göz kırpma sıklığı (SGKS) da beynin dopamin kaynakları hakkında bilgi veren bir belirteç olduğu bilinmektedir. Bu bağlamda, Türkiye’deki Parkinson hastalarında spontan göz kırpma sıklığının ortaya konması, bu sıklığa etki eden faktörlerin araştırılması ve bir biyoelirteç olarak klinik PH alt tiplerini belirlemede SGKS’nin değerinin belirlenmesi için bu çalışmayı tasarladık. Gereç ve Yöntemler: Çalışmamız için Temmuz 2016-Temmuz 2021 tarihleri arasında Koç Üniversitesi Nöroloji Bölümüne başvuran ve en az bir dakikalık muayene videosu mevcut olan 168 hasta retrospektif olarak taranmıştır. Dosyalarından PH teşhisi olan 119 hasta çalışmaya dahil edilmiştir. Hastaların 1 dakikadaki göz kırpma sayıları ile takip bilgileri arasındaki ilişki için analizler gerçekleştirilmiştir. Bulgular: Çalışmamıza katılan hastaların medyan yaşı 60 (52-69) olarak saptanmıştır. Katılımcılardan 41 tanesi (%35) kadındır. Grubumuzun spontan göz kırpma sıklığı 12 (6-25)/dk olarak ölçülmüştür. Göz kırpma sıklığı ikili lojistik regresyon analizlerinde, cinsiyet, hastalık süresi, hastalık klinik tipi ve l-dopa eşdeğer dozu ile beraber değerlendirildiğinde yaşla ilişkili bulunmuştur (p=0,021). Sonuç: Sonuç olarak SGKS yaşla beraber düşüş göstermektedir. Parkinson hastalarında spontan göz kırpma sıklığı, cinsiyet, hastalık süresi, hastalık klinik tipi ve kullanılan dopaminerjik ilaçların l-dopa eşdeğer dozundan bağımsız olarak hastanın yaşı ile ilişkilidir. Bu nedenle SGKS, Parkinson hastalığı popülasyonunda kategorizasyon için güçlü bir biyobelirteç olarak kullanılamaz.Publication Metadata only Occipital bending in migraine with visual aura(Wiley, 2021) N/A; N/A; Özkan, Esra; Özdemir, Yasemin Gürsoy; Researcher; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); N/A; School of Medicine; N/A; 170592Objective To analyze occipital bending (OB) frequency in patients with migraine with visual aura compared with those without aura. Background A unique type of asymmetry in the human brain in which one occipital pole crosses the midline and bends over the other pole is called OB. OB frequency has been shown to be related to major psychiatric diseases. Hence, it may suggest more than an anatomical variation. Structural differences in the brain have been demonstrated but unequivocally between patients with migraine with aura and without aura. OB is newly recognized, and we aimed to evaluate its frequency among patients with migraine. Methods For this retrospective cohort study, we reviewed our records from 2016 to 2021 from a database of the outpatient headache clinic of Koc University Hospital. Results We found 84 patients with migraine who fulfilled diagnostic criteria for migraine with aura and migraine without aura and also had cranial magnetic resonance imaging. The median age of the population was 40 (IQR, 32-52). The female-to-male ratio of participants was 2:1. A quarter of the patients had visual aura. The prevalence of OB in patients with migraine in our retrospective study was 33.3% (28/84). Between our study groups, OB was significantly higher in patients with migraine with visual aura (57.1%, 12 out of 21 patients) than in those without aura (25.4%, 16 out of 63), (odds ratio 3.9 (95% confidence interval 1.4 to 11.0), p = 0.015). Conclusion OB frequency is two times higher in patients with migraine with visual aura. It may have pathophysiological implications.Publication Metadata only The role of Extracellular Matrix alterations in mediating Astrocytes damage, and Pericytes dysfunction in Alzheimer's disease: a comprehensive review(Wiley, 2022) N/A; N/A; N/A; Anwar, Mai; Özkan, Esra; Özdemir, Yasemin Gürsoy; Other; Researcher; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); N/A; N/A; School of Medicine; N/A; N/A; 170592The brain is a highly vascularized tissue protected by the blood-brain barrier (BBB), a complex structure allowing only necessary substances to pass through into the brain while limiting the entrance of harmful toxins. The BBB comprises several components, and the most prominent features are tight junctions between endothelial cells (ECs), which are further wrapped in a layer of pericytes. Pericytes are multitasked cells embedded in a thick basement membrane (BM) that consists of a fibrous extracellular matrix (ECM) and are surrounded by astrocytic endfeet. The primary function of astrocytes and pericytes is to provide essential blood supply and vital nutrients to the brain. In Alzheimer's disease (AD), long-term neuroinflammatory cascades associated with infiltration of harmful neurotoxic proteins may lead to BBB dysfunction and altered ECM components resulting in brain homeostatic imbalance, synaptic damage, and declined cognitive functions. Moreover, BBB structure and functional integrity may be lost due to induced ECM alterations, astrocyte damage, and pericytes dysfunction, leading to amyloid-beta (A beta) hallmarks deposition in different brain regions. Herein, we highlight how BBB, ECM, astrocytes, and pericytes dysfunction can play a leading role in AD's pathogenesis and discuss their impact on brain functions.Publication Metadata only Blood-brain barrier leakage and perivascular collagen accumulation precede microvessel rarefaction and memory impairment in a chronic hypertension animal model(Springer/Plenum Publishers, 2021) N/A; Özkan, Esra; Taş, Yağmur Çetin; Şekerdağ, Emine; Kızılırmak, Ali Burak; Taş, Ali; Yıldız, Erdost; Eser, Hale Yapıcı; Karahüseyinoğlu, Serçin; Zeybel, Müjdat; Özdemir, Yasemin Gürsoy; Researcher; Researcher; Researcher; Master Student; Researcher; PhD Student; Faculty Member; Faculty Member; Faculty Member; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); N/A; School of Medicine; N/A; Graduate School of Health Sciences; N/A; Graduate School of Health Sciences; School of Medicine; School of Medicine; School of Medicine; School of Medicine; N/A; N/A; N/A; N/A; N/A; 134359; 110772; 214694; 170592Hypertension (HT) is one of the main causes of vascular dementia, lead to cognitive decline. Here, we investigated the relationship between cerebral microvessels, pericytes, extracellular matrix (ECM) accumulation, blood-brain barrier (BBB) breakdown, and memory impairment at mid-life in a chronic hypertension animal model. Spontaneously hypertensive rats (SHRs) (n = 20) are chosen for the model and age matched Wistar rats (n = 16) as controls. Changes in brain microvasculature and in vitro experiments are shown with immunofluorescence studies and cognition with open field, novel object recognition, and Y maze tests. There was a significant reduction in pericyte coverage in SHRs (p = 0.021), while the quantitative parameters of the cerebral microvascular network were not different between groups. on the other hand, parenchymal albumin leakage, as a Blood-brain barrier (BBB) breakdown marker, was prominent in SHRs (p = 0.023). Extracellular matrix (ECM) components, collagen type 1, 3 and 4 were significantly increased (accumulated) around microvasculature in SHRs (p = 0.011, p = 0.013, p = 0.037, respectively). Furthermore, in vitro experiments demonstrated that human brain vascular pericytes but not astrocytes and endothelial cells secreted type I collagen upon TGF beta 1 exposure pointing out a possible role of pericytes in increased collagen accumulation around cerebral microvasculature due to HT. Furthermore, valsartan treatment decreased the amount of collagen type 1 secreted by pericytes after TGF beta 1 exposure. At the time of evaluation, SHRs did not demonstrate cognitive decline and memory impairments. Our results showed that chronic HT causes ECM accumulation and BBB leakage before leading to memory impairments and therefore, pericytes could be a novel target for preventing vascular dementia.Publication Metadata only Hyperglycemia with or without insulin resistance triggers different structural changes in brain microcirculation and perivascular matrix(Springer/Plenum Publishers, 2023) Pekmez, Murat; N/A; Özkan, Esra; Taş, Yağmur Çetin; Şekerdağ, Emine; Yiğit Alpdoğan, Buket; Shomalizadeh, Narges; Özler, Ceyda; Kesibi, Judy; Kızılırmak, Ali Burak; Eser, Hale Yapıcı; Zeybel, Müjdat; Karahüseyinoğlu, Serçin; Özdemir, Yasemin Gürsoy; Researcher; Researcher; Researcher; Researcher; PhD Student; PhD Student; Master Student; Master Student; Master Student; Faculty Member; Faculty Member; Faculty Member; Faculty Member; N/A; School of Medicine; Graduate School of Health Sciences; N/A; Graduate School of Health Science; Graduate School of Health Science; Graduate School of Health Sciences; Graduate School of Health Sciences; Graduate School of Health Sciences; School of Medicine; School of Medicine; School of Medicine; School of Medicine; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; 134359; 214694; 110772; 170592Both type-1 and type-2 DM are related to an increased risk of cognitive impairment, neurovascular complications, and dementia. The primary triggers for complications are hyperglycemia and concomitant insulin resistance in type-2 DM. However, the diverse mechanisms in the pathogenesis of diabetes-related neurovascular complications and extracellular matrix (ECM) remodeling in type-1 and 2 have not been elucidated yet. Here, we investigated the high fat-high sucrose (HFHS) feeding model and streptozotocin-induced type-1 DM model to study the early effects of hyperglycemia with or without insulin resistance to demonstrate the brain microcirculatory changes, perivascular ECM alterations in histological sections and 3D-reconstructed cleared brain tissues. One of the main findings of this study was robust rarefaction in brain microvessels in both models. Interestingly, the HFHS model leads to widespread non-functional angiogenesis, but the type-1 DM model predominantly in the rostral brain. Rarefaction was accompanied by basement membrane thickening and perivascular collagen accumulation in type-1 DM; more severe blood-brain barrier leakage, and disruption of perivascular ECM organization, mainly of elastin and collagen fibers' structural integrity in the HFHS model. Our results point out that the downstream mechanisms of the long-term vascular complications of hyperglycemia models are structurally distinctive and may have implications for appropriate treatment options.Publication Open Access Is persistent post-COVID headache associated with protein-protein interactions between antibodies against viral spike protein and CGRP receptor?: a case report(Frontiers, 2022) Department of Chemical and Biological Engineering; N/A; Keskin, Özlem; Gürsoy, Attila; Özkan, Esra; Çelebi, Özlem; Özdemir, Yasemin Gürsoy; Faculty Member; Researcher; Doctor; Department of Chemical and Biological Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; College of Engineering; Koç University Hospital; 26605; 8745; N/A; N/A; 170592Background: after the acute pandemic of coronavirus disease 2019 (COVID-19), a wide variety of symptoms are identified under the term post-COVID syndrome, such as persistent headache. Post-COVID headache can be presented in a broad spectrum like headache attributed to systemic infection, chronification of already existing primary headache, or long-lasting, and also late-onset new daily persistent headache. Still, little is known about the pathophysiology of post-COVID headache, but activation of the trigeminovascular system may be one of the players. Case report: here, we present a case with a severe, long-lasting post-COVID headache and its sudden cessation with calcitonin gene-related peptide (CGRP) monoclonal antibody treatment. Conclusion: in our previous protein mimicry study, we have pointed at mimicry of virus spike protein and CGRP receptors. This mechanism may enlighten the current, common, and yet unsolved post-COVID headache cases.