Researcher: Özdemir, Yasemin Gürsoy
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Özdemir, Yasemin Gürsoy
Gürsoy-Özdemir, Yasemin
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Publication Metadata only The effect of P2X7 antagonism on subcortical spread of optogenetically-triggered cortical spreading depression and neuroinflammation(BMC, 2024) Uzay, Burak; Donmez-Demir, Buket; Ozcan, Sinem Yilmaz; Kocak, Emine Eren; Yemisci, Muge; Dalkara, Turgay; Karatas, Hulya; Özdemir, Yasemin Gürsoy; School of MedicineMigraine is a neurological disorder characterized by episodes of severe headache. Cortical spreading depression (CSD), the electrophysiological equivalent of migraine aura, results in opening of pannexin 1 megachannels that release ATP and triggers parenchymal neuroinflammatory signaling cascade in the cortex. Migraine symptoms suggesting subcortical dysfunction bring subcortical spread of CSD under the light. Here, we investigated the role of purinergic P2X7 receptors on the subcortical spread of CSD and its consequent neuroinflammation using a potent and selective P2X7R antagonist, JNJ-47965567. P2X7R antagonism had no effect on the CSD threshold and characteristics but increased the latency to hypothalamic voltage deflection following CSD suggesting that ATP acts as a mediator in the subcortical spread. P2X7R antagonism also prevented cortical and subcortical neuronal activation following CSD, revealed by bilateral decrease in c-fos positive neuron count, and halted CSD-induced neuroinflammation revealed by decreased neuronal HMGB1 release and decreased nuclear translocation of NF-kappa B-p65 in astrocytes. In conclusion, our data suggest that P2X7R plays a role in CSD-induced neuroinflammation, subcortical spread of CSD and CSD-induced neuronal activation hence can be a potential target.Publication Metadata only Experimental models to study immune dysfunction in the pathogenesis of Parkinson’s disease(Multidisciplinary Digital Publishing Institute (MDPI), 2024) Saponjic, Jasna; Mejías, Rebeca; Mikolovski, Neda; Dragic, Milorad; Canak, Asuman; Papoutsopoulou, Stamatia; Fladmark, Kari E.; Ntavaroukas, Panagiotis; Bayar Muluk, Nuray; Zeljkovic Jovanovic, Milica; Fontán-Lozano, Ángela; Comi, Cristoforo; Marino, Franca; Özdemir, Yasemin Gürsoy; School of MedicineParkinson’s disease (PD) is a chronic, age-related, progressive multisystem disease associated with neuroinflammation and immune dysfunction. This review discusses the methodological approaches used to study the changes in central and peripheral immunity in PD, the advantages and limitations of the techniques, and their applicability to humans. Although a single animal model cannot replicate all pathological features of the human disease, neuroinflammation is present in most animal models of PD and plays a critical role in understanding the involvement of the immune system (IS) in the pathogenesis of PD. The IS and its interactions with different cell types in the central nervous system (CNS) play an important role in the pathogenesis of PD. Even though culture models do not fully reflect the complexity of disease progression, they are limited in their ability to mimic long-term effects and need validation through in vivo studies. They are an indispensable tool for understanding the interplay between the IS and the pathogenesis of this disease. Understanding the immune-mediated mechanisms may lead to potential therapeutic targets for the treatment of PD. We believe that the development of methodological guidelines for experiments with animal models and PD patients is crucial to ensure the validity and consistency of the results.Publication Open Access Carbenoxolone mitigates extensive fibrosis formation in PLP-induced EAE model and multiple sclerosis serum-exposed pericyte culture(Frontiers Media Sa, 2024) Uçar, Ege Anıl; Özkan, Esra; Shomalizadeh, Narges; Şekerdağ, Emine; Akpunar, Fatmanur; Sapancı, Selin Selvi; Kesibi, Judy; Özler, Ceyda; Bilgez, Alara Su; Özdemir, Yasemin Gürsoy; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; Graduate School of Health SciencesIntroduction Multiple sclerosis (MS) is one of the most common causes of disability in young adults. Nearly, 85% of MS cases start with attacks and remissions, classified as relapsing-remitting multiple sclerosis (RRMS). With repeating attacks, MS causes brain-spinal cord atrophy and enhanced disability as disease progresses. PLP-induced EAE is one of the most established models for pathophysiology and treatment of RRMS. Recent studies demonstrated the possible role of pericytes in perivascular and intra-lesional fibrosis in PLP-induced EAE, whose importance remains elusive. Hence, we have investigated the possible role of pericytes in fibrosis formation and amelioration with a hemichannel blocker, Carbenoxolone (CBX).Methods PLP-induced experimental autoimmune encephalitis (EAE) model is used and the effect of CBX is investigated. Clinical scores were recorded and followed. Perivascular Collagen 1 and 3 accumulations were demonstrated as markers of fibrosis in the spinal cord. To delineate the role of pericytes, human brain vascular pericytes (HBVP) were incubated with the sera of MS patients to induce in-vitro MS model and the fibrosis formation was investigated.Results In the PLP induced in-vivo model, both intracerebroventricular and intraperitoneal CBX have significantly mitigated the disease progression followed by clinical scores, demyelination, and fibrosis. Moreover, CBX significantly mitigated MS-serum-induced fibrosis in the HBVP cell culture.Discussion The study demonstrated two important findings. First, CBX decreases fibrosis formation in both in-vivo and in-vitro MS models. Secondly, it improves neurological scores and decreases demyelination in the EAE model. Therefore, CBX can be potential novel therapeutic option in treating Multiple Sclerosis.Publication Metadata only Exosomes encapsulated in hydrogels for effective central nervous system drug delivery(Royal Soc Chemistry, 2024) Kocaarslan, Azra; Saghati, Sepideh; Yağcı, Yusuf; Rahbarghazi, Reza; Department of Mechanical Engineering; Department of Mechanical Engineering; Gargari, Ziba Zakeri; Metin, Ecem; Hosseinikarimi, Nasır Seyed; Vural, Atay; Akyoldaş, Göktuğ; Baysal, Kemal; Özdemir, Yasemin Gürsoy; Taşoğlu, Savaş; Sokullu, Emel; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; College of Sciences; School of Medicine; College of EngineeringThe targeted delivery of pharmacologically active molecules, metabolites, and growth factors to the brain parenchyma has become one of the major challenges following the onset of neurodegeneration and pathological conditions. The therapeutic effect of active biomolecules is significantly impaired after systemic administration in the central nervous system (CNS) because of the blood-brain barrier (BBB). Therefore, the development of novel therapeutic approaches capable of overcoming these limitations is under discussion. Exosomes (Exo) are nano-sized vesicles of endosomal origin that have a high distribution rate in biofluids. Recent advances have introduced Exo as naturally suitable bio-shuttles for the delivery of neurotrophic factors to the brain parenchyma. In recent years, many researchers have attempted to regulate the delivery of Exo to target sites while reducing their removal from circulation. The encapsulation of Exo in natural and synthetic hydrogels offers a valuable strategy to address the limitations of Exo, maintaining their integrity and controlling their release at a desired site. Herein, we highlight the current and novel approaches related to the application of hydrogels for the encapsulation of Exo in the field of CNS tissue engineering. The targeted delivery of pharmacologically active molecules, metabolites, and growth factors to the brain parenchyma has become one of the major challenges following the onset of neurodegeneration and pathological conditions.Publication Metadata only A multidisciplinary clinical approach to facioscapulohumeral muscular dystrophy orthopedic surgery in facioscapulohumeral dystrophy(Literatura Medica, 2018) N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; Çakmak, Özgür Öztop; Eren, İlker; Aslanger, Ayça Dilruba; Günerbüyük, Caner; Kayserili, Hülya; Oflazer, Piraye; Şar, Cüneyt; Demirhan, Mehmet; Özdemir, Yasemin Gürsoy; Faculty Member; Faculty Member; Doctor; Teaching Faculty; Faculty Member; Faculty Member; Doctor; Faculty Member; Faculty Member; School of Medicine; School of Medicine; N/A; School of Medicine; School of Medicine; School of Medicine; School of Medicine; School of Medicine; School of Medicine; Koc University Hospital; 107818; 168021; N/A; 380939; 7945; N/A; N/A; 9882; 170592Background - Impaired shoulder function is the most disabling problem for daily life of Fascioscapulohumeral muscular dystrophy (FSHD) patients. Scapulothoracic arthrodesis can give a high impact to the functionality of patients. Here we report our experience with scapulothoracic arthrodesis and spinal stenosis surgery in FSHD patients. Patients and methods - 32 FSHD patients were collected between 2015-2016. Demographical and clinical features were documented. All the patients were neurologically examined. The Medical Research Council (MRC) and the FSHD evaluation scale was used to assess muscle involvement(1). Scapulothoracic arthrodesis and spinal stenosis surgeries were performed in eligible patients. Results - There were 16 male and 16 female (mean age 34.4 years; range 12-73) patients. 6 shoulders of 4 patients aged between 2132 years underwent scapulothoracic arthrodesis (two bilateral, one left and one right sided). Only one 63 years old female patient with severe hyperlordosis had spinal fusion surgery. All of the patients undergoing these corrective surgeries have better functionality in daily life, as well as superior shoulder elevation. Conclusion - Until the emergence and clinical use of novel therapeutics, surgical interventions are indicated in carefully selected patients with FSHD to improve arm movements, the posture and the quality of life of patients in general. Scapulothorosic arthrodesis is a management with good clinical results and patient satisfaction. In selected cases other corrective orthopedic surgeries like spinal fusion may also be considered.Publication Metadata only Reversible transverse sinus collapse in a patient with idiopathic intracranial hypertension(BMJ Publishing Group, 2015) Önder, Halil; Göçmen, Rahşan; N/A; Özdemir, Yasemin Gürsoy; Faculty Member; School of Medicine; 170592The association of idiopathic intracranial hypertension (IIH) with stenosis or narrowing of the transverse sinuses (TSs) is well known. However, there is debate as to whether the stenosis is a cause or consequence. Here we describe a case of IIH and narrowing of the TSs, with four relapses and recoveries after repeated CSF diversions with lumbar puncture (LP) over 2 months. Subsequently, implantation of a lumboperitoneal shunt (LPrS) ensured recovery. MR venography 20 months after LPrS showed normally calibrated TSs. We show repeated MR venography findings before and after the LPs, and discuss the pathogenesis of IIH in terms of the cause and effect relationship between IIH and sinus collapse.Publication Metadata only Nose-to-brain delivery of farnesylthiosalicylic acid loaded hybrid nanoparticles in the treatment of glioblastoma(Elsevier Science Bv, 2017) Lüle, Sevda; Pehlivan, Sibel Bozdag; Kara, Aslı; Özturk, Naile; Kaffashi, Abbas; Vural, Imran; Yavuz, Burçin; Oğuz, Kader Karlı; Söylemezoğlu, Figen; Mut, Melike; Şekerdağ, Emine; Özdemir, Yasemin Gürsoy; PhD Student; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; School of Medicine; N/A; 170592Background: Effective treatments for gliomas are highly needed in research and clinical area in order to reach a high antineoplastic drug concentration at the target site without damaging healthy tissues. Intranasal (IN) administration, an alternative route for non-invasive drug delivery to the brain, bypasses the blood-brain-barrier (BBB) and eliminates systemic side effects. Objective: This study evaluated the antitumor efficacy of the RAS/MAPK inhibitor, farnesylthiosalicylic acid (FTA), loaded (lipid-cationic lipid-PEG-PLGA hybrid nanoparticles (HNPs) after IN versus IV application in tumor bearing rats. Patients and Methods / Material and Methods: FTA loaded HNPs were prepared, characterized and evaluated for their anticancer activity in vitro and in vivo and a biodistribution profile in rats was investigated. Results: Rat glioma bearing rats received either no treatment, a single dose or repeated treatments of 500 μM FTA loaded HNPs (~ 163.9 nm) via IN or IV application. After both single dose, and repeated treatments of IV and IN applied FTA loaded HNPs, significant tumor reduction was achieved. The biodistribution study of the same administration routes in healthy rats showed successful brain accumulation of FTA loaded HNPs with even higher presence in the olfactory bulb after nasal application. Furthermore, a lower accumulation was observed in the kidney and liver for nasal application compared to IV application. Conclusion: Herewith, we showed the potential and safer utility of IN application of FTA loaded HNPs as a non-invasive approach in glioblastoma treatment that bypasses both systemic toxicity and the BBB limitation by a direct transport route via the olfactory bulb to the brain.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 The role of pericytes in neurovascular unit: Emphasis on stroke(Bentham Science Publ Ltd, 2017) N/A; N/A; Çakmak, Özgür Öztop; Solaroğlu, İhsan; Özdemir, Yasemin Gürsoy; Faculty Member; Faculty Member; Faculty Member; School of Medicine; School of Medicine; School of Medicine; 299358; 102059; 170592Background: Among the central nervous system (CNS) disorders, diseases like ischemic and hemorrhagic stroke which are important health care problems as well as leading causes for emergency admissions, primarily affect neurovascular structure. Despite their high rate of mortality and morbidity, very few efficient treatment targets have been established until now. Objective: Blood-brain barrier (BBB) is the mostly effected structure in stroke as detected in both clinical studies and experimental settings. BBB is composed of endothelia, astrocyte end-foot, pericytes and basal lamina. Neurovascular unit, pericytes and BBB forming endothelia play significant pathophysiological roles in both ischemic and hemorrhagic stroke. Discussion: In this mini-review, the role of microcirculation and cells of blood-brain barrier in stroke pathophysiology will be discussed with a special emphasis based on pericytes. Pericytes are especially important for providing adequate microcirculatory supply according to needs of neuronal tissue and form one of the functionally important part of BBB and take role in neurovascular coupling. Understanding the role and disease producing mechanisms of neurovascular unit elements in different neurological conditions will provide novel targets for future treatments.Publication Metadata only Spreading depolarization waves in neurological diseases: a short review about its pathophysiology and clinical relevance(Bentham Science Publ Ltd, 2019) Taş, Yağmur Çetin; Solaroğlu, İhsan; Özdemir, Yasemin Gürsoy; Researcher; Faculty Member; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; School of Medicine; School of Medicine; N/A; 102059; 170592Lesion growth following acutely injured brain tissue after stroke, subarachnoid hemorrhage and traumatic brain injury is an important issue and a new target area for promising therapeutic interventions. Spreading depolarization or peri-lesion depolarization waves were demonstrated as one of the significant contributors of continued lesion growth. In this short review, we discuss the pathophysiology for SD forming events and try to list findings detected in neurological disorders like migraine, stroke, subarachnoid hemorrhage and traumatic brain injury in both human as well as experimental studies. Pharmacological and non-pharmacological treatment strategies are highlighted and future directions and research limitations are discussed.