Researcher:
Sarıkaya, Deniz

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Undergraduate Student

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Deniz

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Sarıkaya

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Sarıkaya, Deniz

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    PublicationOpen Access
    Effect of platelet-rich plasma injections versus placebo on pain and quality of life in patients with hip osteoarthritis: a double-blind, randomized clinical trial
    (Baycinar Medical Publ-Baycinar Tibbi Yayincilik, 2024) Sen, Ekin Ilke; Diracoglu, Demirhan; N/A; Topaloğlu, Mahir; Sarıkaya, Deniz; School of Medicine; Koç University Hospital
    Objectives: This study aims to compare the efficacy of intra-articular platelet -rich plasma (PRP) injections over a saline placebo in terms of reduction of pain and impact on quality of life among patients with hip osteoarthritis. Patients and methods: A total of 60 patients (29 males, 31 females, mean age: 57.9 +/- 7.3 years; range, 47 to 69 years) with known hip osteoarthritis of Kellgren-Lawrance (KL) Grades 2/3 were randomized into placebo (n=30) and PRP groups (n=30) between June 2014 and June 2015. Both groups received intra-articular injections into the hip joint under ultrasound guidance for three consecutive weeks. The patients were followed for six months, and pain reduction was assessed using the Visual Analog Scale (VAS), Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire, and Short Form Health Survey -36 (SF -36). Results: Intra-articular PRP treatment showed no advantage over a saline placebo in terms of VAS scores during activity. Both groups showed a significant improvement in VAS activity scores at one and six months. The placebo group showed improvements in VAS resting scores, whereas the PRP group did not. Both groups showed no improvement in WOMAC-total scores. Both groups showed no significant improvement across most SF -36 domains with the exception of improved physical role functioning at one month and general health at one and six months in the placebo group. Conclusion: Intra-articular injections of PRP show no significant difference compared to a saline placebo over a period of six months on pain, function, and quality of life scores in patients with hip osteoarthritis.
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    PublicationOpen Access
    Differentiation of post-polio syndrome from prior poliomyelitis sequela by assessing paraspinal muscle involvement in magnetic resonance imaging
    (MDPI, 2024) Terlemez, Rana; Cetin, Burak Ugur; Topaloğlu, Mahir; Sarıkaya, Deniz; Peker, Ahmet; Şentürk, Yunus Emre; Öğe, Ali Emre; Ketenci, Ayşegül; School of Medicine; Koç University Hospital
    Background/Objectives: Post-polio syndrome (PPS) affects former polio patients, manifesting decades after initial infection with progressive symptoms like pain, fatigue, and muscle weakness. Diagnosis relies on the clinical criteria and exclusion of other probable causes. The purpose of this study is to determine the scope and new diagnostic value of magnetic resonance imaging (MRI) in identifying muscle involvement in PPS and distinguishing it from prior poliomyelitis (PPM). Methods: This study was approved by the Koç University Ethics Committee with Approval No. 2023.409.IRB2.090. Electronic medical archives from two academic institutions were searched for records tagged with ICD code B-91 for poliomyelitis sequalae. The resulting search query of 291 records was manually sorted for PPS and PPM, medical history, clinical examination findings, and lumbar MR images down to 32 patients. Two independent radiologists evaluated the paraspinal musculature in the MRIs using the Mercuri scale. Inter-rater agreement, comparison of the paraspinal musculatures between groups, and their relationship to leg involvement were assessed with the resulting data. Results: Inter-rater agreement was found to be almost perfect across all muscles, except for the multifidus muscle. When clinical examination findings were included for these muscles, quadratus lumborum (QL) degradation was found in both right-side (p = 0.017) and left-side (p = 0.002) leg involvement. Conclusions: QL muscle deterioration may serve as a diagnostic marker for PPS, potentially guiding lumbar pain treatment through rehabilitation. © 2024 by the authors.
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    Extracellular vesicles derived from bone marrow mesenchymal stem cells enhance myelin maintenance after cortical injury in aged rhesus monkeys
    (Elsevier, 2021) Go, Veronica; Zhou, Yuxin; Bowley, Bethany G. E.; Pessina, Monica A.; Rosene, Douglas L.; Zhang, Zheng Gang; Chopp, Michael; Finklestein, Seth P.; Medalla, Maria; Buller, Benjamin; Moore, Tara L.; N/A; Sarıkaya, Deniz; Undergraduate Student; School of Medicine; N/A
    Cortical injury, such as stroke, causes neurotoxic cascades that lead to rapid death and/or damage to neurons and glia. Axonal and myelin damage in particular, are critical factors that lead to neuronal dysfunction and impair recovery of function after injury. These factors can be exacerbated in the aged brain where white matter damage is prevalent. Therapies that can ameliorate myelin damage and promote repair by targeting oligodendroglia, the cells that produce and maintain myelin, may facilitate recovery after injury, especially in the aged brain where these processes are already compromised. We previously reported that a novel therapeutic, Mesenchymal Stem Cell derived extracellular vesicles (MSC-EVs), administered intravenously at both 24 h and 14 days after cortical injury, reduced microgliosis (Go et at, 2019), reduced neuronal pathology (Medalla et al. 2020), and improved motor recovery (Moore et al. 2019) in aged female rhesus monkeys. Here, we evaluated the effect of MSC-EV treatment on changes in oligodendrocyte maturation and associated myelin markers in the sublesional white matter using immunohistochemistry, confocal microscopy, stereology, qRT-PCR, and ELISA. Compared to vehicle control monkeys, EV-treated monkeys showed a reduction in the density of damaged oligodendrocytes. Further, EV-treatment was associated with enhanced myelin maintenance, evidenced by upregulation of myelin-related genes and increases in actively myelinating oligodendrocytes in sublesional white matter. These changes in myelination correlate with the rate of motor recovery, suggesting that improved myelin maintenance facilitates this recovery. Overall, our results suggest that EVs act on oligodendrocytes to support myelination and improves functional recovery after injury in the aged brain. Significance: We previously reported that EVs facilitate recovery of function after cortical injury in the aged monkey brain, while also reducing neuronal pathology (Medalla et al. 2020) and microgliosis (Go et al. 2019). However, the effect of injury and EVs on oligodendrocytes and myelination has not been characterized in the primate brain (Doewar et al. 1999; Sozem et al. 2013). In the present study, we assessed changes in myelination after cortical injury in aged monkeys. Our results show, for the first time, that MSC-EVs support recovery of function after cortical injury by enhancing myelin maintenance in the aged primate brain.
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    Targeting the blood–brain barrier disruption in hypertension by ALK5/TGF-В type I receptor inhibitor SB-431542 and dynamin inhibitor dynasore
    (Elsevier, 2022) Ayvaz, Ecem; Yılmaz, Canan Uğur; Girouard, Helene; Atış, Müge; Akcan, Uğur; Altunsu, Deniz; Sarıkaya, Deniz; Temizyürek, Arzu; Ahıshalı, Bülent; Kaya, Mehmet; PHD Student; PHD Student; PHD Student; Undergraduate Student; Other; Faculty Member; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; Graduate School of Health Sciences; Graduate School of Health Sciences; School of Medicine; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; 9509; 10486
    Introduction: In this study, we aimed to target two molecules, transforming growth factor-beta (TGF-beta) and dynamin to explore their roles in blood-brain barrier (BBB) disruption in hypertension. Methods: For this purpose, angiotensin (ANG) II-induced hypertensive mice were treated with SB-431542, an inhibitor of the ALK5/TGF-beta type I receptor, and dynasore, an inhibitor of dynamin. Albumin-Alexa fluor 594 was used to assess BBB permeability. The alterations in the expression of claudin-5, caveolin (Cav)-1, glucose transporter (Glut)-1, and SMAD4 in the cerebral cortex and the hippocampus were evaluated by quantification of immunofluorescence staining intensity.Results: ANG II infusion increased BBB permeability to albumin-Alexa fluor 594 which was reduced by SB431542 (P < 0.01), but not by dynasore. In hypertensive animals treated with dynasore, claudin-5 immunofluorescence intensity increased in the cerebral cortex and hippocampus while it decreased in the cerebral cortex of SB-431542 treated hypertensive mice (P < 0.01). Both dynasore and SB-431542 prevented the increased Cav-1 immunofluorescence intensity in the cerebral cortex and hippocampus of hypertensive animals (P < 0.01). SB431542 and dynasore decreased Glut-1 immunofluorescence intensity in the cerebral cortex and hippocampus of mice receiving ANG II (P < 0.01). SB-431542 increased SMAD4 immunofluorescence intensity in the cerebral cortex of hypertensive animals, while in the hippocampus a significant decrease was noted by both SB-431542 and dynasore (P < 0.01).Conclusion: Our data suggest that inhibition of the TGF beta type I receptor prevents BBB disruption under hypertensive conditions. These results emphasize the therapeutic potential of targeting TGF beta signaling as a novel treatment modality to protect the brain of hypertensive patients.
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    The effects of the methyl-beta-cyclodextrin and myriocin on blood-brain barrier integrity in septic rats
    (Wiley, 2019) Yılmaz, Canan Uğur; Orhan, Nurcan; Kotil, Tuğba; Arıcan, Nadir; N/A; Akcan, Uğur; Atış, Müge; Sarıkaya, Deniz; Ahıshalı, Bülent; Kaya, Mehmet; PhD Student; PhD Student; Undergraduate Student; Faculty Member; Faculty Member; Graduate School of Health Sciences; Graduate School of Health Sciences; School of Medicine; School of Medicine; School of Medicine; N/A; 346431; N/A; 9509; 10486
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    Mesenchymal stem cell derived extracellular vesicles enhance myelin plasticity in rhesus monkeys
    (2020) Go, Veronica; Zhao, Yuxin; Bowley, Bethany; Medalla, Maria; Rosene, Douglas; Buller, Benjamin; Moore, Tara; N/A; Sarıkaya, Deniz; Undergraduate Student; School of Medicine; N/A
    Cortical injury, such as injury from stroke, results in a cascade of events that includes cell death, inflammation and disruption of myelin. To date, there are no highly effective treatments for reducing the deficits that occur after injury. Recently, we have demonstrated that extracellular vesicles (EVs) harvested from rhesus monkey bone marrow derived cells when given 1 day and 14 days following injury facilitate recovery of function in aged rhesus monkeys within the first 3–5 weeks after cortical injury. Based on these findings and current proteomic literature of MSC-EVs, we hypothesized that MSC-EVs enhance myelin plasticity by limiting damage to oligodendrocytes and stimulating remyelination. To assess general myelin integrity after injury, we used Spectral Confocal Reflectance Microscopy (SCoRe) to image myelinated axons and found an increase in the density of myelinated axons in the EV group (p < 0.05). To assess whether the difference was due to reduced damage or remyelination, in sublesional white matter we assessed immunohistochemical labeling of Olig2, a general oligodendrocyte marker, and 8OHdG, a marker for DNA damage. We found reduced densities of Olig2 colocalized with 8OHdG in the EV group (p<0.05). As a marker of active demyelination and myelin debris clearance, we measured Myelin Basic Protein (MBP) concentrations in CSF and found a longitudinal reduction in the EV animals. To assess remyelination, we measured expression of MBP, a gene for myelination in mature oligodendrocytes, Myelin Regulatory Factor (MyRF), a gene for oligodendrocyte differentiation and maintenance, and Breast Carcinoma Amplified Sequence 1 (BCAS1), a gene for newly myelinating oligodendrocytes. Interestingly, we found a 4 fold increase in MyRF expression, and a 1.5 fold increase in MBP and BCAS1 in the EV animals relative to the vehicle control animals in perilesional brain tissue. Consistent with these gene expression differences associated with re-myelination, we found that the densities of newly-myelinating oligodendrocytes immune-labeled with BCAS1, as well as mature oligodendrocytes expressing CC1, exhibited a trend towards an increase in the EV group (p = 0.09). These results suggest that EV treatment reduces myelin damage, while also stimulating myelin repair. Finally, these results correlated with enhanced motor recovery, suggesting that EV-mediated white matter plasticity is a critical component for recovery after cortical injury.