Researcher:
Ahıshalı, Bülent

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Bülent

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Ahıshalı

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Ahıshalı, Bülent

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2019 - 201932020 - 20229

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Now showing 1 - 10 of 12
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    The effects of histamine receptor antagonists and RhoA inhibitor on histamine-induced blood-brain barrier disruption
    (Wiley, 2022) Polat, Fidan Şeker; Yılmaz, Canan Uğur; N/A; N/A; N/A; N/A; N/A; N/A; N/A; Department of Chemistry; Akcan, Uğur; Temizyürek, Arzu; Özen, Deniz; Demirci, Gözde; Akbulak, İrem; Üzbe, Ayşe Selin; Üzbe, Pakize Pelin; Acar, Havva Funda Yağcı; Kaya, Mehmet; Ahıshalı, Bülent; PhD Student; Other; Other; Master Student; Master Student; Other; Other; Faculty Member; Faculty Member; Faculty Member; Department of Chemistry; Graduate School of Health Sciences; School of Medicine; N/A; Graduate School of Sciences and Engineering; N/A; N/A; N/A; College of Sciences; School of Medicine; School of Medicine; Koç University Hospital; N/A; 357912; N/A; N/A; N/A; N/A; N/A; 178902; 10486; 9509
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    Basic physiology of the blood-brain barrier in health and disease: a brief overview
    (Taylor and Francis inc, 2021) N/A; N/A; Kaya, Mehmet; Ahıshalı, Bülent; 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; 10486; 9509
    The blood-brain barrier (BBB), a dynamic interface between blood and brain constituted mainly by endothelial cells of brain microvessels, robustly restricts the entry of potentially harmful blood-sourced substances and cells into the brain, however, many therapeutically active agents concurrently cannot gain access into the brain at effective doses in the presence of an intact barrier. On the other hand, breakdown of BBB integrity may involve in the pathogenesis of various neurodegenerative diseases. Besides, certain diseases/disorders such as Alzheimer's disease, hypertension, and epilepsy are associated with varying degrees of BBB disruption. In this review, we aim to highlight the current knowledge on the cellular and molecular composition of the BBB with special emphasis on the major transport pathways across the barrier type endothelial cells. We further provide a discussion on the innovative brain drug delivery strategies in which the obstacle formed by BBB interferes with effective pharmacological treatment of neurodegenerative diseases/disorders.
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    The strategies of drug targeting into the brain through the blood-brain barrier in drug-resistant epilepsy
    (Wiley, 2019) Yılmaz, Canan Uğur; Emik, Serkan; Orhan, Nurcan; Arican, Nadir; Temizyürek, Arzu; Ahıshalı, Bülent; Akcan, Uğur; Atış, Müge; Gürses, Rabia Candan; Kaya, Mehmet; Other; Faculty Member; PhD Student; PhD Student; Faculty Member; Faculty Member; School of Medicine; School of Medicine; Graduate School of Health Sciences; Graduate School of Health Sciences; School of Medicine; School of Medicine; 357912; 9509; N/A; 346431; 110149; 10486
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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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    The effects of magnesium sulfate on cyclophosphamide-induced ovarian damage: Folliculogenesis
    (Elsevier, 2020) Yılmaz, Tuğba Ekiz; Taşdemir, Müge; Arıcan, Nadir; N/A; Kaya, Mehmet; Ahıshalı, Bülent; Faculty Member; Faculty Member; School of Medicine; School of Medicine; 10486; 9509
    Cyclophosphamide (CYP) is one of the alkylating chemotherapeutic agents and its adverse effects on folliculogenesis in the ovary are well-known due to the previous scientific research on this topic. Magnesium has various effects in organisms, including catalytic functions on the activation and inhibition of many enzymes, and regulatory functions on cell proliferation, cell cycle, and differentiation. In this study, the effects of magnesium sulfate (MgSO4) on CYP induced ovarian damage were investigated. Immature Wistar-Albino female rats of 28-days were treated with pregnant mare serum gonadotrophin (PMSG) to develop the first generation of preovulatory follicles. Rats of the experimental groups were then treated with either CYP (100 mg/kg, i.p) and MgSO4 (270 mg/kg loading dose; 27 mg/kg maintenance doseX12, i.p) solely or in combination. Following in-vivo 5-bromo-2-deoxyuridine (BrdU) labeling, animals were sacrificed and ovaries were embedded in paraffin and Epon. In the ovaries, added to the evaluation of general morphology and follicle count; BrdU and TUNEL-labeling, cleaved caspase-3 and p27 (cyclin-dependent kinase inhibitor) staining was also performed immunohistochemically and an ultrastructural evaluation was performed by transmission electron microscopy (TEM). The number of primordial follicles were decreased and multilaminar primary and atretic follicles were increased in CYP group. After MgSO4 treatment, while primordial follicle pool were elevated, the number of atretic follicles were decreased. Additionally, decreased BrdU-labeling, increased cleaved caspase 3 immunoreactivity and increased TUNEL labeling were observed in CYP group. In CYP treated animals, observations showed that while MgSO4 administration caused no alterations in BrdU proliferation index and caspase-3 immunoreactivity, it significantly reduced the TUNEL labeling. It was also observed that, while p27 immunoreactivity significantly increased in the nuclei of granulosa and theca cells in the CYP group; MgSO4 treatment significantly reduced these immunoreactivities. The ultrastructural observations showed frequent apoptotic profiles in granulosa and theca cells in both early and advanced stages of follicles in the CYP group and the MgSO4 treatment before the CYP application led to ultrastructural alleviation of the apoptotic process. In conclusion, our data suggest that MgSO4 may provide an option of pharmacologic treatment for fertility preservation owing to the beneficial effects of on chemotherapy-induced accelerated follicular apoptotic process, and the protection of the primordial follicle pool.
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    Blood brain barrier dynamics and antiepileptogenic effects of antiepileptic drug-bound nanoparticle in WAG/Rij rats as a genetic absence epilepsy model
    (Wiley, 2019) Yılmaz, Canan Uğur; Orhan, Nurcan; Arican, Nadir; Temizyürek, Arzu; Akcan, Uğur; Atış, Müge; Ahıshalı, Bülent; Kaya, Mehmet; Other; PhD Student; PhD Student; Faculty Member; Faculty Member; School of Medicine; Graduate School of Health Sciences; Graduate School of Health Sciences; School of Medicine; School of Medicine; 357912; N/A; 346431; 9509; 10486
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    The effects of CLP-induced sepsis on proliferation and apoptosis of granulosa and theca cells in rat ovary: a histochemical and ultrastructural study
    (Elsevier, 2020) Taşdemir, Müge; Ekiz-Yılmaz, Tuğba; Uğur-Yılmaz, Canan; Orhan, Nurcan; Doğan, Mehmet Ali; Arıcan, Nadir; N/A; Kaya, Mehmet; Ahıshalı, Bülent; Faculty Member; Faculty Member; School of Medicine; School of Medicine; 10486; 9509
    Sepsis is defined as a systemic inflammatory response to infection. This study is aimed to evaluate the effects of experimental sepsis on the proliferation and apoptosis of granulosa and theca cells in the rat ovary.
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    Targeted delivery of lacosamide-conjugated gold nanoparticles into the brain in temporal lobe epilepsy in rats
    (Elsevier, 2020) Yılmaz, Canan Uğur; Emik, Serkan; Orhan, Nurcan; Arican, Nadir; Küçük, Mutlu; N/A; N/A; N/A; Department of Chemistry; N/A; N/A; N/A; Temizyürek, Arzu; Atış, Müge; Akcan, Uğur; Khodadust, Rouhollah; Gürses, Rabia Candan; Ahıshalı, Bülent; Kaya, Mehmet; Other; PhD Student; PhD Student; Other; Faculty Member; Faculty Member; Faculty Member; Department of Chemistry;  Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; Graduate School of Health Sciences; Graduate School of Health Sciences; College of Sciences; School of Medicine; School of Medicine; School of Medicine; 357912; 346431; N/A; N/A; 110149; 9509; 10486
    Temporal lobe epilepsy (TLE) is the most common form of epilepsy with focal seizures, and currently available drugs may fail to provide a thorough treatment of the patients. The present study demonstrates the utility of glucose-coated gold nanoparticles (GNPs) as selective carriers of an antiepileptic drug, lacosamide (LCM), in developing a strategy to cross the blood-brain barrier to overcome drug resistance. Intravenous administration of LCM-loaded GNPs to epileptic animals yielded significantly higher nanoparticle levels in the hippocampus compared to the nanoparticle administration to intact animals. The amplitude and frequency of EEG-waves in both ictal and interictal stages decreased significantly after LCM-GNP administration to animals with TLE, while a decrease in the number of seizures was also observed though statistically insignificant. In these animals, malondialdehyde was unaffected, and glutathione levels were lower in the hippocampus compared to sham. Ultrastructurally, LCM-GNPs were observed in the brain parenchyma after intravenous injection to animals with TLE. We conclude that glucose-coated GNPs can be efficient in transferring effective doses of LCM into the brain enabling elimination of the need to administer high doses of the drug, and hence, may represent a new approach in the treatment of drug-resistant TLE.
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    Evaluation of blood-brain barrier integrity using vascular permeability markers: evans blue, sodium fluorescein, albumin-alexa fluor conjugates, and horseradish peroxidase
    (Humana Press Inc, 2021) N/A; N/A; Ahıshalı, Bülent; Kaya, Mehmet; Faculty Member; Faculty Member; School of Medicine; School of Medicine; 9509; 10486
    The blood-brain barrier (BBB) constituted by endothelial cells of brain microvessels is a dynamic interface, which controls and regulates the transport of various substances including peptides, proteins, ions, vitamins, hormones, and immune cells from the circulation into the brain parenchyma. Certain diseases/disorders such as Alzheimer's disease, sepsis, and hypertension can lead to varying degrees of BBB disruption. Moreover, impairment of BBB integrity has been implicated in the pathogenesis of various neurodegenerative diseases like epilepsy. In attempts to explore the wide spectrum of pathophysiologic mechanisms of these diseases/disorders, a variety of experimental insults targeted to the BBB integrity in vitro in cell culture models and in vivo in laboratory animals have been shown to alter BBB permeability causing enhanced transport of certain tracers such as sodium fluorescein, cadaverine-Alexa fluor, horseradish peroxidase, FITC-dextran, albumin-Alexa fluor conjugates, and Evans blue dye across the barrier. The permeability changes in barrier-type endothelial cells can be assessed by intravascular infusion of exogenous tracers and subsequent detection of the extravasated tracer in the brain tissue, which enable functional and structural analysis of BBB integrity. In this chapter, we aimed to highlight the current knowledge on the use of four most commonly performed tracers, namely, Evans blue, sodium fluorescein, albumin-Alexa fluor conjugates, and horseradish peroxidase. The experimental methodologies that we use in our laboratory for the detection of these tracers by macroscopy, spectrophotometry, spectrophotofluorometry, confocal laser scanning microscopy, and electron microscopy are also discussed. Tracing studies at the morphological level are mainly aimed at the identification of the tracers both in the barrier-related cells and brain parenchyma. In addition, BBB permeability to the tracers can be quantified using spectrophotometric and spectro-photofluorometric assays and image analysis by confocal laser scanning microscopy and electron microscopy. The results of our studies conducted under various experimental settings using the mentioned tracers indicate that barrier-type endothelial cells in brain microvessels orchestrate the paracellular and/or transcellular trafficking of substances across BBB. These efforts may not only contribute to designing approaches for the management of diseases/disorders associated with BBB breakdown but may also provide new insights for developing novel brain drug delivery strategies.