Research Outputs
Permanent URI for this communityhttps://hdl.handle.net/20.500.14288/2
Browse
28 results
Search Results
Publication Open Access Anti-inflammatory modulation of microglia via CD163-targeted glucocorticoids protects dopaminergic neurons in the 6-OHDA Parkinson's disease model(Society for Neuroscience, 2016) Tentillier, Noemie; Etzerodt, Anders; Olesen, Mads N.; Jacobsen, Jan; Bender, Dirk; Moestrup, Soren K.; Romero-Ramos, Marina; Department of Molecular Biology and Genetics; Rızalar, F. Sıla; Department of Molecular Biology and Genetics; Graduate School of Sciences and EngineeringIncreasing evidence supports a decisive role for inflammation in the neurodegenerative process of Parkinson's disease (PD). The immune response in PD seems to involve, not only microglia, but also other immune cells infiltrated into the brain. Indeed, we observed here the infiltration of macrophages, specifically CD163+ macrophages, into the area of neurodegeneration in the 6-hydroxydopamine (6-OHDA) PD model. Therefore, we investigated the therapeutic potential of the infiltrated CD163+ macrophages to modulate local microglia in the brain to achieve neuroprotection. To do so, we designed liposomes targeted for the CD163 receptor to deliver dexamethasone (Dexa) into the CD163+ macrophages in the 6-OHDA PD model. Our data show that a fraction of the CD163-targeted liposomes were carried into the brain after peripheral intravenous injection. The 6-OHDA-lesioned rats that received repeated intravenous CD163-targeted liposomes with Dexa for 3 weeks exhibited better motor performance than the control groups and had minimal glucocorticoid-driven side effects. Furthermore, these animals showed better survival of dopaminergic neurons in substantia nigra and an increased number of microglia expressing major histocompatibility complex II. Therefore, rats receiving CD163-targeted liposomes with Dexa were partially protected against 6-OHDA-induced dopaminergic neurodegeneration, which correlated with a distinctive microglia response. Altogether, our data support the use of macrophages for the modulation of brain neurodegeneration and specifically highlight the potential of CD163-targeted liposomes as a therapeutic tool in PD.Publication Open Access Anti-pan-neurofascin IgG3 as a marker of fulminant autoimmune neuropathy(Lippincott Williams and Wilkins (LWW), 2019) Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM)Objective: to identify and characterize patients with autoantibodies against different neurofascin (NF) isoforms. Methods: screening of a large cohort of patient sera for anti-NF autoantibodies by ELISA and further characterization by cell-based assays, epitope mapping, and complement binding assays. Results: two different clinical phenotypes became apparent in this study: The well-known clinical picture of subacute-onset severe sensorimotor neuropathy with tremor that is known to be associated with IgG4 autoantibodies against the paranodal isoform NF-155 was found in 2 patients. The second phenotype with a dramatic course of disease with tetraplegia and almost locked-in syndrome was associated with IgG3 autoantibodies against nodal and paranodal isoforms of NF in 3 patients. The epitope against which these autoantibodies were directed in this second phenotype was the common Ig domain found in all 3 NF isoforms. In contrast, anti-NF-155 IgG4 were directed against the NF-155-specific Fn3Fn4 domain. The description of a second phenotype of anti-NF-associated neuropathy is in line with some case reports of similar patients that were published in the last year. Conclusions: our results indicate that anti-pan-NF-associated neuropathy differs from anti-NF-155-associated neuropathy, and epitope and subclass play a major role in the pathogenesis and severity of anti-NF-associated neuropathy and should be determined to correctly classify patients, also in respect to possible differences in therapeutic response.Publication Open Access Antimuscarinic-induced convulsions in fasted rats after food intake: EEG patterns of fasting, scopolamine treatment, and convulsions(Galenos Yayınevi, 2022) Türkmen, Aslı Zengin; Nurten, Asiye; Edis, Bilge Özerman; Özen, İlknur; Kara, İhsan; Karamürsel, Sacit; Faculty Member; School of Medicine; 19597Objective: antimuscarinic treatment in fasted mice and rats causes clonic convulsion soon after food intake. This study was designed to evaluate the electrophysiological markers of these convulsions and fasting in electrocorticograms in rats. Methods: Male Wistar albino rats were stereotaxically implanted with 10 cortical electrodes, and baseline electroencephalogram recordings were taken for 10 minutes. After weighing, rats were deprived of food for 52 hours. At the 24th and 52nd hours of deprivation, continuous electroencephalogram recordings were repeated. After the deprivation period, animals were treated with saline or scopolamine (3 mg/kg). Twenty minutes after injections, animals were given food pellets. After eating food, electroencephalogram recordings were taken for 60 minutes and all animals were observed simultaneously to determine the incidence and onset of convulsions. Results: these results show that food deprivation for 52 hours decreased the amplitude of the gamma band when compared to basal (P <.05) and 24 hours (P <.008) food deprivation. And the amplitude of the beta band in the 52nd hour decreased when compared to the 24th hour of food deprivation (P <.05). The treatment with scopolamine changes the effects of food deprivation on the electroencephalogram. As a typical epileptiform manifestation, refeeding after scopolamine treatment caused a series of high-voltage polyspikes and synchronized spikes with a predominant frequency in the 1-3 Hz range. Conclusions: it was revealed that the behavioral patterns of rats and the electroencephalogram properties in these convulsions are in accordance with each other.Publication Open Access Brain atrophy and lesion burden are associated with disability progression in a multiple sclerosis real-world dataset using only T2-FLAIR: the NeuroSTREAM MSBase study(Elsevier, 2021) Barnett, M.; Bergsland, N.; Weinstock Guttman, B.; Butzkueven, H.; Kalıncık, T.; Desmond, P.; Gaillard, F.; van Pesch, V.; Özakbaş, S.; Rojas, JI.; Boz, C.; Wang, C.; Dwyer, MG.; Yang, S.; Jakimovski, D.; Kyle, K.; Ramasamy, DP.; Zivadinov, R.; Altıntaş, Ayşe; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; 11611Background: methodological challenges limit the use of brain atrophy and lesion burden measures in the followup of multiple sclerosis (MS) patients on clinical routine datasets. Objective: to determine the feasibility of T2-FLAIR-only measures of lateral ventricular volume (LVV) and salient central lesion volume (SCLV), as markers of disability progression (DP) in MS. Methods: a total of 3,228 MS patients from 9 MSBase centers in 5 countries were enrolled. Of those, 2,875 (218 with clinically isolated syndrome, 2,231 with relapsing-remitting and 426 with progressive disease subtype) fulfilled inclusion and exclusion criteria. Patients were scanned on either 1.5 T or 3 T MRI scanners, and 5,750 brain scans were collected at index and on average after 42.3 months at post-index. Demographic and clinical data were collected from the MSBase registry. LVV and SCLV were measured on clinical routine T2-FLAIR images. Results: longitudinal LVV and SCLV analyses were successful in 96% of the scans. 57% of patients had scanner related changes over the follow-up. After correcting for age, sex, disease duration, disability, disease-modifying therapy and LVV at index, and follow-up time, MS patients with DP (n = 671) had significantly greater absolute LVV change compared to stable (n = 1,501) or disability improved (DI, n = 248) MS patients (2.0 mL vs. 1.4 mL vs. 1.1 mL, respectively, ANCOVA p < 0.001, post-hoc pair-wise DP vs. Stable p = 0.003; and DP vs. DI, p = 0.002). Similar ANCOVA model was also significant for SCLV (p = 0.03). Conclusions: LVV-based atrophy and SCLV-based lesion outcomes are feasible on clinically acquired T2-FLAIR scans in a multicenter fashion and are associated with DP over mid-term.
Publication Metadata only Challenges of the nose-to-brain route(Academic Press Ltd-Elsevier Science Ltd, 2017) Şekerdağ, Emine; PhD Student; Graduate School of Health Sciences; N/AThe main goal for investigating new techniques for brain drug delivery is to improve and/or elevate treatment outcomes. Targeted nose-to-brain delivery is a potential noninvasive drug delivery technique with many benefits, such as optimized drug distribution, reduced side effects, and improved patient compliance. Despite the fact that transport mechanism of drugs administered nasally are not fully understood, this pathway is still under investigation by many research groups to optimize the search for evidence and/or improve the direct nose-to-brain route. The most important challenges are translating study designs and obtaining data. Furthermore, the low drug uptake by the brain and environmental tissues in the nasal cavity is an issue that needs to be overcome by the utilization of nanotechnology-based techniques, which incorporate drugs in nanoparticles and or other drug delivery systems.Publication Open Access Changes in the expression of c-fos and AQP4 in the hippocampus and amygdala regions of rats with kainic acid-induced temporal lobe epilepsy and their role in the pathogenesis of disease(Galenos Yayınevi, 2022) Taşkıran, Emine; Yılmaz, Canan Uğur; Orhan, Nurcan; Kaya, Mehmet; Arıcan, Nadir; Bahçeci, Metin Berkant; Kaya, Mehmet; Gürses, Rabia Candan; Ahıshalı, Bülent; Faculty Member; Faculty Member; Faculty Member; School of Medicine; 10486; 110149; N/AObjective: aquaporin4 is the main water channel in the brain that is associated with neurological disorders. The role and the expressive changes of aquaporin4 in epilepsy are still limited and controversial. The study aims to evaluate the expression of c-fos and aquaporin4 during epileptogenesis after systemic kainic acid-induced status epilepticus in the temporal lobe epilepsy animal model and to investigate their alterations in both hippocampus and amygdala. Methods: intraperitoneal injections of kainic acid (5-15 mg/kg) by repeated low kainic acid protocol were given to young adult 32 Wistar albino rats for status epilepticus. Aquaporin4 and c-fos were investigated in the hippocampus and amygdala on days 1 and 60 after status epilepticus by immunostaining methods in brain slices. Results: the intensity of c-fos immunostaining rose considerably in the hippocampus CA1 area of rats during the acute period (P < 0.05) and in the amygdala during the chronic period. The immunostaining intensity of aquaporin4in the hippocampus of rats with acute kainic acid increased significantly (P <.05). It was also raised in the hippocampal region of the rats in the acute sham and chronic kainic acid groups. Discussion: the results of this study support a link between aquaporin4 and epilepsy. It can be speculated that aquaporin4 change is primarily a defense mechanism immediately after status epilepticus, and then, it can evolve into a causal factor with exhaustion as a result of overuse.Publication Open Access Collaborative international research in clinical and longitudinal experience study in NMOSD(Lippincott Williams and Wilkins (LWW), 2019) Cook, Lawrence J.; Rose, John W.; Alvey, Jessica S.; Jolley, Anna Marie; Kuhn, Renee; Marron, Brie; Pederson, Melissa; Enriquez, Rene; Yearley, Jeff; McKechnie, Stephen; Han, May H.; Tomczak, Anna J.; Levy, Michael; Mealy, Maureen A.; Coleman, Jessica; Bennett, Jeffrey L.; Johnson, Ruth; Barnes-Garcia, Myka; Traboulsee, Anthony L.; Carruthers, Robert L.; Lee, Lisa Eunyoung; Schubert, Julia J.; McMullen, Katrina; Kister, Ilya; Rimler, Zoe; Reid, Allyson; Sicotte, Nancy L.; Planchon, Sarah M.; Cohen, Jeffrey A.; Ivancic, Diane; Sedlak, Jennifer L.; Sand, Ilana Katz; Repovic, Pavle; Amezcua, Lilyana; Pruitt, Ana; Amundson, Erika; Chitnis, Tanuja; Mullin, Devin S.; Klawiter, Eric C.; Russo, Andrew W.; Riley, Claire S.; Onomichi, Kaho B.; Levine, Libby; Nelson, Katherine E.; Nealon, Nancy M.; Engel, Casey; Kruse-Hoyer, Mason; Marcille, Melanie; Tornes, Leticia; Rumpf, Anne; Greer, Angela; Behne, Megan Kenneally; Rodriguez, Renee R.; Behne, Daniel W.; Blackway, Derek W.; Coords, Brian; Blaschke, Terrence F.; Sheard, Judy; Smith, Terry J.; Behne, Jacinta M.; Yeaman, Michael R.; Abboud, Hesham; Aktas, Orhan; Altintas, Ayse; Apiwattanakul, Metha; Asgari, Nasrin; Banwell, Brenda; Bichuetti, Denis; Bowen, James; Broadley, Simon; Bruck, Wolfgang; Cabre, Philippe; Cohen, Jeffrey; De Seze, Jerome; Delgado-Garcia, Guillermo; Basuroski, Irena Dujmovic; Fujihara, Kazuo; Goodman, Andrew; Havla, Joachim; Hellwig, Kerstin; Hintzen, Rogier; Hooper, D. Craig; Iorio, Raffaele; Jacob, Anu; Jarius, Sven; Jimenez Arango, Jorge Andres; John, Gareth; Kim, Ho Jin; Kim, Sung Min; Kimbrough, Dorian J.; Kissani, Najib; Kleiter, Ingo; Lana-Peixoto, Marco; Leite, M. Isabel; Liu, Yaou; Lublin, Fred; Maiga, Youssoufa; Mao-Draayer, Yang; Marignier, Romain; Matiello, Marcelo; Momtazee, Callene; Morrow, Mark; Nakashima, Ichiro; O'Connor, Kevin; Oreja-Guevara, Celia; Palace, Jacqueline; Pandit, Lekha; Paul, Friedemann; Prayoonwiwat, Naraporn; Probstel, Anne-Katrin; Qian, Peiqing; Quan, Chao; Ringelstein, Marius; Rivera, Victor; Rotstein, Dalia L.; Ruprecht, Klemens; Sa, Maria Jose; Saiz, Albert; Serguera, Che; Shosha, Eslam; Siritho, Sasitorn; Siva, Aksel; Soto de Castillo, Ibis; Stuve, Olaf; Tenembaum, Silvia; Villoslada, Pablo; Wingerchuk, Dean; Wuerfel, Jens; Yeh, E. Ann; Zamvil, Scott S.; Langer-Gould, Annette; N/A; Altıntaş, Ayşe; Faculty Member; School of Medicine; 11611Objective to develop a resource of systematically collected, longitudinal clinical data and biospecimens for assisting in the investigation into neuromyelitis optica spectrum disorder (NMOSD) epidemiology, pathogenesis, and treatment. Methods to illustrate its research-enabling purpose, epidemiologic patterns and disease phenotypes were assessed among enrolled subjects, including age at disease onset, annualized relapse rate (ARR), and time between the first and second attacks. Results as of December 2017, the Collaborative International Research in Clinical and Longitudinal Experience Study (CIRCLES) had enrolled more than 1,000 participants, of whom 77.5% of the NMOSD cases and 71.7% of the controls continue in active follow-up. Consanguineous relatives of patients with NMOSD represented 43.6% of the control cohort. Of the 599 active cases with complete data, 84% were female, and 76% were anti-AQP4 seropositive. The majority were white/Caucasian (52.6%), whereas blacks/African Americans accounted for 23.5%, Hispanics/Latinos 12.4%, and Asians accounted for 9.0%. The median age at disease onset was 38.4 years, with a median ARR of 0.5. Seropositive cases were older at disease onset, more likely to be black/African American or Hispanic/Latino, and more likely to be female. Conclusions collectively, the CIRCLES experience to date demonstrates this study to be a useful and readily accessible resource to facilitate accelerating solutions for patients with NMOSD.Publication Open Access Cortical spreading depression can be triggered by sensory stimulation in primed wild type mouse brain: a mechanistic insight to migraine aura generation(BioMed Central, 2022) Hanalioğlu, Şahin; Sağ, Aslıhan Taşkıran; Karataş, Hülya; Demir, Buket Dönmez; Özcan, Sinem Yılmaz; Koçak, Emine Eren; Dalkara, Turgay; Özdemir, Yasemin Gürsoy; Faculty Member; Researcher; Faculty Member; School of Medicine; 170592Background: unlike the spontaneously appearing aura in migraineurs, experimentally, cortical spreading depression (CSD), the neurophysiological correlate of aura is induced by non-physiological stimuli. Consequently, neural mechanisms involved in spontaneous CSD generation, which may provide insight into how migraine starts in an otherwise healthy brain, remain largely unclear. We hypothesized that CSD can be physiologically induced by sensory stimulation in primed mouse brain. Methods: cortex was made susceptible to CSD with partial inhibition of Na+/K+-ATPase by epidural application of a low concentration of Na+/K+-ATPase blocker ouabain, allowing longer than 30-min intervals between CSDs or by knocking-down ?2 subunit of Na+/K+-ATPase, which is crucial for K+ and glutamate re-uptake, with shRNA. Stimulation-triggered CSDs and extracellular K+ changes were monitored in vivo electrophysiologically and a K+-sensitive fluoroprobe (IPG-4), respectively. Results: after priming with ouabain, photic stimulation significantly increased the CSD incidence compared with non-stimulated animals (44.0 vs. 4.9%, p < 0.001). Whisker stimulation also significantly increased the CSD incidence, albeit less effectively (14.9 vs. 2.4%, p = 0.02). Knocking-down Na+/K+-ATPase (50% decrease in mRNA) lowered the CSD threshold in all mice tested with KCl but triggered CSDs in 14.3% and 16.7% of mice with photic and whisker stimulation, respectively. Confirming Na+/K+-ATPase hypofunction, extracellular K+ significantly rose during sensory stimulation after ouabain or shRNA treatment unlike controls. In line with the higher CSD susceptibility observed, K+ rise was more prominent after ouabain. To gain insight to preventive mechanisms reducing the probability of stimulus-evoked CSDs, we applied an A1-receptor antagonist (DPCPX) to the occipital cortex, because adenosine formed during stimulation from ATP can reduce CSD susceptibility. DPCPX induced spontaneous CSDs but only small-DC shifts along with suppression of EEG spikes during photic stimulation, suggesting that the inhibition co-activated with sensory stimulation could limit CSD ignition when K+ uptake was not sufficiently suppressed as with ouabain. Conclusions: normal brain is well protected against CSD generation. For CSD to be ignited under physiological conditions, priming and predisposing factors are required as seen in migraine patients. Intense sensory stimulation has potential to trigger CSD when co-existing conditions bring extracellular K+ and glutamate concentrations over CSD-ignition threshold and stimulation-evoked inhibitory mechanisms are overcome.Publication Metadata only Difficulties faced in standardized receptor stimulation and in standardized analysis of muscle responses to a stimulus(Springer international Publishing ag, 2017) Türker, Kemal Sıtkı; Faculty Member; School of Medicine; 6741This presentation will cover the methods used to investigate neuronal circuitries between peripheral receptors and skeletal muscles in human subjects. there are a number of problems regarding reflex studies using experimental animals. there are also problems in the recording and analysis aspects of these experiments. To overcome these problems we have utilized precisely-controlled mechanical or electrical stimuli to activate receptors and single motor units from human muscles. We also used classical and novel methods to analyze the results to indicate neuronal networks.Publication Open Access Erratum: Age-dependent decline in learning and memory performances of WAG/Rij rat model of absence epilepsy [Behav Brain Funct. 8 (2012) 51](BioMed Central, 2015) Karson, Ayşe Balcı; Utkan, Tijen; Arıcıoğlu, Feyza; Ateş, Nurbay; Balcı, Fuat; Faculty Member; College of Social Sciences and Humanities; 51269
- «
- 1 (current)
- 2
- 3
- »