TY - JOUR AU - Törteli, Anna AU - Bálint, Armand Rafael AU - Tóth, Réka AU - Makra, Péter AU - Bari, Ferenc AU - Farkas, Eszter AU - Menyhárt, Ákos TI - REPERFUSION FAILURE AFTER SPREADING DEPOLARIZATION SHAPES HEMOGLOBIN CONTENT IN THE MOUSE CORTEX JF - IBRO NEUROSCIENCE REPORTS J2 - IBRO NEUROSCI REP VL - 15 PY - 2023 IS - Suppl. 1. SP - S653 EP - S653 SN - 2667-2421 DO - 10.1016/j.ibneur.2023.08.1306 UR - https://m2.mtmt.hu/api/publication/34437579 ID - 34437579 LA - English DB - MTMT ER - TY - JOUR AU - Frank, Rita AU - Pesti, István AU - Menyhárt, Ákos AU - Szarvas, Péter AU - Gulya, Károly AU - Bari, Ferenc AU - Farkas, Eszter TI - Nimodipine exerts a protective effect against spreading depolarization and neuroinflammation JF - PHYSIOLOGY J2 - PHYSIOLOGY VL - 38 PY - 2023 IS - S1 SP - 100 EP - 100 PG - 1 SN - 1548-9213 DO - 10.1152/physiol.2023.38.S1.5762940 UR - https://m2.mtmt.hu/api/publication/34213830 ID - 34213830 AB - Hypothesis, objective: Voltage gated Ca2+ channels (VGCCs) are widely expressed in the central nervous system and implicated in neuronal injury and microglial activation. Nimodipine, a potent cerebrovascular dilator and VGCC antagonist is found to be effective against the vasoconstriction caused by spreading depolarization (SD) in preclinical studies of ischemia. However, it is still unclear whether the beneficial effect of nimodipine is achieved by the improvement of perfusion or a direct action on neuronal or glial cells. Our aim was to explore the direct action of nimodipine on the nervous tissue and microglia. Methods: Brain slices prepared from C57BL/6 mice (n=16) were perfused with artificial cerebrospinal fluid (aCSF). After 30 min nimodipine (nimo; 10 μM) incubation, low glucose aCSF (5 mM) and transient anoxia (1 min) were applied to mimic ischemia and to elicit SD. Intrinsic optical signal imaging was used to analyze SD features, TTC staining was applied to assess tissue injury. Primary mixed and pure microglia cultures prepared from the cortex of neonatal SPRD rats were treated with lipopolysaccharide (LPS;20 ng/ml) and nimodipine (5,10,20 μM), alone or in combination for 24 h. Microglial activation was evaluated by Iba1 immunolabeling (degree of arborization expressed by a transformation index (TI)), Western blot analysis and the visualization of phagocytosis with fluorescent microbeads. Results: In brain slices, nimodipine reduced the focal area of SD (2.37±0.94 vs 3.38±0.88%, nimo vs control), the total cortical area affected by SD (17.12±8.63 vs 39.88±22.42%, nimo vs control) and the propagation velocity of SD (0.19±0.79 vs 1.59±2.29mm/min, nimo vs control). Nimodipine decreased tissue injury, viability expressed as the number of TTC-stained particles (4.48±1.45 vs 3.52±1.52 particle/1000 μm2, nimo vs control). Nimodipine reduced microglial activation in LPS-treated cultures reflected by more ramified cell morphology (3.1±0.91 vs 1.89±0.41 TI, LPS+nimo vs LPS), decreased Iba1 intensity in Western blot analysis (108.3±20.1 and 77.2±8.49 vs 213.4±29.7 integrated optical density, LPS+nimo 10 and 20 μM vs LPS) and attenuated phagocytic activity (6±10 vs 22±20 bead/cell LPS+nimo vs LPS). Conclusion: Nimodipine was protective against SD and successfully reduced neuroinflammation by decreasing microglial activation. Neuroprotection was achieved independent of nimodipine’s vascular action. Our data suggest that nimodipine may be applicable against neuroinflammation and ischemia, in which neurodegeneration is believed to be linked to neurotoxic microglial activation. LA - English DB - MTMT ER - TY - JOUR AU - Kecskés, Szilvia AU - Menyhárt, Ákos AU - Bari, Ferenc AU - Farkas, Eszter TI - Nimodipine augments cerebrovascular reactivity in aging but runs the risk of local perfusion reduction in acute cerebral ischemia JF - FRONTIERS IN AGING NEUROSCIENCE J2 - FRONT AGING NEUROSCI VL - 15 PY - 2023 PG - 14 SN - 1663-4365 DO - 10.3389/fnagi.2023.1175281 UR - https://m2.mtmt.hu/api/publication/33803477 ID - 33803477 N1 - Cerebral Blood Flow and Metabolism Research Group, Hungarian Centre of Excellence for Molecular Medicine – University of Szeged, Szeged, Hungary Department of Cell Biology and Molecular Medicine, Albert Szent-Györgyi Medical School and Faculty of Science and Informatics, University of Szeged, Szeged, Hungary Department of Medical Physics and Informatics, Albert Szent-Györgyi Medical School and Faculty of Science and Informatics, University of Szeged, Szeged, Hungary Export Date: 8 March 2024 Correspondence Address: Farkas, E.; Cerebral Blood Flow and Metabolism Research Group, Hungary; email: eszter.farkas@hcemm.eu Chemicals/CAS: carbon dioxide, 124-38-9, 58561-67-4; nimodipine, 66085-59-4 Funding details: Horizon 2020 Framework Programme, H2020, 739593 Funding details: Magyar Tudományos Akadémia, MTA Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH, FK142218, K134334, K134377 Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA, TKP2021-EGA-28 Funding details: Szent-Györgyi Albert Orvostudományi Kar, Szegedi Tudományegyetem Funding text 1: The EU’s Horizon 2020 research and innovation program no. 739593; grants from the National Research, Development and Innovation Office of Hungary (nos. K134377, K134334 and FK142218); the Ministry of Innovation and Technology of Hungary and the National Research, Development and Innovation Fund (no. TKP2021-EGA-28 financed under the TKP2021-EGA funding scheme); the National Brain Research Program 3.0 of the Hungarian Academy of Sciences; and the Research Fund of the Albert Szent-Györgyi Medical School, University of Szeged, Hungary. LA - English DB - MTMT ER - TY - JOUR AU - Menyhárt, Ákos AU - Bálint, Armand Rafael AU - Kozák, Péter AU - Bari, Ferenc AU - Farkas, Eszter TI - Nimodipine accelerates the restoration of functional hyperemia during spreading oligemia JF - JOURNAL OF NEUROCHEMISTRY J2 - J NEUROCHEM PY - 2023 PG - 11 SN - 0022-3042 DO - 10.1111/jnc.15792 UR - https://m2.mtmt.hu/api/publication/33691203 ID - 33691203 N1 - Hungarian Centre of Excellence for Molecular Medicine—University of Szeged, Cerebral Blood Flow and Metabolism Research Group, Szeged, Hungary Department of Cell Biology and Molecular Medicine, Albert Szent-Györgyi Medical School and Faculty of Science and Informatics, University of Szeged, Szeged, Hungary Department of Medical Physics and Informatics, Albert Szent-Györgyi Medical School and Faculty of Science and Informatics, University of Szeged, Szeged, Hungary Export Date: 21 April 2023 CODEN: JONRA Correspondence Address: Farkas, E.; Department of Cell Biology and Molecular Medicine, Somogyi u. 4, H-6720, Hungary; email: eszter.farkas@hcemm.eu LA - English DB - MTMT ER - TY - JOUR AU - Törteli, Anna AU - Tóth, Réka AU - Berger, Sarah AU - Samardzic, Sarah AU - Bari, Ferenc AU - Menyhárt, Ákos AU - Farkas, Eszter TI - Spreading depolarization causes reperfusion failure after cerebral ischemia JF - JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM J2 - J CEREBR BLOOD F MET VL - 43 PY - 2023 IS - 5 SP - 655 EP - 664 PG - 10 SN - 0271-678X DO - 10.1177/0271678X231153745 UR - https://m2.mtmt.hu/api/publication/33602905 ID - 33602905 N1 - Hungarian Centre of Excellence for Molecular Medicine, University of Szeged, Cerebral Blood Flow and Metabolism Research Group, Szeged, Hungary Department of Cell Biology and Molecular Medicine, Albert Szent-Györgyi Medical School and Faculty of Science and Informatics, University of Szeged, Szeged, Hungary Department of Medical Physics and Informatics, Albert Szent-Györgyi Medical School, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary Export Date: 21 April 2023 CODEN: JCBMD Correspondence Address: Menyhárt, Á.; Hungarian Centre of Excellence for Molecular Medicine, Hungary; email: menyhart.akos@med.u-szeged.hu Correspondence Address: Farkas, E.; Hungarian Centre of Excellence for Molecular Medicine, Hungary; email: eszter.farkas@hcemm.eu AB - Despite successful recanalization, reperfusion failure associated with poor neurological outcomes develops in half of treated stroke patients. We explore here whether spreading depolarization (SD) is a predictor of reperfusion failure. Global forebrain ischemia/reperfusion was induced in male and female C57BL/6 mice (n = 57). SD and cerebral blood flow (CBF) changes were visualized with transcranial intrinsic optical signal and laser speckle contrast imaging. To block SD, MK801 was applied (n = 26). Neurological deficit, circle of Willis (CoW) anatomy and neuronal injury were evaluated 24 hours later. SD emerged after ischemia onset in one or both hemispheres under a perfusion threshold (CBF drop to 21.1 ± 4.6 vs. 33.6 ± 4.4%, SD vs. no SD). The failure of later reperfusion (44.4 ± 12.5%) was invariably linked to previous SD. In contrast, reperfusion was adequate (98.9 ± 7.4%) in hemispheres devoid of SD. Absence of the P1 segment of the posterior cerebral artery in the CoW favored SD occurrence and reperfusion failure. SD occurrence and reperfusion failure were associated with poor neurologic function, and neuronal necrosis 24 hours after ischemia. The inhibition of SD significantly improved reperfusion. SD occurrence during ischemia impairs later reperfusion, prognosticating poor neurological outcomes. The increased likelihood of SD occurrence is predicted by inadequate collaterals. LA - English DB - MTMT ER - TY - JOUR AU - Törteli, Anna AU - Tóth, Réka AU - Sarah, Samardzic AU - Sarah, Berger AU - Bari, Ferenc AU - Farkas, Eszter AU - Menyhárt, Ákos TI - The inhibition of spreading depolarization may prevent reperfusion failure after ischemic stroke JF - JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM J2 - J CEREBR BLOOD F MET VL - 42 PY - 2022 IS - IS SP - 151 EP - 151 PG - 1 SN - 0271-678X UR - https://m2.mtmt.hu/api/publication/34162729 ID - 34162729 AB - Background: Despite successful recanalization therapies (i.e., systemic thrombolysis, endovascular thrombectomy), insufficient reperfusion is often observed in ischemic stroke care. In fact, the efficiency of reperfusion might be determined by spreading depolarizations (SDs), secondary pathological events that trigger perfusion deficit and lesion maturation. Aim: Here, we aimed to improve reperfusion by the pharmacological blockade of SDs. Method: Male (n = 12) C57BL/6 mice were anesthetized with isoflurane (0.6–0.9%). A baseline of 10 min was followed by a transient (45 min) bilateral common carotid artery occlusion (2VO) and a subsequent 60 min reperfusion. Cerebral blood flow (CBF) variations were captured using green light reflectance and laser speckle contrast imaging. The irreversible NMDA receptor antagonist MK801 was applied intraperitoneally (0.3 mg/kg). Post stroke neurological deficit was classified after 24 hours on a Composite Garcia Neuroscore scale (0–21). Results/Conclusions: Low CBF early under ischemia favored SD evolution (SD vs. no SD; <25% vs. >35%). MK801 treatment reduced SD incidence (6/6 vs. 10/6 SD/animal; MK801 vs. Control) and the size of the cortical area invaded by SD (67.12 ± 11.3 vs. 85.32 ± 14.32%; MK801 vs. Control). In concert, MK801 improved the level of reperfusion (92.1 ± 12.37 vs. 54.5 ± 33.2%; MK801 vs. Control) and its slope (2.33 ± 0.78 vs. 0.78 ± 0.12%/s; MK801 vs. Control). Accordingly, MK801 treatment was associated with higher neuroscore values (18.33 ± 1.08 vs. 16.33 ± 0.57; MK801 vs. Control). Our data demonstrate that SD inhibition improves reperfusion after ischemic stroke. We propose that the pharmacological inhibition of SDs may facilitate sufficient reperfusion after recanalization in ischemic stroke care. LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Réka AU - Törteli, Anna AU - Sarah, Berger AU - Sarah, Samardzic AU - Bari, Ferenc AU - Menyhárt, Ákos AU - Farkas, Eszter TI - Spreading depolarization is implicated in insufficient reperfusion in the ischemic mouse cerebral cortex JF - JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM J2 - J CEREBR BLOOD F MET VL - 42 PY - 2022 IS - IS SP - 150 EP - 151 PG - 2 SN - 0271-678X UR - https://m2.mtmt.hu/api/publication/34162683 ID - 34162683 AB - Background: Despite successful recanalization, reperfusion failure is often observed in ischemic stroke care. In fact, the efficiency of reperfusion might be determined by secondary pathophysiological events that evolve due to reduced collateral circulation in the ischemic brain. As the major principle of secondary brain injury, spreading depolarization (SD) triggers vasoconstriction and lesion maturation. Aim: We hypothesize that incomplete collateral anastomoses predict SD evolution under ischemia, which establishes reperfusion failure despite successful recanalization. Method: Male C57BL/6 mice (n = 15) were anesthetized with isoflurane (0.6–0.9%). After 10 min of baseline, transient (45 min) bilateral carotid artery occlusion (2VO) was followed by 60 min reperfusion. Intrinsic optical and cerebral blood flow (CBF) changes were captured using green light reflectance and laser speckle contrast imaging. Anatomical features of the circle of Willis were examined after carbon black ink perfusion. Results/Conclusions: Low CBF (<25%) during ischemia favored SD evolution (SD vs. no SD; <25% vs. >35%). SDs occurred in both hemispheres (bilateral) in 33%, in one hemisphere (unilateral) in 54% and in neither hemisphere (no-SD) in 13% of mice. In concert, reperfusion was insufficient in 33%, partial in 54%, and complete in 13% of the animals (28.74 ± 9.89 vs. 55.12 ± 13 vs. 96.88 ± 5.33% CBF, bilateral vs. unilateral vs. no SD). Accordingly, absence of the P1 segment of the posterior cerebral artery (PCA) was detected at the hemispheres affected by SD. Reperfusion failure is usually attributed to out-of-time intervention or localization of the infarct. We demonstrate that decreased collateral circulation fosters SD occurrence and insufficient reperfusion in ischemic stroke. LA - English DB - MTMT ER - TY - BOOK ED - Bari, Ferenc ED - Rárosi, Ferenc ED - Szűcs, Mónika TI - Az egészségügyi informatika COVID előtt és COVID után - A XXXV. Neumann Kollokvium konferencia kiadványa PB - Neumann János Számítógép-tudományi Társaság CY - Szeged PY - 2022 SN - 9786155036224 DO - 10.5281/zenodo.7376144 UR - https://m2.mtmt.hu/api/publication/33267358 ID - 33267358 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Abdelghafour, Mohamed M. AU - Orbán, Ágoston AU - Imre-Deák, Ágota AU - Lamch, Łukasz AU - Nagyné Frank, Éva AU - Nagy, Roland AU - Ziegenheim, Szilveszter AU - Sipos, Pál Miklós AU - Farkas, Eszter AU - Bari, Ferenc AU - Janovák, László TI - Biocompatible poly(ethylene succinate) polyester with molecular weight dependent drug release properties JF - INTERNATIONAL JOURNAL OF PHARMACEUTICS J2 - INT J PHARM VL - 618 PY - 2022 PG - 11 SN - 0378-5173 DO - 10.1016/j.ijpharm.2022.121653 UR - https://m2.mtmt.hu/api/publication/32741246 ID - 32741246 N1 - Department of Physical Chemistry and Materials Science, University of Szeged, H-6720, Rerrich Béla tér 1, Szeged, Hungary Department of Chemistry, Faculty of Science, Zagazig University, Zagazig, 44519, Egypt Department of Organic and Pharmaceutical Technology, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, Wrocław, 50-370, Poland Department of Organic Chemistry, University of Szeged, Dóm tér 8, Szeged, H-6720, Hungary Department of MOL Department of Hydrocarbon and Coal Processing, Faculty of Engineering, University of Pannonia, Egyetem Str. 10, Veszprém, H-8200, Hungary Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, Szeged, H-6720, Hungary Department of Medical Physics and Informatics, Faculty of Medicine & Faculty of Science and Informatics, University of Szeged, Korányi Fasor 9, Szeged, H-6720, Hungary HCEMM-USZ Cerebral Blood Flow and Metabolism Research Group, University of Szeged, Dugonics Square 13, Szeged, H-6720, Hungary Department of Cell Biology and Molecular Medicine, Faculty of Science and Informatics & Faculty of Medicine, University of Szeged, Somogyi Str. 4, Szeged, H-6720, Hungary Export Date: 13 September 2022 CODEN: IJPHD Correspondence Address: Janovák, L.; Department of Physical Chemistry and Materials Science, H-6720, Rerrich Béla tér 1, Hungary; email: janovakl@chem.u-szeged.hu LA - English DB - MTMT ER - TY - JOUR AU - Menyhárt, Ákos AU - Varga, Dániel Péter AU - M.Tóth, Orsolya AU - Makra, Péter AU - Bari, Ferenc AU - Farkas, Eszter TI - Transient Hypoperfusion to Ischemic/Anoxic Spreading Depolarization is Related to Autoregulatory Failure in the Rat Cerebral Cortex JF - NEUROCRITICAL CARE J2 - NEUROCRIT CARE VL - 37 PY - 2022 IS - Suppl. 1 SP - 112 EP - 122 PG - 11 SN - 1541-6933 DO - 10.1007/s12028-021-01393-z UR - https://m2.mtmt.hu/api/publication/32585588 ID - 32585588 N1 - Department of Medical Physics and Informatics, Faculty of Science and Informatics, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary Cerebral Blood Flow and Metabolism Research Group, Hungarian Centre of Excellence for Molecular Medicine, University of Szeged, Szeged, Hungary Department of Cell Biology and Molecular Medicine, Faculty of Science and Informatics, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary Institute for Stroke and Dementia Research, University Hospital, Ludwig Maximilians University Munich, Munich, Germany Cited By :3 Export Date: 21 April 2023 Correspondence Address: Farkas, E.; Cerebral Blood Flow and Metabolism Research Group, Hungary; email: eszter.farkas@hcemm.eu LA - English DB - MTMT ER -