@article{StrekalovaPavlovTrofimovetal.2022,
  author    = {Strekalova, Tatyana and Pavlov, Dmitrii and Trofimov, Alexander and Anthony, Daniel C. and Svistunov, Andrei and Proshin, Andrey and Umriukhin, Aleksei and Lyundup, Alexei and Lesch, Klaus-Peter and Cespuglio, Raymond},
  title     = {Hippocampal over-expression of cyclooxygenase-2 (COX-2) is associated with susceptibility to stress-induced anhedonia in mice},
  series = {International Journal of Molecular Sciences},
  volume    = {23},
  journal   = {International Journal of Molecular Sciences},
  number    = {4},
  issn      = {1422-0067},
  doi       = {10.3390/ijms23042061},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284056},
  year      = {2022},
  abstract  = {The phenomenon of individual variability in susceptibility/resilience to stress and depression, in which the hippocampus plays a pivotal role, is attracting increasing attention. We investigated the potential role of hippocampal cyclooxygenase-2 (COX-2), which regulates plasticity, neuroimmune function, and stress responses that are all linked to this risk dichotomy. We used a four-week-long chronic mild stress (CMS) paradigm, in which mice could be stratified according to their susceptibility/resilience to anhedonia, a key feature of depression, to investigate hippocampal expression of COX-2, a marker of microglial activation Iba-1, and the proliferation marker Ki67. Rat exposure, social defeat, restraints, and tail suspension were used as stressors. We compared the effects of treatment with either the selective COX-2 inhibitor celecoxib (30 mg/kg/day) or citalopram (15 mg/kg/day). For the celecoxib and vehicle-treated mice, the Porsolt test was used. Anhedonic (susceptible) but not non-anhedonic (resilient) animals exhibited elevated COX-2 mRNA levels, increased numbers of COX-2 and Iba-1-positive cells in the dentate gyrus and the CA1 area, and decreased numbers of Ki67-positive cells in the subgranular zone of the hippocampus. Drug treatment decreased the percentage of anhedonic mice, normalized swimming activity, reduced behavioral despair, and improved conditioned fear memory. Hippocampal over-expression of COX-2 is associated with susceptibility to stress-induced anhedonia, and its pharmacological inhibition with celecoxib has antidepressant effects that are similar in size to those of citalopram.},
  language  = {en}
}
@article{WinterAndelovicKampfetal.2021,
  author    = {Winter, Patrick M. and Andelovic, Kristina and Kampf, Thomas and Hansmann, Jan and Jakob, Peter Michael and Bauer, Wolfgang Rudolf and Zernecke, Alma and Herold, Volker},
  title     = {Simultaneous measurements of 3D wall shear stress and pulse wave velocity in the murine aortic arch},
  series = {Journal of Cardiovascular Magnetic Resonance},
  volume    = {23},
  journal   = {Journal of Cardiovascular Magnetic Resonance},
  number    = {1},
  doi       = {10.1186/s12968-021-00725-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259152},
  pages     = {34},
  year      = {2021},
  abstract  = {Purpose Wall shear stress (WSS) and pulse wave velocity (PWV) are important parameters to characterize blood flow in the vessel wall. Their quantification with flow-sensitive phase-contrast (PC) cardiovascular magnetic resonance (CMR), however, is time-consuming. Furthermore, the measurement of WSS requires high spatial resolution, whereas high temporal resolution is necessary for PWV measurements. For these reasons, PWV and WSS are challenging to measure in one CMR session, making it difficult to directly compare these parameters. By using a retrospective approach with a flexible reconstruction framework, we here aimed to simultaneously assess both PWV and WSS in the murine aortic arch from the same 4D flow measurement. Methods Flow was measured in the aortic arch of 18-week-old wildtype (n = 5) and ApoE\(^{-/-}\) mice (n = 5) with a self-navigated radial 4D-PC-CMR sequence. Retrospective data analysis was used to reconstruct the same dataset either at low spatial and high temporal resolution (PWV analysis) or high spatial and low temporal resolution (WSS analysis). To assess WSS, the aortic lumen was labeled by semi-automatically segmenting the reconstruction with high spatial resolution. WSS was determined from the spatial velocity gradients at the lumen surface. For calculation of the PWV, segmentation data was interpolated along the temporal dimension. Subsequently, PWV was quantified from the through-plane flow data using the multiple-points transit-time method. Reconstructions with varying frame rates and spatial resolutions were performed to investigate the influence of spatiotemporal resolution on the PWV and WSS quantification. Results 4D flow measurements were conducted in an acquisition time of only 35 min. Increased peak flow and peak WSS values and lower errors in PWV estimation were observed in the reconstructions with high temporal resolution. Aortic PWV was significantly increased in ApoE\(^{-/-}\) mice compared to the control group (1.7 ± 0.2 versus 2.6 ± 0.2 m/s, p < 0.001). Mean WSS magnitude values averaged over the aortic arch were (1.17 ± 0.07) N/m\(^2\) in wildtype mice and (1.27 ± 0.10) N/m\(^2\) in ApoE\(^{-/-}\) mice. Conclusion The post processing algorithm using the flexible reconstruction framework developed in this study permitted quantification of global PWV and 3D-WSS in a single acquisition. The possibility to assess both parameters in only 35 min will markedly improve the analyses and information content of in vivo measurements.},
  language  = {en}
}
@article{FischhaberFaberBakircietal.2021,
  author    = {Fischhaber, Natalie and Faber, Jessica and Bakirci, Ezgi and Dalton, Paul D. and Budday, Silvia and Villmann, Carmen and Schaefer, Natascha},
  title     = {Spinal Cord Neuronal Network Formation in a 3D Printed Reinforced Matrix-A Model System to Study Disease Mechanisms},
  series = {Advanced Healthcare Materials},
  volume    = {10},
  journal   = {Advanced Healthcare Materials},
  number    = {19},
  doi       = {10.1002/adhm.202100830},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-256353},
  year      = {2021},
  abstract  = {3D cell cultures allow a better mimicry of the biological and mechanical environment of cells in vivo compared to 2D cultures. However, 3D cell cultures have been challenging for ultrasoft tissues such as the brain. The present study uses a microfiber reinforcement approach combining mouse primary spinal cord neurons in Matrigel with melt electrowritten (MEW) frames. Within these 3D constructs, neuronal network development is followed for 21 days in vitro. To evaluate neuronal development in 3D constructs, the maturation of inhibitory glycinergic synapses is analyzed using protein expression, the complex mechanical properties by assessing nonlinearity, conditioning, and stress relaxation, and calcium imaging as readouts. Following adaptation to the 3D matrix-frame, mature inhibitory synapse formation is faster than in 2D demonstrated by a steep increase in glycine receptor expression between days 3 and 10. The 3D expression pattern of marker proteins at the inhibitory synapse and the mechanical properties resemble the situation in native spinal cord tissue. Moreover, 3D spinal cord neuronal networks exhibit intensive neuronal activity after 14 days in culture. The spinal cord cell culture model using ultrasoft matrix reinforced by MEW fibers provides a promising tool to study and understand biomechanical mechanisms in health and disease.},
  language  = {en}
}
@article{AndelovicWinterKampfetal.2021,
  author    = {Andelovic, Kristina and Winter, Patrick and Kampf, Thomas and Xu, Anton and Jakob, Peter Michael and Herold, Volker and Bauer, Wolfgang Rudolf and Zernecke, Alma},
  title     = {2D Projection Maps of WSS and OSI Reveal Distinct Spatiotemporal Changes in Hemodynamics in the Murine Aorta during Ageing and Atherosclerosis},
  series = {Biomedicines},
  volume    = {9},
  journal   = {Biomedicines},
  number    = {12},
  issn      = {2227-9059},
  doi       = {10.3390/biomedicines9121856},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252164},
  year      = {2021},
  abstract  = {Growth, ageing and atherosclerotic plaque development alter the biomechanical forces acting on the vessel wall. However, monitoring the detailed local changes in wall shear stress (WSS) at distinct sites of the murine aortic arch over time has been challenging. Here, we studied the temporal and spatial changes in flow, WSS, oscillatory shear index (OSI) and elastic properties of healthy wildtype (WT, n = 5) and atherosclerotic apolipoprotein E-deficient (Apoe\(^{-/-}\), n = 6) mice during ageing and atherosclerosis using high-resolution 4D flow magnetic resonance imaging (MRI). Spatially resolved 2D projection maps of WSS and OSI of the complete aortic arch were generated, allowing the pixel-wise statistical analysis of inter- and intragroup hemodynamic changes over time and local correlations between WSS, pulse wave velocity (PWV), plaque and vessel wall characteristics. The study revealed converse differences of local hemodynamic profiles in healthy WT and atherosclerotic Apoe\(^{-/-}\) mice, and we identified the circumferential WSS as potential marker of plaque size and composition in advanced atherosclerosis and the radial strain as a potential marker for vascular elasticity. Two-dimensional (2D) projection maps of WSS and OSI, including statistical analysis provide a powerful tool to monitor local aortic hemodynamics during ageing and atherosclerosis. The correlation of spatially resolved hemodynamics and plaque characteristics could significantly improve our understanding of the impact of hemodynamics on atherosclerosis, which may be key to understand plaque progression towards vulnerability.},
  language  = {en}
}
@article{KoenigerBellMifkaetal.2021,
  author    = {Koeniger, Tobias and Bell, Luisa and Mifka, Anika and Enders, Michael and Hautmann, Valentin and Mekala, Subba Rao and Kirchner, Philipp and Ekici, Arif B. and Schulz, Christian and W{\"o}rsd{\"o}rfer, Philipp and Mencl, Stine and Kleinschnitz, Christoph and Erg{\"u}n, S{\"u}leyman and Kuerten, Stefanie},
  title     = {Bone marrow-derived myeloid progenitors in the leptomeninges of adult mice},
  series = {Stem Cells},
  volume    = {39},
  journal   = {Stem Cells},
  number    = {2},
  doi       = {10.1002/stem.3311},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224452},
  pages     = {227 -- 239},
  year      = {2021},
  abstract  = {Although the bone marrow contains most hematopoietic activity during adulthood, hematopoietic stem and progenitor cells can be recovered from various extramedullary sites. Cells with hematopoietic progenitor properties have even been reported in the adult brain under steady-state conditions, but their nature and localization remain insufficiently defined. Here, we describe a heterogeneous population of myeloid progenitors in the leptomeninges of adult C57BL/6 mice. This cell pool included common myeloid, granulocyte/macrophage, and megakaryocyte/erythrocyte progenitors. Accordingly, it gave rise to all major myelo-erythroid lineages in clonogenic culture assays. Brain-associated progenitors persisted after tissue perfusion and were partially inaccessible to intravenous antibodies, suggesting their localization behind continuous blood vessel endothelium such as the blood-arachnoid barrier. Flt3\(^{Cre}\) lineage tracing and bone marrow transplantation showed that the precursors were derived from adult hematopoietic stem cells and were most likely continuously replaced via cell trafficking. Importantly, their occurrence was tied to the immunologic state of the central nervous system (CNS) and was diminished in the context of neuroinflammation and ischemic stroke. Our findings confirm the presence of myeloid progenitors at the meningeal border of the brain and lay the foundation to unravel their possible functions in CNS surveillance and local immune cell production.},
  language  = {en}
}
@article{SchmidSteinleinWinking2016,
  author    = {Schmid, Michael and Steinlein, Claus and Winking, Heinz},
  title     = {Multicolor Spectral Analyses of Mitotic and Meiotic Mouse Chromosomes Involved in Multiple Robertsonian Translocations. I. The CD/Cremona Hybrid Strain},
  series = {Cytogenetic and Genome Research},
  volume    = {147},
  journal   = {Cytogenetic and Genome Research},
  number    = {4},
  issn      = {1424-8581},
  doi       = {10.1159/000444597},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-199013},
  pages     = {253-259},
  year      = {2016},
  abstract  = {Multicolor spectral analysis (spectral karyotyping) was applied to mitotic and male diakinetic chromosomes of hybrid mice carrying a unique system of 18 autosomal Robertsonian translocation chromosomes with alternating arm homologies. Only the autosomes 19 and the XY sex chromosomes are excluded from these Robertsonian translocations. The translocations, previously identified by conventional banding analyses, could be verified by spectral karyotyping. Besides the Robertsonian translocations, no other interchromosomal rearrangements were detected. In diakineses of male meiosis, the 18 metacentric Robertsonian translocation chromosomes form a very large meiotic 'superring'. The predictable, specific order of the chromosomes along this 'superring' was completely confirmed by multicolor spectral analysis. In the majority of diakineses analyzed, the free autosomal bivalent 19 and the XY sex bivalent form a conspicuous complex which tightly associates with the 12;14 Robertsonian translocation chromosome in the 'superring'.},
  language  = {en}
}
@article{BalkenholKaltdorfMammadovaBachetal.2020,
  author    = {Balkenhol, Johannes and Kaltdorf, Kristin V. and Mammadova-Bach, Elmina and Braun, Attila and Nieswandt, Bernhard and Dittrich, Marcus and Dandekar, Thomas},
  title     = {Comparison of the central human and mouse platelet signaling cascade by systems biological analysis},
  series = {BMC Genomics},
  volume    = {21},
  journal   = {BMC Genomics},
  doi       = {10.1186/s12864-020-07215-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230377},
  year      = {2020},
  abstract  = {Background Understanding the molecular mechanisms of platelet activation and aggregation is of high interest for basic and clinical hemostasis and thrombosis research. The central platelet protein interaction network is involved in major responses to exogenous factors. This is defined by systemsbiological pathway analysis as the central regulating signaling cascade of platelets (CC). Results The CC is systematically compared here between mouse and human and major differences were found. Genetic differences were analysed comparing orthologous human and mouse genes. We next analyzed different expression levels of mRNAs. Considering 4 mouse and 7 human high-quality proteome data sets, we identified then those major mRNA expression differences (81\%) which were supported by proteome data. CC is conserved regarding genetic completeness, but we observed major differences in mRNA and protein levels between both species. Looking at central interactors, human PLCB2, MMP9, BDNF, ITPR3 and SLC25A6 (always Entrez notation) show absence in all murine datasets. CC interactors GNG12, PRKCE and ADCY9 occur only in mice. Looking at the common proteins, TLN1, CALM3, PRKCB, APP, SOD2 and TIMP1 are higher abundant in human, whereas RASGRP2, ITGB2, MYL9, EIF4EBP1, ADAM17, ARRB2, CD9 and ZYX are higher abundant in mouse. Pivotal kinase SRC shows different regulation on mRNA and protein level as well as ADP receptor P2RY12. Conclusions Our results highlight species-specific differences in platelet signaling and points of specific fine-tuning in human platelets as well as murine-specific signaling differences.},
  language  = {en}
}
@article{HoffmannJanssenKannoetal.2020,
  author    = {Hoffmann, Jan V. and Janssen, Jan P. and Kanno, Takayuki and Shibutani, Takayuki and Onoguchi, Masahisa and Lapa, Constantin and Grunz, Jan-Peter and Buck, Andreas K. and Higuchi, Takahiro},
  title     = {Performance evaluation of fifth-generation ultra-high-resolution SPECT system with two stationary detectors and multi-pinhole imaging},
  series = {EJNMMI Physics},
  volume    = {7},
  journal   = {EJNMMI Physics},
  doi       = {10.1186/s40658-020-00335-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230361},
  year      = {2020},
  abstract  = {Background Small-animal single-photon emission computed tomography (SPECT) systems with multi-pinhole collimation and large stationary detectors have advantages compared to systems with moving small detectors. These systems benefit from less labour-intensive maintenance and quality control as fewer prone parts are moving, higher accuracy for focused scans and maintaining high resolution with increased sensitivity due to focused pinholes on the field of view. This study aims to investigate the performance of a novel ultra-high-resolution scanner with two-detector configuration (U-SPECT5-E) and to compare its image quality to a conventional micro-SPECT system with three stationary detectors (U-SPECT\(^+\)). Methods The new U-SPECT5-E with two stationary detectors was used for acquiring data with \(^{99m}\)Tc-filled point source, hot-rod and uniformity phantoms to analyse sensitivity, spatial resolution, uniformity and contrast-to-noise ratio (CNR). Three dedicated multi-pinhole mouse collimators with 75 pinholes each and 0.25-, 0.60- and 1.00-mm pinholes for extra ultra-high resolution (XUHR-M), general-purpose (GP-M) and ultra-high sensitivity (UHS-M) imaging were examined. For CNR analysis, four different activity ranges representing low- and high-count settings were investigated for all three collimators. The experiments for the performance assessment were repeated with the same GP-M collimator in the three-detector U-SPECT\(^+\) for comparison. Results Peak sensitivity was 237 cps/MBq (XUHR-M), 847 cps/MBq (GP-M), 2054 cps/MBq (UHS-M) for U-SPECT5-E and 1710 cps/MBq (GP-M) for U-SPECT\(^+\). In the visually analysed sections of the reconstructed mini Derenzo phantoms, rods as small as 0.35 mm (XUHR-M), 0.50 mm (GP-M) for the two-detector as well as the three-detector SPECT and 0.75 mm (UHS-M) were resolved. Uniformity for maximum resolution recorded 40.7\% (XUHR-M), 29.1\% (GP-M, U-SPECT5-E), 16.3\% (GP-M, U-SPECT\(^+\)) and 23.0\% (UHS-M), respectively. UHS-M reached highest CNR values for low-count images; for rods smaller than 0.45 mm, acceptable CNR was only achieved by XUHR-M. GP-M was superior for imaging rods sized from 0.60 to 1.50 mm for intermediate activity concentrations. U-SPECT5-E and U-SPECT+ both provided comparable CNR. Conclusions While uniformity and sensitivity are negatively affected by the absence of a third detector, the investigated U-SPECT5-E system with two stationary detectors delivers excellent spatial resolution and CNR comparable to the performance of an established three-detector-setup.},
  language  = {en}
}
@article{RiedlKampfHeroldetal.2020,
  author    = {Riedl, Katharina A. and Kampf, Thomas and Herold, Volker and Behr, Volker C. and Bauer, Wolfgang R.},
  title     = {Wall shear stress analysis using 17.6 Tesla MRI: A longitudinal study in ApoE\(^{-/-}\)mice with histological analysis},
  series = {PLoS One},
  volume    = {15},
  journal   = {PLoS One},
  number    = {8},
  doi       = {10.1371/journal.pone.0238112},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229318},
  year      = {2020},
  abstract  = {This longitudinal study was performed to evaluate the feasibility of detecting the interaction between wall shear stress (WSS) and plaque development. 20 ApoE\(^{-/-}\)mice were separated in 12 mice with Western Diet and 8 mice with Chow Diet. Magnetic resonance (MR) scans at 17.6 Tesla and histological analysis were performed after one week, eight and twelve weeks. Allin vivoMR measurements were acquired using a flow sensitive phase contrast method for determining vectorial flow. Histological sections were stained with Hematoxylin and Eosin, Elastica van Gieson and CD68 staining. Data analysis was performed using Ensight and a Matlab-based "Flow Tool". The body weight of ApoE\(^{-/-}\)mice increased significantly over 12 weeks. WSS values increased in the Western Diet group over the time period; in contrast, in the Chow Diet group the values decreased from the first to the second measurement point. Western Diet mice showed small plaque formations with elastin fragmentations after 8 weeks and big plaque formations after 12 weeks; Chow Diet mice showed a few elastin fragmentations after 8 weeks and small plaque formations after 12 weeks. Favored by high-fat diet, plaque formation results in higher values of WSS. With wall shear stress being a known predictor for atherosclerotic plaque development, ultra highfield MRI can serve as a tool for studying the causes and beginnings of atherosclerosis.},
  language  = {en}
}
@article{GerullBrodehl2020,
  author    = {Gerull, Brenda and Brodehl, Andreas},
  title     = {Genetic Animal Models for Arrhythmogenic Cardiomyopathy},
  series = {Frontiers in Physiology},
  volume    = {11},
  journal   = {Frontiers in Physiology},
  number    = {264},
  issn      = {1664-042X},
  doi       = {10.3389/fphys.2020.00624},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-206903},
  year      = {2020},
  abstract  = {Arrhythmogenic cardiomyopathy has been clinically defined since the 1980s and causes right or biventricular cardiomyopathy associated with ventricular arrhythmia. Although it is a rare cardiac disease, it is responsible for a significant proportion of sudden cardiac deaths, especially in athletes. The majority of patients with arrhythmogenic cardiomyopathy carry one or more genetic variants in desmosomal genes. In the 1990s, several knockout mouse models of genes encoding for desmosomal proteins involved in cell-cell adhesion revealed for the first time embryonic lethality due to cardiac defects. Influenced by these initial discoveries in mice, arrhythmogenic cardiomyopathy received an increasing interest in human cardiovascular genetics, leading to the discovery of mutations initially in desmosomal genes and later on in more than 25 different genes. Of note, even in the clinic, routine genetic diagnostics are important for risk prediction of patients and their relatives with arrhythmogenic cardiomyopathy. Based on improvements in genetic animal engineering, different transgenic, knock-in, or cardiac-specific knockout animal models for desmosomal and nondesmosomal proteins have been generated, leading to important discoveries in this field. Here, we present an overview about the existing animal models of arrhythmogenic cardiomyopathy with a focus on the underlying pathomechanism and its importance for understanding of this disease. Prospectively, novel mechanistic insights gained from the whole animal, organ, tissue, cellular, and molecular levels will lead to the development of efficient personalized therapies for treatment of arrhythmogenic cardiomyopathy.},
  language  = {en}
}