Research Interests:
Obesity is characterized by immoderate fat accumulation leading to an elevated risk of neurodegenerative disorders, along with a host of metabolic disturbances. Chronic neuroinflammation is a main factor linking obesity and the propensity... more
Obesity is characterized by immoderate fat accumulation leading to an elevated risk of neurodegenerative disorders, along with a host of metabolic disturbances. Chronic neuroinflammation is a main factor linking obesity and the propensity for neurodegenerative disorders. To determine the cerebrometabolic effects of diet-induced obesity (DIO) in female mice fed a long-term (24 weeks) high-fat diet (HFD, 60% fat) compared to a group on a control diet (CD, 20% fat), we used in vivo PET imaging with the radiotracer [18F]FDG as a marker for brain glucose metabolism. In addition, we determined the effects of DIO on cerebral neuroinflammation using translocator protein 18 kDa (TSPO)-sensitive PET imaging with [18F]GE-180. Finally, we performed complementary post mortem histological and biochemical analyses of TSPO and further microglial (Iba1, TMEM119) and astroglial (GFAP) markers as well as cerebral expression analyses of cytokines (e.g., Interleukin (IL)-1β). We showed the development o...
Research Interests:
These abstracts are licensed under a Creative Commons Attribution-NonCommercial-No Derivatives 4.0 International License. Go to http://iovs.arvojournals.org/ to access the versions of record. 239 Embryology and morphogenesis of ocular... more
These abstracts are licensed under a Creative Commons Attribution-NonCommercial-No Derivatives 4.0 International License. Go to http://iovs.arvojournals.org/ to access the versions of record. 239 Embryology and morphogenesis of ocular structures Monday, May 08, 2017 11:00 AM–12:45 PM Exhibit/Poster Hall Poster Session Program #/Board # Range: 1723–1735/A0201–A0213 Organizing Section: Anatomy and Pathology/Oncology
Novel therapeutic strategies aiming at improving the healing process after an acute myocardial infarction are currently under intense investigation. The mouse model plays a central role for deciphering the underlying mechanisms on a... more
Novel therapeutic strategies aiming at improving the healing process after an acute myocardial infarction are currently under intense investigation. The mouse model plays a central role for deciphering the underlying mechanisms on a molecular and cellular level. Therefore, we intended to assess in-vivo post-infarct remodeling as comprehensively as possible using an expedient native magnetic resonance imaging (MRI) in the two most prominent infarct models, permanent ligation (PL) of the left anterior descending artery (LAD) versus ischemia reperfusion (I/R). Mice were subjected to either permanent or transient (45 min) occlusion of the LAD. After 3 weeks, examinations were performed with a 7-Tesla small animal MRI system. Data analysis was performed with the freely available software Segment. PL resulted in a massive dilation of the left ventricle, accompanied by hypertrophy of the non-infarcted myocardium and a decline of contractile function. These effects were less pronounced foll...
Research Interests:
Research Interests:
Blood glucose concentrations of wild type (wt; n = 8) and Apolipoprotein E-deficient (ApoE–/–; n = 8) mice were measured directly before (A) and after (B) [18F]FDG-PET/CT scans. Values are given as mean ± SD
Research Interests:
Background Strong line of evidence suggests that the increased risk to develop AD may at least be partly mediated by cholesterol metabolism. A key regulator of cholesterol transport is the Apolipoprotein E4 (ApoE4), which plays a... more
Background Strong line of evidence suggests that the increased risk to develop AD may at least be partly mediated by cholesterol metabolism. A key regulator of cholesterol transport is the Apolipoprotein E4 (ApoE4), which plays a fundamental role in neuronal maintenance and repair. Impaired function of ApoE4 may contribute to altered cerebral metabolism leading to higher susceptibility to neurodegeneration. Methods To determine a possible link between ApoE function and alterations in AD in the brain of Apolipoprotein E-deficient mice (ApoE−/−) in a longitudinal manner metabolic and neurochemical parameters were analyzed. Cortical metabolism was measured by 2-deoxy-2-[18F]fluoroglucose ([18F]FDG)-PET/CT and proton magnetic resonance spectroscopy (1H-MRS) served to record neurochemical status. Results By using [18F]FDG-PET/CT, we showed that brain metabolism declined significantly stronger with age in ApoE−/− versus wild type (wt) mice. This difference was particularly evident at the ...
Research Interests:
In the present study, a newly introduced bovine cross-linked collagen scaffold (test material) was investigated in vivo in an Achilles tendon defect model and compared to a commercially available porcine collagen scaffold (control... more
In the present study, a newly introduced bovine cross-linked collagen scaffold (test material) was investigated in vivo in an Achilles tendon defect model and compared to a commercially available porcine collagen scaffold (control material). In total, 28 male Sprague Dawley rats (about 400 g) were examined. The defined Achilles tendon defect of 5 mm of the right hind limb was replaced by one of the scaffold materials. After euthanasia, the hind limbs were transected for testing. Biomechanical evaluation was carried out via tensile testing (n = 8 each group, observation time: 28 days). Nonoperated tendons from the bilateral side were used as a control (native tendon, n = 4). For the histological evaluation, 12 animals were sacrificed at 14 and 28 days postoperatively (n = 3 each group and time point). Stained slices (Hematoxylin & Eosin) were evaluated qualitatively in terms of presence of cells and cell migration into scaffolds as well as structure and degradation of the scaffold. A...
Research Interests:
Fragestellung: In Deutschland werden jährlich ca. 350.000 künstliche Hüft- und Knie-Gelenke implantiert. Um die Standzeit zu erhöhen und somit die Revisionsrate zu verringern, werden die Implantate mit Oberflächenbeschichtungen versehen.... more
Fragestellung: In Deutschland werden jährlich ca. 350.000 künstliche Hüft- und Knie-Gelenke implantiert. Um die Standzeit zu erhöhen und somit die Revisionsrate zu verringern, werden die Implantate mit Oberflächenbeschichtungen versehen. Hierbei stehen unterschiedliche Eigenschaften[for full text, please go to the a.m. URL]
Abstract: Background: Numerous studies have shown reduction of periprosthetic bone mineral density (BMD) after hip replacement. The effect on the whole limb, however, is still unexplored. This study’s objective was to analyse the... more
Abstract: Background: Numerous studies have shown reduction of periprosthetic bone mineral density (BMD) after hip replacement. The effect on the whole limb, however, is still unexplored. This study’s objective was to analyse the postoperative development of BMD and muscle strength of the limb after total hip replacement (THR) and to determine links between these parameters. Methods: 55 patients, who underwent THR, were included. Depending on therapeutic indication, either an uncemented stem (Group A, n=30) or a cemented stem (Group B, n=25) has been implanted. In the limbs, the measurement of BMD using DEXA and the maximum isometric muscle strength, detected by a leg press, were undertaken preoperatively and after 3, 6 and 12 months. Results: A total of 12 patients (Group A: n = 6, Group B: n = 6) were excluded due to reasons which were not relevant to the study. So, the results refer to the data of 43 patients. In Group A (uncemented, n = 24), a significant decrease of BMD on the ...
Research Interests:
Fragestellung: Die Behandlung groser, segmentaler Knochendefekte wird in der Regel mit autogenem, allogenem Knochenmaterial oder Kalziumphosphaten behandelt. Da diese nur begrenzt verfugbar sind und geringe mechanische Eigenschaften... more
Fragestellung: Die Behandlung groser, segmentaler Knochendefekte wird in der Regel mit autogenem, allogenem Knochenmaterial oder Kalziumphosphaten behandelt. Da diese nur begrenzt verfugbar sind und geringe mechanische Eigenschaften aufweisen, stellen sie fur die Versorgung in hochbelasteten[for full text, please go to the a.m. URL]
Research Interests:
The biomechanical evaluation of tendon repair with collagen-based scaffolds in rat model is a common method to determine the functional outcome of the tested material. We introduced a magnetic resonance imaging (MRI) approach to verify... more
The biomechanical evaluation of tendon repair with collagen-based scaffolds in rat model is a common method to determine the functional outcome of the tested material. We introduced a magnetic resonance imaging (MRI) approach to verify the biomechanical test data. In present study different collagen scaffolds for tendon repair were examined. Two collagen test materials: based on bovine stabilized collagen, chemically cross-linked with oriented collagenous fibres (material 1) and based on porcine dermal extracellular matrix, with no cross-linking (material 2) were compared. The animal study was approved by the local review board. Surgery was performed on male Sprague-Dawley rats with a body weight of 400 ± 19 g. Each rat underwent a 5 mm transection of the right Achilles tendon. The M. plantaris tendon was removed. The remaining tendon ends were re-joined with a 5 mm scaffold of either the material 1 or 2. Each scaffold material was sutured into place with two single stiches (Vicryl ...
Research Interests:
Research Interests:
Ultrahigh-field MRI (UHF-MRI) with an in-plane spatial resolution of less than 100 μm is known as MR microscopy (MRM). MRM provides highly resolved anatomical images and allows quantitative assessment of different tissue types using... more
Ultrahigh-field MRI (UHF-MRI) with an in-plane spatial resolution of less than 100 μm is known as MR microscopy (MRM). MRM provides highly resolved anatomical images and allows quantitative assessment of different tissue types using diffusion-weighted imaging (DWI). The aim of the present study was to evaluate the feasibility of combined in vivo anatomical and quantitative assessment of the developing chicken eye in ovo. Thirty-eight fertilized chicken eggs were examined at 7.1 T (ClinScan, Bruker Biospin, Germany) acquiring a dataset comprising T2-weighted anatomical images, DWI, and diffusion tensor imaging. To reduce motion artifacts, the eggs were moderately cooled before and during MR imaging. Two eggs were imaged daily for the entire developmental period, and 36 eggs were examined pairwise at only one time point of the embryonic period. Development of the eye was anatomically and quantitatively assessed. From the D5 embryonic stage (116-124 h), MRM allowed differentiation betw...
Research Interests:
Ultra-high-field MRI (UHF-MRI) is an outstanding technique for non-invasive and non-destructive imaging of soft tissues and can provide versatile contrasts and high resolution in the µm range. In vivo imaging of the embryonal chick eye... more
Ultra-high-field MRI (UHF-MRI) is an outstanding technique for non-invasive and non-destructive imaging of soft tissues and can provide versatile contrasts and high resolution in the µm range. In vivo imaging of the embryonal chick eye with its filigree anatomical structures imposes these requirements. However, due to the short embryonal development cycle, chicken are a favourite animal model for embryonal research studies. Ultra-high-field MRI allows repeated and longitudinal in ovo investigations on the same embryo. In the present study, the limitations and opportunities of in ovo MR-imaging at 7 T were evaluated and the process of eye growth was described in detail.
Research Interests:
Quantified physical activity is an important parameter for evaluating the risk of the incidence of internal and musculoskeletal disorders. The objective of this study was to evaluate the physical activity of German Soldiers on duty and... more
Quantified physical activity is an important parameter for evaluating the risk of the incidence of internal and musculoskeletal disorders. The objective of this study was to evaluate the physical activity of German Soldiers on duty and during leisure time with regard to individual determinants and to evaluate if factors associated with the risk of the incidence of internal or musculoskeletal disorders are of relevance for physical activity. For this purpose, we conducted activity measurements on 169 subjects. The accelerometer-based activity sensor was worn for 7 consecutive days. The number of steps taken was evaluated as an activity marker.We observed that a high body mass index and a large waist circumference were associated with a low activity level. Women were found to be more active than men, particularly during leisure time. Personnel under 25 years of age were more physically active than those between 25 and 50 years of age. Subjects with underlying musculoskeletal disorders...
Research Interests: Physical Activity, Medicine, Germany, Prospective studies, Humans, and 15 moreFemale, Male, Incidence, Body Mass Index, Health Status, Middle Aged, Adult, Age Factors, Musculoskeletal system, Risk Factors, Military Personnel, Leisure Activities, Motor activity, Musculoskeletal diseases, and Population surveillance
Die Anzahl an notwendigen Revisions-und Wechseloperationen nach Hufttotalendoprothesen steigt kontinuierlich (◘ Abb. 4.1) [1, 2]. Nicht verhindern lasst sich der damit verbundene Knochenverlust im Azetabulum und am Femur [3]. Die... more
Die Anzahl an notwendigen Revisions-und Wechseloperationen nach Hufttotalendoprothesen steigt kontinuierlich (◘ Abb. 4.1) [1, 2]. Nicht verhindern lasst sich der damit verbundene Knochenverlust im Azetabulum und am Femur [3]. Die Wiederherstellung von anatomisch knochernen Verhaltnissen und biomechanisch korrekter Implantatlage ist eine grose Herausforderung, die auf unterschiedliche Weise angegangen werden kann. Fur die Revision des Azetabulums wurden z. B. grose zementfreie Pfannen (sog. Jumbo-Pfannen), Revisionsringe, Stutzschalen und schlussendlich auch Keramiktransplantate verwendet. Diese Methoden stellen zwar die Biomechanik wieder her, fuhren aber nicht zum Wiederherstellen des Knochenlagers. Andere Methoden, wie z. B. Medialisierung der Pfanne oder Implantation in einem hoheren Huftzentrum, konfigurieren eine Situation, die nicht der normalen Biomechanik entspricht. Alternativ konnen Knochendefekte durch modulare porose Metallaugmentationen uberbruckt werden. Als Hauptziel bei der Hufttotalendoprothesenrevisionsoperation sollte neben dem Wiederherstellen der biomechanischen Physiologie immer auch die Wiederherstellung des Knochenlagers im Vordergrund stehen, um im Falle einer weiteren Revision wieder anatomische knocherne Verhaltnisse vorzufinden, die eine neuerliche Implantation ermoglichen. Dieses Kapitel behandelt den Einsatz von Allografts aus der Knochenbank zum Erreichen dieses Ziels.
Research Interests:
This study is designed to examine the feasibility of diffusion-sensitized multishot split-echo rapid acquisition with relaxation enhancement (RARE) for diffusion-weighted ophthalmic imaging free of geometric distortions at 3.0 and 7.0 T... more
This study is designed to examine the feasibility of diffusion-sensitized multishot split-echo rapid acquisition with relaxation enhancement (RARE) for diffusion-weighted ophthalmic imaging free of geometric distortions at 3.0 and 7.0 T in healthy volunteers and patients with intraocular masses. A diffusion-sensitized multishot split-echo RARE (ms-RARE) variant is proposed as an alternative imaging strategy for diffusion-weighted imaging. It is compared with standard single-shot echo planar imaging (EPI) and readout-segmented EPI in terms of geometric distortions in a structure phantom as well as in vivo at 3.0 and 7.0 T. To quantify geometric distortions, center of gravity analysis was carried out. Apparent diffusion coefficient (ADC) mapping in a diffusion phantom was performed to verify the diffusion sensitization within ms-RARE. An in vivo feasibility study in healthy volunteers (n = 10; mean age, 31 ± 7 years; mean body mass index, 22.6 ± 1.7 kg/m) was conducted at 3.0 and 7.0 ...
Research Interests: Magnetic Resonance Imaging, Medicine, Humans, Female, Melanoma, and 13 moreFeasibility Studies, Retinal detachment, Male, Artifacts, Motion, Clinical Sciences, Middle Aged, Image Enhancement, Reproducibility of Results, Sensitivity and Specificity, Pilot Projects, Reference Values, and Diffusion magnetic resonance imaging
Research Interests:
Research Interests:
Quantification of [18F]FDG uptake in the cortex, hippocampus, thalamus, striatum, cerebellum, and brain stem as absolute SUVs of wild type (wt; n = 8) and Apolipoprotein E-deficient (ApoE−/−; n = 8) mice at the age of 15, 29, 41, and 55... more
Quantification of [18F]FDG uptake in the cortex, hippocampus, thalamus, striatum, cerebellum, and brain stem as absolute SUVs of wild type (wt; n = 8) and Apolipoprotein E-deficient (ApoE−/−; n = 8) mice at the age of 15, 29, 41, and 55 weeks. Values are given as mean ± SD; ANOVA for repeated measurements followed by Holm-Sidak comparison test: *p < 0.05 versus 15 weeks
Fragestellung: Die tierexperimentelle Untersuchung der Osseointegration verschiedener Implantatbeschichtungen kann derzeit nur postmortem durch biomechanische Analysen und histomorphometrische Methoden realisiert werden. In der... more
Fragestellung: Die tierexperimentelle Untersuchung der Osseointegration verschiedener Implantatbeschichtungen kann derzeit nur postmortem durch biomechanische Analysen und histomorphometrische Methoden realisiert werden. In der Dentalimplantologie werden Vibrationsverfahren eingesetzt um die Osseointegration[for full text, please go to the a.m. URL]
Research Interests:
Olfactory deficits occur as early non-motor symptoms of idiopathic Parkinson’s disease (PD) in humans. The first central relay of the olfactory pathway, the olfactory bulb (OB), depends, among other things, on an intact, functional... more
Olfactory deficits occur as early non-motor symptoms of idiopathic Parkinson’s disease (PD) in humans. The first central relay of the olfactory pathway, the olfactory bulb (OB), depends, among other things, on an intact, functional crosstalk between dopaminergic interneurons and dopamine receptors (D2/D3R). In rats, hemiparkinsonism (hemi-PD) can be induced by unilateral injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB), disrupting dopaminergic neurons of the substantia nigra pars compacta (SNpc). In a previous study, we showed that subsequent injection of botulinum neurotoxin-A (BoNT-A) into the striatum can reverse most of the pathological motor symptoms and normalize the D2/D3R availability. To determine whether this rat model is suitable to explain olfactory deficits that occur in humans with PD, we examined the availability of D2/D3R by longitudinal [18F]fallypride-PET/CT, the density of tyrosine hydroxylase immunoreactivity in the OB, olfactory per...
Research Interests:
We investigated the influence of syngeneic cardiomyocyte transplantation after myocardial infarction (MI) on the immune response and cardiac function. Methods and Results: We show for the first time that the immune response is altered as... more
We investigated the influence of syngeneic cardiomyocyte transplantation after myocardial infarction (MI) on the immune response and cardiac function. Methods and Results: We show for the first time that the immune response is altered as a result of syngeneic neonatal cardiomyocyte transplantation after MI leading to improved cardiac pump function as observed by magnetic resonance imaging in C57BL/6J mice. Interestingly, there was no improvement in the capillary density as well as infarct area as observed by CD31 and Sirius Red staining, respectively. Flow cytometric analysis revealed a significantly different response of monocyte-derived macrophages and regulatory T cells after cell transplantation. Interestingly, the inhibition of monocyte infiltration accompanied by cardiomyocyte transplantation diminished the positive effect of cell transplantation alone. The number of CD68+ macrophages in the remote area of the heart observed after four weeks was also different between the grou...
Research Interests:
Introduction Implant osseointegration and different surface modifications of different implant coatings can solely be analysed in animal experiments post mortem. In dental implantology, vibration analysis is used to detect the shift in... more
Introduction Implant osseointegration and different surface modifications of different implant coatings can solely be analysed in animal experiments post mortem. In dental implantology, vibration analysis is used to detect the shift in resonance frequency and damping of the implant due to advanced bone ingrowth [Koh, 2009]. However, this method requires a close contact to the implant and excitation using an electrodynamic shaker. In our present work, a novel method with internal excitation of coated implants is investigated using the animal model New Zealand White Rabbit (NZWR).
The present study was designed to provide further insight into the neuromuscular mechanisms that determine the decrease in maximum strength and strength development of the quadriceps muscle with aging. Different neuromuscular tests were... more
The present study was designed to provide further insight into the neuromuscular mechanisms that determine the decrease in maximum strength and strength development of the quadriceps muscle with aging. Different neuromuscular tests were performed in order to assess the neural and muscular changes. The age-related decrease in isometric maximum voluntary torque (iMVT) was accompanied by a decline in voluntary activation and normalized surface electromyographic (EMG) amplitude. Mechanical parameters of explosive voluntary strength were reduced while the corresponding muscle activation remained primarily unchanged. The spinal excitability of the vastus medialis was not different while maximal M wave (Mmax) latency was longer. Contractile properties and lean mass were reduced. In conclusion, the age-related decline in iMVT of the quadriceps muscle might be due to a reduced neural drive and changes in skeletal muscle properties. The decrease in explosive voluntary strength seemed to be mo...
Hydrogels are one of the emerging classes of materials in current research. Besides their numerous applications in the medical sector as a drug delivery system or in tissue replacement, they are also suitable as irrigation components or... more
Hydrogels are one of the emerging classes of materials in current research. Besides their numerous applications in the medical sector as a drug delivery system or in tissue replacement, they are also suitable as irrigation components or as immobilization matrices in catalysis. For optimal application of these compounds, knowledge of the swelling properties and the diffusion mechanisms occurring in the gels is mandatory. This study is focused on hydrogels synthesized by radical polymerization of imidazolium-based ionic liquids. Both the swelling and diffusion behavior of these hydrogels were investigated via gravimetric swelling as well as sorption experiments implemented in water, ethanol, n-heptane, and tetrahydrofuran. In water and ethanol, strong swelling was observed while the transport mechanism deviated from Fickian-type behavior. By varying the counterion and the chain length of the cation, their influences on the processes were observed. The calculation of the diffusion coef...
Research Interests:
Background: Skin cancer is the most frequent cancer worldwide and is divided into non-melanoma skin cancer, including basal cell carcinoma, as well as squamous cell carcinoma (SCC) and malignant melanoma (MM). Methods: This study... more
Background: Skin cancer is the most frequent cancer worldwide and is divided into non-melanoma skin cancer, including basal cell carcinoma, as well as squamous cell carcinoma (SCC) and malignant melanoma (MM). Methods: This study evaluates the effects of cold atmospheric pressure plasma (CAP) on SCC and MM in vivo, employing a comprehensive approach using multimodal imaging techniques. Longitudinal MR and PET/CT imaging were performed to determine the anatomic and metabolic tumour volume over three-weeks in vivo. Additionally, the formation of reactive species after CAP treatment was assessed by non-invasive chemiluminescence imaging of L-012. Histological analysis and immunohistochemical staining for Ki-67, ApopTag®, F4/80, CAE, and CD31, as well as protein expression of PCNA, caspase-3 and cleaved-caspase-3, were performed to study proliferation, apoptosis, inflammation, and angiogenesis in CAP-treated tumours. Results: As the main result, multimodal in vivo imaging revealed a sub...
Research Interests:
Schistosomiasis represents one of the most devastating worm parasitosis in the world. Current diagnostic methods are insufficient to determine the infection grade and the disease related organ damage. We herein investigated whether... more
Schistosomiasis represents one of the most devastating worm parasitosis in the world. Current diagnostic methods are insufficient to determine the infection grade and the disease related organ damage. We herein investigated whether discrimination of infection grade and its correlation to liver damage could be accurately performed by multimodal imaging in a mouse model of Schistosoma mansoni infection. Therefore, groups of uninfected and infected mice underwent MRI and [18F]FDG PET/CT imaging. Anatomical MRI images were used for liver volumetry and for quantification of hepatic granulomas. For PET/CT images a volume of interest based analyses were employed to calculate the [18F]FDG uptake in liver, portal vein, spleen and abdomen. Herein, we demonstrate that the combined use of [18F]FDG-PET/CT and MRI represents an appropriate diagnostic tool for Schistosoma mansoni infection, but fails to discriminate the infection grade and the linked organ damage. Only the splenic [18F]FDG uptake ...
Research Interests:
Caloric restriction (CR) slows the aging process, extends lifespan, and exerts neuroprotective effects. It is widely accepted that CR attenuates β-amyloid (Aβ) neuropathology in models of Alzheimer’s disease (AD) by so-far unknown... more
Caloric restriction (CR) slows the aging process, extends lifespan, and exerts neuroprotective effects. It is widely accepted that CR attenuates β-amyloid (Aβ) neuropathology in models of Alzheimer’s disease (AD) by so-far unknown mechanisms. One promising process induced by CR is autophagy, which is known to degrade aggregated proteins such as amyloids. In addition, autophagy positively regulates glucose uptake and may improve cerebral hypometabolism—a hallmark of AD—and, consequently, neural activity. To evaluate this hypothesis, APPswe/PS1delta9 (tg) mice and their littermates (wild-type, wt) underwent CR for either 16 or 68 weeks. Whereas short-term CR for 16 weeks revealed no noteworthy changes of AD phenotype in tg mice, long-term CR for 68 weeks showed beneficial effects. Thus, cerebral glucose metabolism and neuronal integrity were markedly increased upon 68 weeks CR in tg mice, indicated by an elevated hippocampal fluorodeoxyglucose [18F] ([18F]FDG) uptake and increased N-a...
Research Interests:
Background: To date, there are no effective treatments for Alzheimer’s disease (AD). Thus, a significant need for research of therapies remains. Objective: One promising pharmacological target is the hormone fibroblast growth factor 21... more
Background: To date, there are no effective treatments for Alzheimer’s disease (AD). Thus, a significant need for research of therapies remains. Objective: One promising pharmacological target is the hormone fibroblast growth factor 21 (FGF21), which is thought to be neuroprotective. A clinical candidate for medical use could be the FGF21 analogue LY2405319 (LY), which has a specificity and potency comparable to FGF21. Methods: The present study investigated the potential neuroprotective effect of LY via PPARγ/apoE/abca1 pathway which is known to degrade amyloid-β (Aβ) plaques by using primary glial cells and hippocampal organotypic brain slice cultures (OBSCs) from 30- and 50-week-old transgenic APPswe/PS1dE9 (tg) mice. By LY treatment of 52-week-old tg mice with advanced Aβ deposition, we further aimed to elaborate the effect of LY on AD pathology in vivo. Results: LY application to primary glial cells caused an upregulation of pparγ, apoE, and abca1 mRNA expression and significan...
Research Interests:
Angiogenesis plays a central role in the healing process following acute myocardial infarction. The PET tracer [68Ga]-NODAGA-RGD, which is a ligand for the αvβ3 integrin, has been investigated for imaging angiogenesis in the process of... more
Angiogenesis plays a central role in the healing process following acute myocardial infarction. The PET tracer [68Ga]-NODAGA-RGD, which is a ligand for the αvβ3 integrin, has been investigated for imaging angiogenesis in the process of healing myocardium in both animal and clinical studies. It’s value as a prognostic marker of functional outcome remains unclear. Therefore, the aim of this work was to establish [68Ga]-NODAGA-RGD for imaging angiogenesis in the murine infarct model and evaluate the tracer as a predictor for cardiac remodeling in the context of cardiac stem cell therapy. [68Ga]-NODAGA-RGD PET performed seven days after left anterior descending coronary artery (LAD) occlusion in 129S6 mice showed intense tracer accumulation within the infarct region. The specificity was shown in a sub-group of animals by application of the competitive inhibitor cilengitide prior to tracer injection in a subgroup of animals. Myocardial infarction (MI) significantly reduced cardiac functi...
Research Interests:
Cellular inflammation following acute myocardial infarction has gained increasing importance as a target mechanism for therapeutic approaches. We sought to investigate the effect of syngeneic cardiac induced cells (CiC) on myocardial... more
Cellular inflammation following acute myocardial infarction has gained increasing importance as a target mechanism for therapeutic approaches. We sought to investigate the effect of syngeneic cardiac induced cells (CiC) on myocardial inflammation using 18F-FDG PET (Positron emission tomography)-based imaging and the resulting effect on cardiac pump function using cardiac magnetic resonance (CMR) imaging in a mouse model of myocardial infarction. Mice underwent permanent left anterior descending coronary artery (LAD) ligation inducing an acute inflammatory response. The therapy group received an intramyocardial injection of 106 CiC into the border zone of the infarction. Five days after myocardial infarction, 18F-FDG PET was performed under anaesthesia with ketamine and xylazine (KX) to image the inflammatory response in the heart. Flow cytometry of the mononuclear cells in the heart was performed to analyze the inflammatory response. The effect of CiC therapy on cardiac function was...
Research Interests:
Research Interests:
Research Interests:
Intrastriatal injection of botulinum neurotoxin A (BoNT-A) results in improved motor behavior of hemiparkinsonian (hemi-PD) rats, an animal model for Parkinson's disease. The caudate-putamen (CPu), as the main input nucleus of the... more
Intrastriatal injection of botulinum neurotoxin A (BoNT-A) results in improved motor behavior of hemiparkinsonian (hemi-PD) rats, an animal model for Parkinson's disease. The caudate-putamen (CPu), as the main input nucleus of the basal ganglia loop, is fundamentally involved in motor function and directly interacts with the dopaminergic system. To determine receptor-mediated explanations for the BoNT-A effect, we analyzed the dopamine D₂/D₃ receptor (D₂/D₃R) in the CPu of 6-hydroxydopamine (6-OHDA)-induced hemi-PD rats by [F]fallypride-PET/CT scans one, three, and six months post-BoNT-A or -sham-BoNT-A injection. Male Wistar rats were assigned to three different groups: controls, sham-injected hemi-PD rats, and BoNT-A-injected hemi-PD rats. Disease-specific motor impairment was verified by apomorphine and amphetamine rotation testing. Animal-specific magnetic resonance imaging was performed for co-registration and anatomical reference. PET quantification was achieved using PMOD...
Research Interests:
Local drug delivery systems (DDS) have become a favourable approach for the treatment of numerous diseases. Biomedical imaging techniques such as ultrahigh field magnetic resonance imaging (UHF-MRI) offer unique insight into DDS... more
Local drug delivery systems (DDS) have become a favourable approach for the treatment of numerous diseases. Biomedical imaging techniques such as ultrahigh field magnetic resonance imaging (UHF-MRI) offer unique insight into DDS biodegradation in vivo. We describe the establishment of a 7 Tesla MRI routine for longitudinal in vivo examinations of a subconjunctival DDS for the treatment of glaucoma in a rabbit model. In initial in vitro examinations the T2-relaxation times of the polymeric DDS components were assessed. Imaging of enzymatically degraded depot samples in vitro did not reveal changes in sample morphology or T2-relaxation time. Ex vivo investigations with an enucleated porcine eye showed good correlation of anatomical MRI and histological data. In longitudinal in vivo studies in rabbits, we repeatedly scanned the depot in the same animal over the course of 5 months with an in-plane resolution of 130 µm at scan times of less than 30 minutes. The degradation was quantified...
Research Interests:
Transgenic animal models of Aβ pathology provide mechanistic insight into some aspects of Alzheimer disease (AD) pathology related to Aβ accumulation. Quantitative neuroimaging is a possible aid to improve translation of mechanistic... more
Transgenic animal models of Aβ pathology provide mechanistic insight into some aspects of Alzheimer disease (AD) pathology related to Aβ accumulation. Quantitative neuroimaging is a possible aid to improve translation of mechanistic findings in transgenic models to human end phenotypes of brain morphology or function. Therefore, we combined MRI-based morphometry, MRS-based NAA-assessment and quantitative histology of neurons and amyloid plaque load in the APPswe/PS1dE9 mouse model to determine the interrelationship between morphological changes, changes in neuron numbers and amyloid plaque load with reductions of NAA levels as marker of neuronal functional viability. The APPswe/PS1dE9 mouse showed an increase of Aβ plaques, loss of neurons and an impairment of NAA/Cr ratio, which however was not accompanied with brain atrophy. As brain atrophy is one main characteristic in human AD, conclusions from murine to human AD pathology should be drawn with caution.
Research Interests:
The purposes of this study were (1) to characterize embryonic eye development during incubation in ovo and (2) to analyze the putative influence of repetitive ultrahigh-field MRI (UHF-MRI) measurements on this development. A population of... more
The purposes of this study were (1) to characterize embryonic eye development during incubation in ovo and (2) to analyze the putative influence of repetitive ultrahigh-field MRI (UHF-MRI) measurements on this development. A population of 38 fertilized chicken eggs was divided into two sub-groups: two eggs (Group A) were examined repeatedly during the developmental period from embryonic day 1 (E1) to embryonic day 20 (E20) to evaluate the influence of daily MRI scanning. A second larger group of 36 eggs was examined pairwise on one day only, from E3 to E20, and the embryos were sacrificed immediately after MR imaging (Group B). Fast T2-weighted MR sequences provided biometric data on the eye with an in-plane resolution of 74 μm. The data show rapid growth of the eye with a steep increase in intraocular dimensions in all axis directions and in eyeball volume during initial development up to E10, followed by a phase of reduced growth rate in later developmental stages. Comparison of t...
Research Interests:
Multiple evidence in animal models and in humans suggest a beneficial role of cold physical plasma in wound treatment. Yet, risk assessment studies are important to further foster therapeutic advancement and acceptance of cold plasma in... more
Multiple evidence in animal models and in humans suggest a beneficial role of cold physical plasma in wound treatment. Yet, risk assessment studies are important to further foster therapeutic advancement and acceptance of cold plasma in clinics. Accordingly, we investigated the longterm side effects of repetitive plasma treatment over 14 consecutive days in a rodent full-thickness ear wound model. Subsequently, animals were housed for 350 days and sacrificed thereafter. In blood, systemic changes of the proinflammatory cytokines interleukin 1β and tumor necrosis factor α were absent. Similarly, tumor marker levels of α-fetoprotein and calcitonin remained unchanged. Using quantitative PCR, the expression levels of several cytokines and tumor markers in liver, lung, and skin were found to be similar in the control and treatment group as well. Likewise, histological and immunohistochemical analysis failed to detect abnormal morphological changes and the presence of tumor markers such a...
Research Interests:
Research Interests:
The finite element method is used in various approaches to solve biomechanical problems. We present a concept helping in the development of appropriate models of the implant-bone compound based on different software packages. The... more
The finite element method is used in various approaches to solve biomechanical problems. We present a concept helping in the development of appropriate models of the implant-bone compound based on different software packages. The reconstruction of bone morphology is based on computed tomography (CT) data of the designated bone. After the bone is three-dimensionally reconstructed in the CAD-environment, virtual implantation
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Patient-derived tumor cell lines are a powerful tool to analyze the sensitivity of individual tumors to specific therapies in mice. An essential prerequisite for such an approach are reliable quantitative techniques to monitor tumor... more
Patient-derived tumor cell lines are a powerful tool to analyze the sensitivity of individual tumors to specific therapies in mice. An essential prerequisite for such an approach are reliable quantitative techniques to monitor tumor progression in vivo. We have employed HROC24 cells, grown heterotopically in NMRI Foxn1nu mice, as a model of microsatellite instable colorectal cancer to investigate the therapeutic efficiencies of 5'-fluorouracil (5'-FU) and the mutant BRAF inhibitor PLX4720, a vemurafenib analogue, by three independent methods: external measurement by caliper, magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) with 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG). Repeated measure ANOVA by a general linear model revealed that time-dependent changes of anatomic tumor volumes measured by MRI differed significantly from those of anatomic volumes assessed by caliper and metabolic volumes determined by PET/CT. Over the investiga...