Members
Head of Institute
Hannover Medical School
Institute for Laboratory Animal Science and Central Animal Facility
Hannover
Dr. Christine Häger
Group Leader
Hannover Medical School
Institute for Laboratory Animal Science and Central Animal Facility
Hannover
Research sketch
The Institute for Laboratory Animal Science and the Central Animal Facility of the Hannover Medical School, one of the largest experimental animal facilities in Europe, are closely intertwined and directed in personal union; therefore, the group aims at interrelating basic research to laboratory animal science. One of our main research interests is the evidence-based severity assessment in laboratory animals. In well-established animal models, particularly for inflammatory bowel disease (IBD) and stress, we focus on the investigation of the pathophysiology of the gastro-intestinal mucosa, gnotobiology and infection models, as well as projects related to laboratory animal medicine. By behavioural phenotyping and physiological and biochemical analyses we aim at identifying objective, quantifiable and standardized severity assessment parameters in models of IBD, stress and surgery to provide animal welfare based recommendations for severity assessment in laboratory animals.
Selected Publications:
Häger, C., L. M. Keubler, S. Biernot, J. Dietrich, S. Buchheister, M. Buettner and A. Bleich (2015). "Time to Integrate to Nest Test Evaluation in a Mouse DSS-Colitis Model." PLoS One 10(12): e0143824.
Häger, C., S. Biernot, M. Buettner, S. Glage, L. M. Keubler, N. Held, E. M. Bleich, K. Otto, C. W. Muller, S. Decker, S. R. Talbot and A. Bleich (2017). "The Sheep Grimace Scale as an indicator of post-operative distress and pain in laboratory sheep." PLoS One 12(4): e0175839.
Basic, M., L. M. Keubler, M. Buettner, M. Achard, G. Breves, B. Schroder, A. Smoczek, A. Jorns, D. Wedekind, N. H. Zschemisch, C. Gunther, D. Neumann, S. Lienenklaus, S. Weiss, M. W. Hornef, M. Mahler and A. Bleich (2014). "Norovirus triggered microbiota-driven mucosal inflammation in interleukin 10-deficient mice." Inflamm Bowel Dis 20(3): 431-443.
Professor and Director
Institute for Laboratory Animal Science and Central Animal Facility
RWTH Aachen University, Medical Faculty
Aachen
Research sketch
The Institute for Laboratory Animal Science (ILAS) is part of the RWTH Aachen University and the Medical Faculty and offers the research platform and central animal facility for scientists studying animal models in Aachen. There is also a close partnership with the Helmholtz Foundation. Besides breeding and maintenance of transgenic and knockout mice and rats under strict specific-pathogen-free (SPF) conditions, the ILAS also has the capacity for several large animals as porcine, sheep and calves.
One of the central research areas of the ILAS deals with surgical methods and procedures, especially in the field of liver resection and liver and kidney transplantation. Consequently, the contribution of the ILAS will be severity assessment in a liver resection and a liver transplantation model in rats as well as a kidney transplantation model in pigs.
In the research field of liver fibrosis, there is also the focus on severity assessment and refinement of different mouse models, particularly on chemically induced models as the CCL4 model.
Selected Publications:
Drude N, Pawlowsky K, Tanaka H, Fukushima K, Kögel B, Tolba RH. Severity assessment in rabbits after partial hepatectomy: Part II. Lab Anim. 2016 Dec;50(6): 468-475.
Kanzler S, Rix A, Czigany Z, Tanaka H, Fukushima K, Kögel B, Pawlowsky K, Tolba RH. Recommendation for severity assessment following liver resection and liver transplantation in rats: Part I. Lab Anim. 2016 Dec;50(6): 459-467.
Tolba RH, Czigány Z, Osorio Lujan S, Oltean M, Axelsson M, Akelina Y, Di Cataldo A, Miko I, Furka I, Dahmen U, Kobayashi E, Ionac M, Nemeth N. Defining Standards in Experimental Microsurgical Training: Recommendations of the European Society for Surgical Research (ESSR) and the International Society for Experimental Microsurgery (ISEM). Eur Surg Res. 2017 Jul 26;58(5-6):246-262. doi: 10.1159/000479005. [Epub ahead of print] PMID: 28746936.
Group Leader
University of Zurich
University Hospital Zurich
Division of Surgical Research
Zurich
Prof. Dr. med. vet. Margarete Arras, Dipl. ECLAM
University of Zurich
University Hospital Zurich
Division of Surgical Research
Zurich
Research Sketch
Our research focuses on the improvement of pain assessment and pain treatment in laboratory rodents. Pain treatment is an important animal welfare concern, but has additionally significant scientific and methodological implications for the design of experiments and the quality of the resulting data.
To ensure high-quality scientific outcomes and humane treatment of laboratory animals, sufficient anesthesia, reliable alleviation of pain and recovery supporting housing conditions are essential. In the past, we have developed and evaluated physiology and behavior based pain assessment tools for laboratory rodents. These methods have been used to improve anesthesia and analgesia protocols for surgery in mice and rats.
Selected Publications
Jirkof, P., Tourvieille, A., Cinelli, P., & Arras, M. (2015). "Buprenorphine for pain relief in mice: repeated injections vs sustained-release depot formulation". Laboratory animals, 49(3), 177-187.
Jirkof, P., Cesarovic, N., Rettich, A., Nicholls, F., Seifert, B., & Arras, M. (2010). "Burrowing behavior as an indicator of post-laparotomy pain in mice". Frontiers in behavioral neuroscience, 4.
Arras, M., Rettich, A., Cinelli, P., Kasermann, H. P., & Burki, K. (2007). "Assessment of post-laparotomy pain in laboratory mice by telemetric recording of heart rate and heart rate variability". BMC veterinary research, 3(1), 16.
Senior physician
Department of Anaesthesiology,
RWTH Aachen University, Medical Faculty
Aachen
Research Sketch
The aim of this project is to develop further camera-based techniques and vital data-derived parameters to estimate severity in various animal models. First, long wave infrared (IRT), near (short wave) infrared (NIR) and radar-based algorithms will be used to assess vital signs from diverse large and small animals. Second, local and systemic inflammation phenomena will be examined by using camera-based methods. In an own porcine animal trial, we will examine if it is possible to monitor the beginning and the course of inflammation (induced by lipopolysaccharide) by contactless techniques in different degrees of severity. Third, assessed vitals and additional parameters will be used to develop aggregated scores classifying severity, distress and pain. Finally, transferability of algorithms developed from sedated animals to free-roaming ones as well as from large animals to small ones will be examined.
Selected Publications
Pereira CB, Czaplik M, Blanik N, Rossaint R, Blazek V, Leonhardt S. "Contact-free monitoring of circulation and perfusion dynamics based on the analysis of thermal imagery". Biomed Opt Express. 2014; 5: 1075-1089.
Pereira CB, Yu X, Czaplik M, Rossaint R, Blazek V, Leonhardt S. "Remote monitoring of breathing dynamics using infrared thermography". Biomed Opt Express. 2015; 16;6(11):4378-4394.
Wang S, Pohl A, Jaeschke T, Czaplik M, Kony M, Leonhardt S, Pohl N. "A novel ultra-wideband 80 GHz FMCW radar system for contactless monitoring of vital signs". Conf Proc IEEE Eng Med Biol Soc. 2015; 2015: 4978-4981.
Head of Research Group
Central Institute of Mental Health, Mannheim
Mannheim Faculty/ University of Heidelberg
Mannheim/ Heidelberg
Research Sketch
A core competence of our laboratory is to establish reliable and valid models for neuropsychiatric disorders, which can be analyzed by multiple behavioral, neurochemical and functional assays. We use targeted mutagenesis, pharmacological challenge and acute or chronic stress procedures to induce defined syndromes in mice, which lead to alterations of the animals’ emotional or cognitive behaviors. This serves to model essential features of complex psychiatric diseases, such as anxiety, depression and schizophrenia. We have established a panel of behavioral tests by which we analyse postulated core symptoms and associated symptoms.
The role of maintenance conditions and severity assessment has already been an important research aspect for us, mostly with respect to standardise adversity and eliminate confounding factors. We aim to determine the severity of psychiatric animal models and compare it with somatic disease models, in order to contribute to an evidence-based evaluation of distresses in laboratory animals. Ultimately, our evaluations should result in the usage of the least severe but highly valid models and handling and maintenance conditions in the future.
Selected Publications
Mallien AS, Palme R, Richetto J, Muzzillo C, Richter SH, Vogt MA, Riva MA, Vollmayr B, Gass P. "Daily exposure to a touchscreen-paradigm and associated food restriction evokes an increase in adrenocortical and neural activity in mice". Horm Behav 2016;301:96-101.
Richter SH, Sartorius A, Gass P, Vollmayr B. "A matter of timing: harm reduction in learned helplessness". Behav Brain Funct 2014;10:41,eCollection.
Chourbaji S, Hörtnagl H, Molteni R, Riva M, Gass P, Hellweg R. "The impact of environmental enrichment on sex-specific neurochemical circuitries - effects on brain-derived neurotrophic factor and the serotonergic system". Neuroscience 2012;220:267-76.
Chair of Experimental Molecular Imaging
RWTH Aachen University, Medical Faculty
Aachen
Research Sketch
The Institute of Experimental Molecular Imaging at the Medical Faculty of RWTH Aachen aims at the development of novel diagnostic, theranostic and therapeutic probes, advanced imaging technologies, and image analysis tools.
Selected Publications
Tsvetkova Y., Beztsinna N., Baues M., Klein D., Rix A., Golombek S., Al Rawashdeh W., Gremse F., Barz M., Koynov K., Banala S., Lederle W., Lammers T., Kiessling F. (2017) "Balancing Passive and Active Targeting to Different Tumor Compartments Using Riboflavin-functionalized Polymeric Nanocarriers". Nano Lett, e-pub ahead of print.
Lammers T., Koczera P., Fokong S., Gremse F., Ehling J., Vogt M., Pich A., Storm G., van Zandvoort M., Kiessling F. (2015) "Theranostic USPIO-loaded microbubbles for mediating and monitoring blood-brain barrier permeation". Adv Funct Mater, 25:36-43.
Kunjachan S., Pola R., Gremse F., Theek B., Ehling J., Moeckel D., Hermanns-Sachweh B., Pechar M., Ulbrich K., Hennink W.E., Storm G., Lederle W., Kiessling F.*, Lammers T*. (2014) "Passive vs. active tumor targeting using RGD- and NGR-modified polymeric nanomedicines". Nano Lett, 14:972-81.
Head of Unit
German Federal Institute for Risk Assessment (BfR)
Unit Animal Protection and Laboratory Animal Science Berlin
Osnabrück
Research Sketch
Mice will be given the choice between a wide variety of goods in order to derive a scale on which likes and dislikes of unknown valence can be rated for future severity assessment. In addition a newly developed cognitive bias test paradigm will allow assessing the impact of treatments on the future expectation of the tested animals with regard to 'optimistic' or 'pessimistic' valences.
Selected Publications
Brust, V., P. M. Schindler, and L. Lewejohann. 2015. "Lifetime development of behavioural phenotype in the house mouse (Mus musculus)". Front. Zool. 12 Suppl 1: S17.
Kloke, V., R. S. Schreiber, C. Bodden, J. Möllers, H. Ruhmann, S. Kaiser, K.-P. Lesch, N. Sachser, and L. Lewejohann. 2014. "Hope for the best or prepare for the worst? Towards a spatial cognitive bias test for mice". PLoS One 9: e105431.
Karabeg, M. M., S. Grauthoff, S. Y. Kollert, M. Weidner, R. S. Heiming, F. Jansen, S. Popp, S. Kaiser, K.-P. Lesch, N. Sachser, A. G. Schmitt, and L. Lewejohann. 2013. "5-HTT deficiency affects neuroplasticity and increases stress sensitivity resulting in altered spatial learning performance in the Morris water maze but not in the Barnes maze". PLoS One 8: e78238.
Translational Neurosurgery and Neurobiology
Department of Neurosurgery
RWTH Aachen University, Medical Faculty
Aachen
Research Sketch
In our research group we investigate how the blood flow is regulated in the brain according to the regional metabolic demand. We are interested in the spatial and temporal characteristics of the blood flow responses to functional activation forming the basis for non-invasive functional brain imaging, and in the mechanisms and mediators of neurovascular coupling, using rat and mouse models of functional activation. This knowledge of the physiological regulation is important to understand what goes wrong under pathophysiological conditions. Our pathophysiological research specifically aims at better understanding the functional impairment of the vasculature after subarachnoid hemorrhage (SAH) and cerebral ischemia and its contribution to brain lesion development. In-vivo rodent models of SAH and stroke are accomplished by the in-vitro model of the isolated cerebral artery. To measure blood flow and hemoglobin oxygenation we apply optical methods as laser Doppler flowmetry, laser speckle contrast analysis and optical spectroscopy.
Selected Publications
Pinkernell S, Becker K, Lindauer U. "Severity assessment and scoring for neurosurgical models in rodents". Lab Anim. 2016 Dec;50(6):442-452.
Ghosh M, Balbi M, Hellal F, Dichgans M, Lindauer U, Plesnila N. "Pericytes are involved in the pathogenesis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy". Ann Neurol. 2015 Dec;78(6):887-900.
Fernández-Klett F, Offenhauser N, Dirnagl U, Priller J, Lindauer U. "Pericytes in capillaries are contractile in vivo, but arterioles mediate functional hyperemia in the mouse brain". Proc Natl Acad Sci U S A. 2010 Dec 21;107(51):22290-5.
Institute of Pharmacology, Toxicology, and Pharmacy
Faculty of Veterinary Medicine,
Ludwig-Maximilians-University
Munich
Research sketch
The main focus of our research is the pathophysiology and pharmacology of epilepsy, epileptic encephalopathies, and other neurological diseases. Novel biomarker and target candidates for therapeutic management or for preventive approaches are identified and validated in chronic rodent models. Our facilities comprise comprehensive specialized equipment for chronic video/EEG monitoring and behavioral analysis as a basis for preclinical efficacy and tolerability testing. Considering the complex cellular and network alterations characterizing the epileptic brain, in-vivo models can so far only be partially replaced by in-vitro or ex-vivo investigations. Therefore, our team strives to increase our understanding of the animal’s experience in chronic models with recurrent seizures. Based on behavioral, physiological and biochemical analyses combined with molecular imaging approaches, we aim to develop tailored evidence-based severity assessment schemes. These will render a basis for subsequent validation of refinement measures and implementation of minimal severity conditions. Moreover, we will provide animal-welfare based recommendations for model selection based on the gain-in-knowledge.
Publications
Bogdanovic RM, Syvänen S, Michler C, Russmann R, Eriksson J, Windhorst A, Lammertsma A, de Lange E, Voskuyl R, Potschka H. 2014 "(R)-[11C]PK11195 brain uptake as a biomarker of inflammation and antiepileptic drug resistance: Evaluation in a rat epilepsy model". Neuropharmacology. 85:104-112.
Von Rüden EL, Bogdanovic RM, Wotjak CT, Potschka H. 2015 "Inhibition of monoacylglycerol lipase mediates a cannabinoid 1-receptor dependent delay of kindling progression in mice". Neurobiol Dis. 77:238-245.
Walker A, Russmann V, Deeg CA, von Toerne C, Kleinwort KJ, Szober C, Rettenbeck ML, von Rüden EL, Goc J, Ongerth T, Boes K, Salvamoser JD, Vezzani A, Hauck SM, Potschka H. 2016 "Proteomic profiling of epileptogenesis in a rat model: focus on inflammation". Brain Behav Immun. 53:138-158.
Head of Laboratories for Experimental Neurosurgery
Hannover Medical School
Department of Neurosurgery
Hannover
Research Sketch
Our aim is to develop severity assessment schemes suitable for the analysis of well-being in rat models for movement disorders and neuropsychiatric conditions that involve complex neurosurgical intervention, neuromodulation by systemic or intracranial injections, continuous neuronal stimulation or recording with tethered electrodes, and testing of motor and associative-limbic behaviour. We will also validate these approaches as humane endpoint criteria after intracranial tumor formation. Clinical scoring and body weight measures will be combined with spontaneous species specific behaviour, motor activity and limbic behavior, which will be complemented by telemetric measures of body temperature and heart rate, as well as determination of biomarkers of stress.
We envision that a correlation analysis between all measures will identify patterns that can be used to refine postoperative pain management and determination of humane endpoint, which can also be used for evidence-based grading of the severity of repeated experimental manipulation that involve certain amount of restraint.
Publications
Alam M, Rumpel R, Jin X, von Wrangel C, Tschirner SK, Krauss JK, Grothe C, Ratzka A, Schwabe K. "Altered somatosensory cortex neuronal activity in a rat model of Parkinson's disease and levodopa-induced dyskinesias". Exp Neurol. 2017 Aug;294:19-31.
Angelov SD, Dietrich C, Krauss JK, Schwabe K. "Effect of deep brain stimulation in rats selectively bred for reduced prepulse inhibition". Brain Stimul. 2014 Jul-Aug;7(4):595-602.
Borrmann N, Friedrich S, Schwabe K, Hedrich HJ, Krauss JK, Knapp WH, Nakamura M, Meyer GJ, Walte A. "Systemic treatment with 4-211Atphenylalanine enhances survival of rats with intracranial glioblastoma". Nuklearmedizin. 2013 Dec 13;52(6):212-21.
Hannover Medical School
Institute of Molecular and Translational Therapeutic Strategies (IMTTS)
Hannover
Research Sketch
Using multiple in vitro screenings, we will access dose-dependent cytotoxicity effects and inflammatory reactions for several IncRNA meg3 inhibitors. For 3 doses the 10 most safest IncRNA meg3 inhibitors will be tested in mice to assess potential kidney and liver toxicology. Based on this results 3 candidates will be used for an intensive assessment of animal stress. Cardiac monitoring of mice after cardiac stress (Angiotensin-II-treatment and myocardial infarction) as well as with and without anti-meg3 treatment will be performed via MRI imaging for cardiac function and fibrotic areas, together with P01 (Bleich/Häger). Additionally, we will perform automatic wheel-running, telemetry methods and TINT (time-to-integrate-to-nest-test).
In selected organs of mice where phenotypically abnormalities were identified, we will perform transcriptome analyses to search for deregulated marker genes that correlate well with phenotypically observed organ abnormalities. To create a panel of stress-sensitive miRNAs, we will receive plasma from several disease models from our collaborating partners. This set of conserved miRNAs will be cross-validated in prospective animal studies and compared to other stress-sensitive markers such as cortisol, oxytocin (P01, Bleich/Häger) or inflammatory markers (P02, Tolba).
Selected Publications
Piccoli MT, Gupta S, Viereck J, Foinquinos A, Samolovac S, Kramer F, Garg A, Remke J, Zimmer K, Batkai S, Thum T. "Inhibition of the Cardiac Fibroblast-Enriched lncRNA Meg3 Prevents Cardiac Fibrosis and Diastolic Dysfunction". Circ Res. 2017 Jun 19. pii: CIRCRESAHA.117.310624.
Bär C, Chatterjee S, Thum T. "Long Noncoding RNAs in Cardiovascular Pathology, Diagnosis, and Therapy". Circulation. 2016 Nov 8;134(19):1484-1499.
Professor, Director of the German Primate Center
Head of the Cognitive Neuroscience Laboratory
Göttingen
Prof. Dr. Alexander Gail
Head of Sensorimotor Group
German Primate Center - Leibniz Institute for Primate Research
Göttingen
Rostock University Medical Center
Institute for Experimental Surgery
Rostock
Prof. Dr. med. Brigitte Vollmar
Head of Institute
Rostock University Medical Center
Institute for Experimental Surgery
Rostock
Research Sketch
An important prerequisite for conducting animal experiments in Europe is a harm-benefit analysis, which evaluates, if the harm to the animals is justified by the expected outcome. Judging the animal distress is an essential part of this concept. We are especially interested in analyzing the course of distress in animals during the progression of chronic diseases. Developing therapies for chronic diseases by using animal models is becoming increasingly important, since the expectation of life and consequently the prevalence of chronic diseases increase in many European countries. However, animal models for chronic diseases are often automatically considered to cause longer lasting and therefore more severe distress. This reduces the chance to get the permission to perform studies to alleviate chronic diseases or to understand basic scientific aspects of these pathologies. In order to be able to choose appropriate animal models with minimal distress in the future we pursue to establish an objective grading system of distress. In addition, it is our goal to evaluate the validity of distinct methods of measuring animal distress and to compare their sensitivity as well as their practicability.
Selected Publications
Abshagen K, Rotberg T, Genz B, Vollmar B. "No significant impact of Foxf1 siRNA treatment in acute and chronic CCl4 liver injury. Exp Biol Med (Maywood)". 2017;1:1535370217716425. [Epub ahead of print]
Kuhla A, Rühlmann C, Lindner T, Polei S, Hadlich S, Krause BJ, Vollmar B, Teipel SJ. "APPswe/PS1dE9 mice with cortical amyloid pathology show a reduced NAA/Cr ratio without apparent brain atrophy: A MRS and MRI study". Neuroimage Clin. 2017;15:581-586.
Zechner D, Bürtin F, Albert AC, Zhang X, Kumstel S, Schönrogge M, Graffunder J, Shih HY, Müller S, Radecke T, Jaster R, Vollmar B. "Intratumoral heterogeneity of the therapeutical response to gemcitabine and metformin". Oncotarget. 2016;7(35):56395-56407.