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NeuroCure is a Cluster of Excellence in the neurosciences at the Charité ‑ Universitätsmedizin Berlin
Aggravation of dementia in neurodegenerative disorders by local immune activation NeuroCure Principal Investigator: Craig Garner NeuroCure Co-PIs: Ulrich Dirnagl, Matthias Endres, Dietmar Schmitz Collaboration partners: Harald Prüß, Frank Heppner In a number of neurodegenerative disorders, auto-antibodies have been detected suggesting that the immune system may contribute to disease progression. To test this hypothesis, we will explore whether the regional activation of the immune system contributes to neuronal loss in Alzheimer’s disease (AD) and whether or not the passive delivery of human autoantibodies against LgI1 or NMDAR exacerbates synaptic and neuronal loss in mouse models of AD, a condition that would contribute to dementia.
Towards precision medicine in autism spectrum disorder (ASD): Neurobiological mechanisms and predictors of cognitive behavioral therapy in adults with high-functioning ASD NeuroCure Principal Investigator: Isabel Dziobek Collaboration partner: Ludger Tebartz van Elst Moving towards precision medicine in ASD, this project aims to identify neural (brain structure, function and connectivity), genetic, and endocrine social cognition markers that can serve as biomarkers for the correlation and prediction of treatment responses in individuals with ASD. This is an ancillary mechanistic study to a multicenter RCT investigating effectiveness of group psychotherapy (FASTER), and an online training for socio-emotional competencies (SCOTT&EVA) against treatment as usual.
Establishing a comprehensive pre-hospital neuroscience platform NeuroCure Principal Investigators: Matthias Endres, Ulrich Dirnagl Collaboration partners: Heinrich Audebert, Georg Bohner, Jochen Fiebach, Andreas Meisel, Joan Montaner, Guillaume Turc Mobile Stroke Units (MSUs) are ambulances that can initiate intravenous thrombolysis prior to hospital arrival and therefore shorten time to treatment. The project is based on Berlin’s MSU (“STEMO” for “Stroke Einsatz Mobil”). With the evaluation of MSU operations and patients’ outcomes, we aim to optimize dispatch and prehospital care. The development of new emergency diagnostics, both in imaging and laboratory medicine, creates the basics for future pre-hospital care, including the targeted search for suitable biomarkers for the detection and differentiation of strokes, early after onset.
Imaging-guided DBS programming – A prospective double-blind non-inferiority trial (BiStip) NeuroCure Principal Investigator: Andrea Kühn Collaboration partners: Andreas Horn, Gerd-Helge Schneider, Katharina Faust Deep brain stimulation is a surgical therapy method for advanced idiopathic Parkinson's syndrome. Essential for the success of treatment is the often very complex postoperative adjustment of the stimulation parameters. In this study, a new procedure is to be tested in which the optimal stimulation parameters are determined based on the individual position of the stimulation electrodes determined by imaging techniques. The aim is to show in a 2x2 crossover design that the procedure is not inferior in terms of motor improvement compared to clinical routine.
Comprehensive approaches to study pathophysiological mechanisms of neuropsychiatric disorders – use of human tissue NeuroCure Principal Investigator: Dietmar Schmitz NeuroCure Co-PIs: Matthias Endres, Matthew Larkum, Christian Rosenmund Collaboration partners: Pawel Fidzinski, Jörg Geiger, Martin Holtkamp, Imre Vida, Peter Vajkoczy, Ulf Schneider The objective of our project is to establish a large scale platform for the functional investigation of pathomechanisms in neurological-psychiatric disorders using acute human brain slices and human organotypic brain slice cultures. We will focus our analysis on the hippocampal formation and temporal cortices. By direct investigation of human brain tissue and thus overcoming limitations of animal models, the aim of the platform is to reduce the translational gap between basic research and clinical application in neurology. In addition, replacement of animal brain tissue with human brain tissue will lead to minimization of animal suffering in neuroscience research in accordance with the “3R” principles of animal use in scientific procedures.
Developmental and functional disorders of the brain stem and lower cranial nerves in children with congenital orofacial dyspraxia or congenital vocal cord paralysis NeuroCure Principal Investigator: Markus Schülke NeuroCure Co-PI: Carmen Birchmeier Collaboration partners: Saskia Rohrbach-Volland, Prof. Gary Lewin Dysfunction of the Medulla oblongata or the sensory and motor components of the lower cranial nerves can be caused by the deficiency of specific transcriptional networks crucial for their development, or by alterations in crucial genes controlled by these networks. Such disturbances do cause severe vocalization and breathing deficits in the mouse model. With the proposed project, we want to screen children with congenital orofacial dyspraxia, with congenital vocal cord paralysis, or with early parasympathetic dysfunction for mutations in these transcription factors in order to learn more about cranial nerve development and their specification into motor and sensory neurons.
The Brain4Lab Data Management and Analysis Platform for Improved Diagnosis, Therapy and Prognostication in Neurocritical Care Medicine (Brain4Lab DM&AP) NeuroCure Principal Investigators: Ulrich Dirnagl, Matthias Endres Collaboration partners: Andreas Meisel, Franziska Scheibe, Petra Ritter, Jens Dreier, Harald Prüß, Christoph Leithner, Stefan Wolf, Michael Scheel, Christian Meisel Daniel Strech, Andreas Heinz Brain4Lab DM&AP offers a highly specialized research infrastructure within the framework of the Brain4Lab. This infrastructure sits at the interface between the interdisciplinary NeuroIntensive Care Unit 102i (NICU), Charité stroke units (SU), NeuroCure and BIH, thus improving prognostication, diagnosis and therapy in Neurocritical Care Medicine. It does this by combining different techniques like neuroimaging and multimodal real-time neuromonitoring with data storing and analysis in a data warehouse system and through Virtual Brain simulations.
Does early-life stress promote protracted neuroinflammation in humans? Towards understanding early developmental origins of accelerated brain ageing NeuroCure Principal Investigator: Christine Heim Collaboration partners: Claudia Buss, Sonja Entringer This project addresses the developmental origins of neuroinflammation and its relationship to brain ageing and age-related brain disorders in humans. Using multimodal neuroimaging, we will test whether early-life stress (ELS) is associated with neuroinflammation and accelerated brain ageing. We will link these markers to cognitive decline and ageing-related disease and test whether peripheral markers of inflammation and immunosenescence reflect neuroinflammation and brain ageing after ELS.
A systematic multilevel comparison between physiological signatures of exogenous and endogenous psychoses NeuroCure Principal Investigator: Andreas Heinz NeuroCure Co-PI: Matthias Endres Collaboration partners: Felix Bermpohl, Benjamin Blankertz, Eva Brandl, Stephan Brandt, Susanne Koch, Stephan Köhler, Tim Neumann, Josef Priller, Harald Prüss, Michael Rapp, Daniel Senkowski, Surjo R. Soekadar, Claudia Spies, Sascha Treskatsch Following a dimensional approach, we will systematically assess the psychopathological, immunological and neurophysiological correlates of psychotic disorders, including delirium and the schizophrenia spectrum. We will compare frequency of visual versus acoustic hallucinations, self-disorders and clouding of consciousness. Additionally, we will assess electroencephalography and biomarkers indicating autoimmune processes among patients with schizophrenia and schizoaffective disorders, psychotic depression and mania, delirium and acute organic hallucinations and delusions.
BrainBank NeuroCure Principal Investigator: Frank Heppner Collaboration partners: all NeuroCure PIs,Péter Körtvélyessy The BrainBank Nucleus collects and stores central nervous system tissues in a systematic and standardized fashion, with an emphasis on neurodegenerative diseases such as Alzheimer’s Disease (AD). To enable the assembly of clinically well-characterized cases, the BrainBank actively engages with its clinical partners from neurology and psychiatry to identify and phenotype patients at the beginning of the disease or during the lifetime, and to correlate clinical courses to pathological changes and tissue signatures at the time of death. Based on recent preclinical, genetic and bioinformatic data demonstrating that immune system actions contribute to AD pathogenesis, we specifically aim to relate the phenotypic spectrum of sporadic AD subjects to their specific immune risk factor profile within the same vs. different AD families.
