Fluid Dynamics of the Central Nervous System
3D Functional Anatomy and Pathophysiology in Mouse Models
In this Sinergia project funded by the Swiss National Science Foundation, we aim to consolidate the understanding of central nervous system (CNS) fluid physiology and how it changes with age, neuroinflammation and neurodegeneration – with direct relevance for the understanding of brain pathologies, including multiple sclerosis and Alzheimer’s disease. This research endeavor is a collaboration between the Interface Group, the Theodor Kocher Institute of the University of Bern and the Biomaterials Science Center of the University of Basel, in partnership with the French National Synchrotron Facility SOLEIL and the European Synchrotron Radiation Facility (ESRF).
Current understanding of CNS fluid homeostasis
Advances in intravital imaging technologies have enabled an unprecedented view into the fluid spaces of the central nervous system (CNS), challenging our current understanding of CNS fluid physiology and our brain’s immune privilege. But this has also led to a segregation of CNS research into microscopic investigations of biology in mice and macroscopic studies of biophysics in humans, without clear agreement on the production mechanisms, exit locations, driving forces and routes of CNS fluids.
The CNS fluid spaces and barriers are also of fundamental importance for CNS immune surveillance and the progression of neuroinflammatory diseases. In multiple sclerosis, lesions are first compartmentalized in periventricular areas or the perivascular spaces and only reach the CNS parenchyma proper once CNS barriers are breached. Understanding how neuroinflammation, neurodegeneration and changes in CSF dynamics are interlinked is a key requirement for the development of novel therapeutic strategies.
Our approach
We aim to establish a comprehensive understanding of CSF dynamics, associated transport processes, and corresponding CNS barriers in mouse models, and then analyze changes due to aging, neuroinflammation, and neurodegeneration. Our team consists of biologists, veterinarians, physicists, physiologists, neuroscientists, and engineers that bring together the required cross-disciplinary expertise. We will pursue our goals by a unique combination of technologies including new reporter mice, in vivo synchrotron radiation-based micro computed tomography (SRµCT), magnetic resonance imaging (MRI), near-infrared and two-photon fluorescence imaging of CSF pathways and CNS barriers, and computational modelling.