Intravital microscopy of EAE lesions
Neuronal damage is the correlate for long-term disability in patients suffering from Multiple Sclerosis. Here we would like to investigate the involvement of microglia and macrophages in the processes leading to damage at the axon-oligodendroglial unit by use of intravital imaging of damage mechanisms and by human in vitro culture models. We aim to monitor the complex processes of the immune cell attack onto myelinated axons and delineate the chain of cause and effect. We will employ transgenic mice which express distinct fluorescent molecules in microglia and macrophages and report Ca2+ dynamics in the neuronal compartment, which gives a functional read-out of these processes. In vivo imaging will rely on semi-quantitative measurement of neuronal Ca2+ fluxes in EAE lesions of anaesthetized mice, which carry a Ca2+ sensor protein. The vision of this project is to open up new perspectives to specifically target immune-mediated neuronal damage processes in inflammatory CNS disease.