The Lab Starts a New Swiss National Science Foundation Project on February 1: Nanoscale Structure of the Microvascular-astrocytic Interface

Electron microscopy (EM)-based reconstructions of the peri-microvascular space have claimed near complete coverage by astrocytic endfeet. Recent data however suggest that this level of coverage is significantly overestimated due to a near-complete depletion of the ECS caused by the chemical fixation protocol widely used for EM tissue preparation. Such a lose astrocytic coverage points toward a parallel route of glucose through ECS. The present project aims at systematically quantifying the astrocytic endfeet coverage of the brain capillaries using state-of-the-art cryofixation and serial EM. Obtained quantifications will be compared to ground truth obtained by in vivo Stimulated Emission Depletion (STED) microscopy. The project will also characterize structural interfaces between endothelial cells, pericytes and astrocytes and will investigate the spatio-temporal dynamics of endothelial cell remodeling after induction of capillary occlusions mimicking microstroke. The entire project is a technical tour de force which profits from an international collaborative network of world leaders in the field of EM, correlative and in vivo imaging.