Team : NAGERL
Multi-scale investigation of synaptic dysfunction after stroke
Project Leader(s): Luc Mercier and Stephane Bancelin
Stroke is the leading cause of long-term disability in Europe and an increasing health problem in aging societies worldwide. While effective treatments were developed for acute stroke in recent years, patients surviving a stroke often suffer from chronic sequels like depression, progressive cognitive dysfunction or even dementia of unknown origin resulting in significant morbidity. The mechanisms responsible for these chronic disorders are unknown and therapeutic options therefore not available. Data from animals and humans demonstrate that chronic neurological dysfunction after stroke does not only affect the initially ischemic tissue, but also distant brain regions connected to the area damaged by stroke. Recent experimental results from one of the partners’ laboratory suggest that these changes are associated with structural and molecular changes at the level of synapses. Based on these findings the hypothesis of the current application is that acute stroke triggers chronic changes in remote brain regions (diaschisis) which may further impair neurological function or even inhibit regenerative processes following stroke. The scientific aim of the current project is therefore to characterize and understand the structural and molecular basis of chronic remote changes occurring after stroke on the synaptic level and to use this knowledge to develop novel therapeutic strategies which may protect the brain from chronic synaptic dysfunction and functional decline. In order to achieve this overall goal, we brought together six internationally competitive European research teams with unique experience and technical excellence in the investigation of synaptic function and stroke. This consortium of excellence will use state-of-the-art technology (in vivo n STED microscopy, tissue clearing and 3D imaging by light-sheet microscopy, 3D reconstruction of mouse and human neurons, and high-resolution 7T small animal MRI) to investigate the synaptic changes occurring after stroke in novel animal models of chronic stroke and in tissue from stroke patients using a multi-level approach. Thereby a unique translational research platform will be created which has the means and the potential to generate and validate novel therapeutic concepts for patients suffering from chronic stroke.