PROJECT: JTC2017: MISST

Stroke is one of the major causes of death and severe long-term disability worldwide. Stroke leads to local destruction of brain tissue, however, more recently it was recognized that it also causes atrophy of healthy brain regions remote to the injury site. The mechanisms and the significance of this remote action of stroke are unknown yet. Based on preliminary experiments we hypothesize that this phenomenon is caused by spatio-temporal reorganizations of the brain on the level of neuronal dendrites and synapses. Therefore the aim of the current MISST consortium is to investigate the basis of these so far missed consequences of stroke by using a novel clinically relevant mouse stroke model, in vivo super-high resolution STED microscopy, 2-photon microscopy in awake mice, multi-dimensional behavioral phenotyping, and cutting-edge 3D whole neuron and whole brain imaging using tissue clearing and microanatomical reconstruction. These state-of-the-art technologies will be used to examine the structural and cellular changes occurring in the hemisphere contralateral to the infarcted brain over time. Finally, we will analyze how opto- and pharmacogenetic neuronal stimulation, pharmacological inhibition of synaptic degradation, and rehabilitative interventions such as physical activity and enriched environment affect synaptic reorganization thereby outlining new therapeutic strategies for long-term disabilities after stroke.