Myeloid Cell Diversity and Ischemic Stroke

The 'translational blockade' in stroke medicine may be related in part to the fact that the interplay of the various pathomechanisms is far more complex than previously thought. In particular, many inflammatory mechanisms involved in cell damage in the early phase of brain ischemia may be conducive to recovery and regeneration in later stages. After stroke, there are dynamic changes in cell-cell interactions involving microglia, the immune cells resident in the central nervous system (CNS).
Microglia are activated after injury, resulting in increased phagocytic capacity, acquisition of amoeboid morphology, and/or increased proliferation rate. In addition, monocyte-derived blood-born macrophages (Mo/MΦ) populate the infarct but are difficult to distinguish from resident microglia based on morphological criteria alone.
Importantly, modulation of these different myeloid cell types clearly influences acute and long-term outcomes after stroke. However, the precise mechanisms that shape the cerebral microenvironment after brain ischemia and influence myeloid cell interactions, proliferation, and function are not well defined. Moreover, information on human stroke, especially on the properties of myeloid cells, is sparse.

Therefore, in this project, we aim to elucidate the role of myeloid cell subsets, particularly microglia and Mo/MΦ, in the pathogenesis of ischemic stroke.
Using different transgenic mouse models, we will further characterize myeloid cell turnover after stroke. Specific pharmacological treatment approaches will be applied to investigate the effects on microglial proliferation, function, and stroke outcome using a complex endpoint analysis that includes histological, electrophysiological, and behavioral assays. Finally, in a complementary translational approach, autopsy samples from human stroke victims will be analyzed.
Overall, we will elucidate the local factors that modulate cell properties and interactions between myeloid and other CNS cells after stroke.