PIs: L. Dimou, K. Danzer

Despite intensive research over the past decades, the impact of trauma and its consequences on brain function and initiation of neurodegenerative diseases is not sufficiently unraveled. The understanding of the underlying cellular mechanisms is of great importance not only for prevention of neurodegeneration but also for therapeutic targeting after traumatic injury. We could show that after a traumatic brain injury (TBI) glial cells react in an orchestrated temporal and regional manner, characterized by a long-lasting rapid reaction of microglia and a subsequent astrocyte reaction, while NG2-glia respond in a fast but transient manner. Notably, the blockage of the increase in number of NG2-glia after brain injury leads to a delay in wound closure probably associated with changes in the reaction of resident and infiltration of peripheral immune cells. As trauma has been implicated in the development of Parkinson ́s Disease (PD), we aim here to unravel the underlying mechanisms linking trauma and inflammation to neurodegeneration. We focus on both, central as well as peripheral trauma, and address glial cells ́ reaction, neuroinflammation, adult neurogenesis, protein aggregation, propagation of disease pathology and PD as a comorbidity. Our two coordinated paradigms are: a) Trauma, independent of the site of injury, can change the pathology, disease onset and severity of PD and b) PD, as a comorbidity, affects the outcome after traumatic processes. For this, we are taking advantage of a novel mouse model of PD generated in our lab and innovative techniques to get insights in the cross reaction between trauma and PD.