Transition from acute to chronic neuroinflammation
Neuroinflammation is the reaction of the immune system of the brain that occurs during various diseases of the central nervous system. Acute activation of microglia and astrocytes may harbour beneficial effects. Under circumstances not yet well understood, an acute/focal neuroinflammatory reaction turns into a chronic and spread type of immune activation. This transition from acute/focal to chronic and spread immune reaction is likely to have detrimental consequences for the brain and likely to contribute to the progression of exactly the disease, which initially had stimulated the immune reaction. Alternatively, chronic and spread inflammation may be self-originated. The present proposal will discriminate between these possibilities and study the mechanisms of transition between various stages of immune activation in preclinical models across various diseases that possess an inflammatory component. Moreover, we aim to identify gene network hubs that mark key steps of this transition in order to find points of intervention. Interference with such key steps will be tested. Moreover, we will validate our findings using human cerebrospinal fluid and brain tissue from intermediate phases of the respective disease. We strongly suggest that the results of this study will have wider implications for additional CNS disorders, which harbour an inflammatory component.
Gene targeting in the brain, Molecular modelling techniques, omics approaches, acute neuroinflammation, chronic neuroinflammation
2014 - 2018