Microglia-PET as a surrogate marker for post-stroke neuroinflammation

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This project aims to understand the relationship between microglia activation and functional outcome after ischemic stroke in humans. The longitudinal ICARUS study involves serial TSPO- PET and MR imaging to uncover the characteristics of microglia activation in patients with cortical or sub-cortical lesions. Microglial activation will be correlated to inflammatory markers in blood and to stroke outcome. We hypothesise i) that a subpopulation of patients with acute stroke develop prominent microglial activation, ii) that patients with extensive microglial activation are more likely to have poor outcome and iii) that these patients will be more likely to benefit from immune interventions. The ongoing ICARUS study addresses the first two hypotheses and will prepare for a future immune intervention trial by developing criteria for the selection of suitable patients using TSPO PET. ICARUS will: (1) define the characteristics and determinants of microglial activation after human stroke; (2) correlate microglial activation with inflammatory markers in blood; (3) correlate microglial activation with infarct evolution, secondary neurodegeneration, and stroke outcome; and (4) develop criteria for patient selection for future immune intervention trials. To enable a direct comparison of microglial activation in human and experimental stroke we are further perform microglia-PET in three different experimental stroke models. This approach will validate specificity of the TSPO PET tracer signal by correlation with immunohistochemistry gold standard experiments. Furthermore, we will use a novel PET tracer targeting monoaminoxidase B in the experimental mouse models to explore the potential of this imaging biomarker for reactive astrocytosis in stroke.