PROJECT: JTC2022 - Cerebrovascular: MeniSPYs

The meninges have been described as an important cerebral invasion route in primary autoimmune diseases and also important in regulating cerebral blood flow, antigen drainage to the systemic immune compartment and recirculation of leukocytes from brain to blood. However, little is known about the role of meninges in ischemic stroke. Based on this knowledge, we postulate that a better understanding of the routes and mechanisms by which inflammatory cells invade the brain following stroke will open new avenues for stroke care. To address this issue, the present proposal utilizes a collaborative effort combining the latest tools in imaging, experimental models, cell- and tissue manipulation approaches and clinical research. We will focus on meningeal gateways to understand the key mechanisms controlling meningeal inflammation and inflammatory cell recruitment with particular emphasis on the role of meningeal inflammatory actions on unfavourable outcomes after stroke that could be therapeutically targeted for the benefit of patients. Our objectives are to: 1. Decipher the mechanisms leading to chronic post-stroke meningeal inflammation; 2. Validate these experimental findings in human meninges and CSF samples; 3. Determine the functional role of meningeal immunity on stroke outcome. .