Coordination Funds

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On a global level stroke represents the second leading cause of death and the primary cause of long-term disability among adults. In Germany one new stroke occurs every two minutes. Current treatment options for stroke are largely limited, and promising experimental findings often fail validation in clinical trials. Hence, new avenues of basic stroke research with high translation potential are desperately needed in order to successfully develop effective treatment strategies. The inflammatory response to ischemic brain injury has meanwhile been well established as a key pathomechanism contributing to stroke outcome. Stroke is traditionally not considered an inflammatory disease, yet it shares multiple features with (auto)immune brain disorders. While these neuroinflammatory mechanisms have been described in great detail for the acute phase after ischemic brain injury, mechanisms of brain-immune interaction during recovery in the chronic phase after stroke still await clarification. Likewise, consequences of immunomodulatory interventions for post-stroke repair and neuroplasticity are barely understood. Therefore, this Research Unit will focus on studying the role of neuroinflammation for tissue remodeling and long-term recovery following stroke. The projects put forward by this consortium are designed to i) address how immune cells—particularly microglia and T cells—influence the recovery process following stroke; ii) clarify the role of neuroinflammation in stroke patients in comparison to the mouse system; and iii) identify novel biomarkers of post-stroke neuroinflammation. Ultimately, our research consortium will address key questions regarding the rationale design of future immunomodulatory trials in stroke patients and will establish new standards for experimental, multicenter stroke research. These goals will be achieved in a joint effort and by using cutting-edge technologies including functional and imaging technologies and new treatment paradigms such as nanobodies in order to understand and to modulate the immune responses after stroke. Our goals will be realized by the close collaboration of internationally recognized experts from the fields of basic immunology, neuroimmunology, stroke immunology, and neurobiology together with clinical stroke researchers within this Research Unit. Importantly, all preclinical experiments will be highly standardized and SOPs will be implemented for the entire consortium. This will allow a novel degree of collaboration in which we will be enabled to exchange raw data across research projects and study sites. Key findings will be validated in multicenter preclinical randomized controlled trials (pRCT) in the second funding phase, and the translational relevance of our experimental data will be cross-validated by in-depth immune, imaging and clinical phenotyping of stroke patients.