Deep profiling of the immune response in the ischemic hemisphere in acute stroke

• Applicants: Dr. Mathias Gelderblom; Professor Dr. Immo Prinz
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology ; Molecular and Cellular Neurology and Neuropathology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 497674564

Animal data suggested that inflammation contributes to tissue damage in stroke. Since it is not possible to study the inflamed ischemic brain tissue in living patients, so far, these findings could only be correlated with the systemic immune response, non-invasive imaging data, and human postmortem tissue. To overcome this limitation and to directly investigate and quantify inflammation in human stroke, we set up an ethically approved protocol to aspirate ischemic blood from the acutely occluded middle cerebral artery distal to the thrombus during catheter-assisted thrombectomies. Simultaneously obtained blood from the carotid artery serves as a perfect matching control, which allows us to precisely determine the ischemia-induced immunologic changes behind the thrombus. By CITE-seq-assisted single cell RNA and TCR sequencing, these unique samples will enable an in-depth characterization of the local inflammatory response and migratory dynamics of leukocytes in the ischemic hemisphere. At the same time, we will employ single cell T cell receptor profiling to reveal the footprint of those T cell clones that have invaded the injured brain. To identify disease-driving molecular pathways in the ischemic immune response, the transcriptomic data of 50 patients sampled within 24 months will be integrated with three months post-stroke clinical outcome and imaging data.

• DFG Programme: Research Grants