Role of oxidative stress for neuro-vascular function

• Applicant: Professor Dr. Nikolaus Plesnila
• Subject Area: Molecular and Cellular Neurology and Neuropathology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 522474646

Reactive oxygen species (ROS) play a detrimental role upon reperfusion from cerebral ischemia, the current standard therapy for ischemic stroke. However, the exact vascular and cellular mechanisms of this "reperfusion injury" remain unknown mainly due to the lack of methodology to measure ROS in vivo and the lack of animal models that allow to investigate the controlled temporal and spatial induction of ROS. The current project will use novel chemogenetic technology to measure and induce ROS in a cell and organelle-specific manner in vitro and in vivo. These chemogenetic tools will be used in combination with in vivo 2-photon microscopy, single-cell transcriptomics, and a cell-based drug screening platform to 1) measure ROS in a mouse stroke model in cells of the neurovascular unit (NVU) to identify the cellular source of ROS production during reperfusion from cerebral ischemia, 2) to induce ROS production in the NVU of healthy animals to identify the specific role of ROS for neurovascular function, 3) to identify genes induced by cell-specific ROS production, and 4) to identify drugs which prevent or suppress ROS production. The results of the current project will identify the temporal and cellular profile of ROS production after cerebral ischemia, decipher the underlying gene expression, and identify effective antioxidative compounds thereby defining novel molecular and cellular targets and potential drugs for the treatment of stroke patients.

• DFG Programme: Research Grants
• International Connection: France, Turkey
• Cooperation Partners: Dr. Emrah Eroglu; Professor Pierre Gressens, Ph.D.