PROJECT: JTC2022 - Cerebrovascular: VasOx

Role of oxidative stress for neuro-vascular function

Abstract

Reactive oxygen species (ROS) play a detrimental role upon reperfusion from cerebral ischemia, the current standard therapy for ischemic stroke. The exact vascular and cellular mechanisms of this "reperfusion injury", however, remains largely unknown due to the lack of methodology to measure ROS in vivo and the lack of animal models which allow the controlled temporal and spatial induction of ROS. The current project will use novel multicistronic chemogenetic technology to measure and induce ROS in a cell specific manner in vivo. These chemogenetic tools will be used in combination with in vivo 2-photon microscopy and single cell transcriptomics to 1) measure ROS in a mouse stroke model in cells of the neurovascular unit (NVU) in order to identify the cellular source of ROS production during reperfusion from cerebral ischemia, 2) to induce ROS production in the NVU of healthy animals in order to identify the specific role of ROS for neurovascular function and dysfunction, and 3) to identify genes induced by cell-specific ROS production. The results of the current project will identify the temporal and cellular profile of ROS production after cerebral ischemia and decipher the underlying gene expression thereby defining novel molecular and cellular targets for future precision medicine therapeutics for stroke patients.

Keywords

Omics approaches Imaging techniques Animal studies Development of new tools and/or technologies

Call topic

Cerebrovascular

Proposed runtime

n/a - n/a

Project team

Nikolaus Plesnila (Coordinator)
Germany (DFG)
Pierre Gessens
France (ANR)
Emrah Eroglu
Turkey (TUBITAK)