Project: Deciphering Cellular and Acellular Barrier Dysfunction in Cerebrovascular Diseases

Acronym	DeCoDis (Reference Number: NEURON_CV-100)
Project Topic	Most therapies of ischemic stroke have targeted reperfusion injury by blocking leukocyte or endothelial adhesion molecules known to be critical in peripheral inflammation, but with little success. However, no consideration has been given to the fact that malfunction of both cerebrovascular and meningeal brain barriers are a prerequisite for inflammation and edema. By combining the use of new mouse transgenic models, developed by consortium members, that for the first time permit visualization of the different cellular and acellular (basement membrane) constituents of the cerebrovascular and meningeal barriers, with targeted modulation of tissue resident, border associated macrophages (BAMs) versus infiltrating myeloid populations we will identify factors that stabilize these barriers or compromise them in cerebrovascular disease, with a focus on ischemic stroke. We propose that stabilization of brain barriers represents an as yet unexplored, but high potential, therapeutic option for cerebrovascular diseases. DeCoDis will close critical knowledge gaps on the contribution of barrier malfunction to the outcome of stroke and will identify the cellular and molecular underpinnings of brain barrier dysfunction and associated BAMs in stroke pathogenesis. It will, thereby, set the stage for exploring novel therapeutic approaches for the treatment of stroke by therapeutic stabilization of blood-brain barrier function.
Network	NEURON Cofund2
Call	Neuron Cofund2 Joint Call 2022

Project partner

Number	Name	Role	Country
1	Institute of Physiological Chemistry and Pathobiochemistry	Coordinator	Germany
2	Clinic for Neurology	Partner	Germany
3	Theodor Kocher Institute	Partner	Switzerland
4	Theodor Kocher Institute	Partner	Switzerland
5	CNRS UMR7280, INSERM U1104	Partner	France