"What happens in the small brain blood vessels and surrounding neurons and glia cells (the neurovascular unit) after a stroke? Can we therapeutically prevent this pathology to normalise blood flow regulation and improve outcome after stroke? These questions are at the heart of my proposal.Current treatment options for stroke - the leading cause of long-term disabilities in Europe - are remarkably limited. Numerous failed clinical trials suggest that merely neuroprotective drugs are insufficient. We must understand and treat pathological changes in the neurovascular unit as a whole.The study of molecular mechanisms governing the interaction between brain arterioles, neurons and glia cells (neurovascular coupling) has been halted by the lack of appropriate techniques. However, in recent years novel techniques have been developed, and an exciting research field is emerging – with the Nelson lab at University of Vermont as a front-runner. However, the novel techniques and knowledge have not yet been exploited to study neurovascular pathology in stroke – the main objective of my proposal.I will use advanced techniques in the Nelson lab to investigate alterations in a) neurovascular coupling in vivo, b) contractile function of small brain arterioles and c) intracellular calcium signals in these vessels and surrounding astrocytes after ischemic stroke in mice. I will then transfer key techniques to the return lab and use them together with quantitative mass spectrometry (proteomics) to test whether inhibition of a central intracellular signalling pathway activated in brain vessels after stroke can prevent pathology in the neurovascular unit and improve outcome.This will provide novel information on neurovascular coupling deficits in stroke and possible therapeutic targets. It will increase European excellence in neurovascular coupling by transferring frontier technical and scientific skills to Europe and fostering novel transatlantic collaborations."