Accruing evidence indicates that glial cells play pivotal roles in maintaining multiple forms of metabolic coupling with neurons and the brain microvasculature. In particular, astrocytic end-feet functionally ensheathe most of the vascular network and serve as specialized exchange sites for ions and energy substrates with brain parenchyma. While in physiological conditions these functions contribute to neurovascular coupling, the precise sub-cellular changes occurring at the glio-vascular interface during brain injury are much less understood.

Building on preliminary data disclosing an important restructuring of the mitochondrial network in perivascular astrocytes reacting to brain injury, a major focus of this funding period has been that of investigating whether and how changes in astrocytic mitochondrial structure and metabolism play a role in tissue remodelling. The collected results revealed an unexpected role of mitochondria and associated organelles in controlling how perivascular astrocytic end-feet regulate angiogenesis and brain tissue repair (Figure 1), laying the ground for assessing and manipulating key metabolic signalling functions at the gliovascular interface.