The vascular neural network—a new paradigm in stroke pathophysiology

The neurovascular unit is a key concept in stroke medicine that for many years has been defined as the endothelial cells, neurons and glia surrounding cerebral capillaries. In this Perspectives article, the authors expand this concept to encompass more-distant circulation, smooth muscle cells and perivascular innervation. This 'neural vascular network' in turn points to new strategies for stroke therapy. The concept of the neurovascular unit as the key brain component affected by stroke is controversial, because current definitions of this entity neglect mechanisms that control perfusion and reperfusion of arteries and arterioles upstream of the cerebral microcirculation. Indeed, although definitions vary, many researchers consider the neurovascular unit to be restricted to endothelial cells, neurons and glia within millimetres of the cerebral capillary microcirculation. This Perspectives article highlights the roles of vascular smooth muscle, endothelial cells and perivascular innervation of cerebral arteries in the initiation and progression of, and recovery from, ischaemic stroke. The concept of the vascular neural network—which includes cerebral arteries, arterioles, and downstream neuronal and glial cell types and structures—is introduced as the fundamental component affected by stroke pathophysiology. The authors also propose that the vascular neural network should be considered the main target for future therapeutic intervention after cerebrovascular insult.