Great Expectations: The Promise of the Neurovascular Unit for Stroke Therapy

The concept of neurovascular unit highlights the vital interaction between the brain and its vessels and their coordinated response to injury. The cells constituting cerebral blood vessels, including endothelial cells, smooth muscle cells, pericytes, and perivascular cells, have an intimate spatial relationship with neurons and glia (astrocytes, microglia, oligodendroglia).  In the developing brain, vascular cells play a key role in the migration and differentiation of neural precursors. In the adult brain neurons and glia are functionally linked to cerebrovascular cells and work in concert to maintain the homeostasis of the neuronal microenvironment by regulating cerebral blood flow and blood-brain barrier permeability. Indeed, the brain is uniquely dependent on a continuous and well-regulated supply of blood flow to support its ever-changing energetic needs. Dysfunction of cerebral blood vessels is also observed early in the course of neurodegenerative diseases, implicating alterations in the neurovascular unit also in the mechanisms of neurodegeneration. Furthermore, after acute brain injury, neurons, glia and vascular cells react with a coordinated response that attempts to minimize neuronal damage while promoting tissue repair and reorganization. Increasing our limited understanding of how these cells work together to maintain brain health has profound implications for the pathobiology and treatment of neurovascular diseases, including stroke and dementia. Gaining such understanding will require a multidisciplinary approach that is best achieved by the synergistic interaction of international teams with complementary expertise. A multifaceted approach to unlock the inner workings of the neurovascular unit promises to have a transformative impact on the treatment of neurovascular brain disorders.