Neurovascular unit

The neurovascular unit (NVU) comprises the components of the brain that collectively regulate cerebral blood flow in order to deliver the requisite nutrients to activated neurons.^[1] The NVU addresses the brain's unique dilemma of having high energy demands yet low energy storage capacity. In order to function properly, the brain must receive substrates for energy metabolism–mainly glucose–in specific areas, quantities, and times.^[2] Neurons do not have the same ability as, for example, muscle cells, which can use up their energy reserves and refill them later; therefore, cerebral metabolism must be driven in the moment. The neurovascular unit facilitates this ad hoc delivery and, thus, ensures that neuronal activity can continue seamlessly.^[2]

The neurovascular unit was formalized as a concept in 2001, at the inaugural Stroke Progress Review Group of the National Institute of Neurological Disorders and Stroke (NINDS).^[1] In prior years, the importance of both neurons and cerebral vasculature was well known; however, their interconnected relationship was not. The two were long considered distinct entities which, for the most part, operated independently. Since 2001, though, the rapid increase of scientific papers citing the neurovascular unit represents the growing understanding of the interactions that occur between the brain’s cells and blood vessels.^[1]

The neurovascular unit consists of neurons, astrocytes, vasculature (endothelial and vascular mural cells), the vasomotor apparatus (smooth muscle cells and pericytes), and microglia.^[1] Together these function in the homeostatic haemodynamic response of cerebral hyperaemia.^[3] Cerebral hyperaemia is a fundamental central nervous system mechanism of homeostasis that increases blood supply to neural tissue when necessary.^[3] This mechanism controls oxygen and nutrient levels using vasodilation and vasoconstriction in a multidimensional process involving the many cells of the neurovascular unit, along with multiple signaling molecules.^[1] The interactions between the components of the NVU allow it to sense neurons' needs of oxygen and glucose and, in turn, trigger the appropriate vasodilatory or vasoconstrictive responses.^[3] Thus, the NVU provides the architecture behind neurovascular coupling, which connects neuronal activity to cerebral blood flow and highlights the interdependence of their development, structure, and function.^[1]

The temporal and spatial link between cerebral blood flow and neuronal activity allows the former to serve as a proxy for the latter. Neuroimaging techniques that directly or indirectly monitor blood flow, such as fMRI and PET scans, can, thus, measure and locate activity in the brain with precision.^[1] Imaging of the brain also allows researchers to better understand the neurovascular unit and its many complexities. Furthermore, any impediments to the function of the neurovascular system will prevent neurons from receiving the appropriate nutrients. A complete stoppage for only a few minutes, which could be caused by arterial occlusion or heart failure, can result in permanent damage and death. Dysfunction in the NVU is also associated with neurodegenerative diseases including Alzheimer's and Huntington's disease.^[1]